{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T17:00:46Z","timestamp":1792083646876,"version":"4.4.0"},"reference-count":297,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,7,13]],"date-time":"2022-07-13T00:00:00Z","timestamp":1657670400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council of Australia","doi-asserted-by":"publisher","award":["APP1037304"],"award-info":[{"award-number":["APP1037304"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council of Australia","doi-asserted-by":"publisher","award":["APP1158748"],"award-info":[{"award-number":["APP1158748"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The University of Queensland, Australia","award":["APP1037304"],"award-info":[{"award-number":["APP1037304"]}]},{"name":"The University of Queensland, Australia","award":["APP1158748"],"award-info":[{"award-number":["APP1158748"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Vaccines are one of the most significant medical interventions in the fight against infectious diseases. Since their discovery by Edward Jenner in 1796, vaccines have reduced the worldwide transmission to eradication levels of infectious diseases, including smallpox, diphtheria, hepatitis, malaria, and influenza. However, the complexity of developing safe and effective vaccines remains a barrier for combating many more infectious diseases. Immune stimulants (or adjuvants) are an indispensable factor in vaccine development, especially for inactivated and subunit-based vaccines due to their decreased immunogenicity compared to whole pathogen vaccines. Adjuvants are widely diverse in structure; however, their overall function in vaccine constructs is the same: to enhance and\/or prolong an immunological response. The potential for adverse effects as a result of adjuvant use, though, must be acknowledged and carefully managed. Understanding the specific mechanisms of adjuvant efficacy and safety is a key prerequisite for adjuvant use in vaccination. Therefore, rigorous pre-clinical and clinical research into adjuvant development is essential. Overall, the incorporation of adjuvants allows for greater opportunities in advancing vaccine development and the importance of immune stimulants drives the emergence of novel and more effective adjuvants. This article highlights recent advances in vaccine adjuvant development and provides detailed data from pre-clinical and clinical studies specific to infectious diseases. Future perspectives into vaccine adjuvant development are also highlighted.<\/jats:p>","DOI":"10.3390\/vaccines10071120","type":"journal-article","created":{"date-parts":[[2022,7,14]],"date-time":"2022-07-14T00:12:40Z","timestamp":1657757560000},"page":"1120","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":102,"title":["Advances in Infectious Disease Vaccine Adjuvants"],"prefix":"10.3390","volume":"10","author":[{"given":"Jingyi","family":"Fan","sequence":"first","affiliation":[{"name":"School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8108-4626","authenticated-orcid":false,"given":"Shengbin","family":"Jin","sequence":"additional","affiliation":[{"name":"School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lachlan","family":"Gilmartin","sequence":"additional","affiliation":[{"name":"School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Istvan","family":"Toth","sequence":"additional","affiliation":[{"name":"School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD 4072, Australia"},{"name":"Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4072, Australia"},{"name":"School of Pharmacy, The University of Queensland, Woolloongabba, QLD 4102, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5392-1880","authenticated-orcid":false,"given":"Waleed","family":"Hussein","sequence":"additional","affiliation":[{"name":"School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6424-7502","authenticated-orcid":false,"given":"Rachel","family":"Stephenson","sequence":"additional","affiliation":[{"name":"School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1038\/s41579-021-00639-z","article-title":"Infectious disease in an era of global change","volume":"20","author":"Baker","year":"2022","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1128\/CMR.17.1.235-254.2004","article-title":"History, dynamics, and public health importance of malaria parasite resistance","volume":"17","author":"Talisuna","year":"2004","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1722","DOI":"10.3389\/fimmu.2019.01722","article-title":"Vaccine Evolution and Its Application to Fight Modern Threats","volume":"10","author":"Andreano","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1016\/S0091-6749(03)02017-7","article-title":"Prometheus in Gloucestershire: Edward Jenner, 1749-1823","volume":"112","author":"Dworetzky","year":"2003","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Azuar, A., Jin, W., Mukaida, S., Hussein, W.M., Toth, I., and Skwarczynski, M. (2019). Recent advances in the development of peptide vaccines and their delivery systems against Group A Streptococcus. Vaccines, 7.","DOI":"10.3390\/vaccines7030058"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"20130433","DOI":"10.1098\/rstb.2013.0433","article-title":"The contribution of vaccination to global health: Past, present and future","volume":"369","author":"Greenwood","year":"2014","journal-title":"Philos. Trans. R. Soc. B Biol. Sci."},{"key":"ref_7","unstructured":"Kastin, A.J. (2013). Handbook of Biologically Active Peptides, Academic Press\/Elsevier."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"S5","DOI":"10.1038\/nm1209","article-title":"Vaccines: Past, present and future","volume":"11","author":"Plotkin","year":"2005","journal-title":"Nat. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1038\/nrmicro1688","article-title":"The contribution of immunology to the rational design of novel antibacterial vaccines","volume":"5","author":"Kaufmann","year":"2007","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1002\/cmdc.201200487","article-title":"Modern subunit vaccines: Development, components, and research opportunities","volume":"8","author":"Moyle","year":"2013","journal-title":"ChemMedChem"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bcp.2016.05.001","article-title":"Vaccine technologies: From whole organisms to rationally designed protein assemblies","volume":"120","author":"Karch","year":"2016","journal-title":"Biochem. Pharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"654","DOI":"10.3390\/vaccines2030654","article-title":"Schistosome Vaccine Adjuvants in Preclinical and Clinical Research","volume":"2","author":"Stephenson","year":"2014","journal-title":"Vaccines"},{"key":"ref_13","first-page":"1459394","article-title":"Adjuvants: Classification, Modus Operandi, and Licensing","volume":"2016","author":"Lunardelli","year":"2016","journal-title":"J. Immunol. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.1038\/nm.3409","article-title":"Key roles of adjuvants in modern vaccines","volume":"19","author":"Reed","year":"2013","journal-title":"Nat. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"54","DOI":"10.7774\/cevr.2015.4.1.54","article-title":"Vaccine adjuvant materials for cancer immunotherapy and control of infectious disease","volume":"4","author":"Lim","year":"2015","journal-title":"Clin. Exp. Vaccine Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1038\/s41577-018-0029-z","article-title":"IFNgamma: Signalling, epigenetics and roles in immunity, metabolism, disease and cancer immunotherapy","volume":"18","author":"Ivashkiv","year":"2018","journal-title":"Nat. Rev. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"425","DOI":"10.3389\/fcimb.2020.00425","article-title":"Dynamic Natural Killer Cell and T Cell Responses to Influenza Infection","volume":"10","author":"Frank","year":"2020","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/j.cyto.2015.02.007","article-title":"B cells responses and cytokine production are regulated by their immune microenvironment","volume":"74","author":"Vazquez","year":"2015","journal-title":"Cytokine"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1186\/s13223-018-0278-1","article-title":"An introduction to immunology and immunopathology","volume":"14","author":"Marshall","year":"2018","journal-title":"Allergy Asthma Clin. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"811","DOI":"10.3389\/fimmu.2019.00811","article-title":"Understanding Fc Receptor Involvement in Inflammatory Diseases: From Mechanisms to New Therapeutic Tools","volume":"10","author":"Benhamou","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"544","DOI":"10.3389\/fimmu.2019.00544","article-title":"Inside-Out Control of Fc-Receptors","volume":"10","author":"Koenderman","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1002\/med.21553","article-title":"Recent clinical trends in Toll-like receptor targeting therapeutics","volume":"39","author":"Anwar","year":"2019","journal-title":"Med. Res. Rev."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1097\/PPO.0b013e3181eaca65","article-title":"Toll-like receptor agonists: Are they good adjuvants?","volume":"16","author":"Gnjatic","year":"2010","journal-title":"Cancer J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.intimp.2018.03.002","article-title":"Toll-like receptors in immunity and inflammatory diseases: Past, present, and future","volume":"59","author":"Vijay","year":"2018","journal-title":"Int. Immunopharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e85","DOI":"10.1038\/cti.2016.22","article-title":"Toll-like receptors: The swiss army knife of immunity and vaccine development","volume":"5","author":"Dowling","year":"2016","journal-title":"Clin. Transl. Immunology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.2174\/138161210790963779","article-title":"Toll-like receptors: Cost or benefit for cancer?","volume":"16","author":"Matijevic","year":"2010","journal-title":"Curr. Pharm Des."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1038\/nrd3203","article-title":"Targeting Toll-like receptors: Emerging therapeutics?","volume":"9","author":"Hennessy","year":"2010","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Jeong, S.K., Heo, Y.K., Jeong, J.H., Ham, S.J., Yum, J.S., Ahn, B.C., Song, C.S., and Chun, E.Y. (2021). COVID-19 Subunit Vaccine with a Combination of TLR1\/2 and TLR3 Agonists Induces Robust and Protective Immunity. Vaccines, 9.","DOI":"10.3390\/vaccines9090957"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1080\/08923970902802926","article-title":"The potential use of Toll-like receptor (TLR) agonists and antagonists as prophylactic and\/or therapeutic agents","volume":"31","author":"Makkouk","year":"2009","journal-title":"Immunopharmacol. Immunotoxicol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/S0264-410X(96)00183-1","article-title":"Adjuvants\u2014A classification and review of their modes of action","volume":"15","author":"Cox","year":"1997","journal-title":"Vaccine"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1038\/s41541-018-0089-x","article-title":"Optimizing the utilization of aluminum adjuvants in vaccines: You might just get what you want","volume":"3","author":"HogenEsch","year":"2018","journal-title":"NPJ. Vaccines"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"23","DOI":"10.7774\/cevr.2015.4.1.23","article-title":"Polyionic vaccine adjuvants: Another look at aluminum salts and polyelectrolytes","volume":"4","author":"Powell","year":"2015","journal-title":"Clin. Exp. Vaccine Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"5496","DOI":"10.1039\/C6TB01131D","article-title":"Nanomaterial-Based Vaccine Adjuvants","volume":"4","author":"Sun","year":"2016","journal-title":"J. Mater. Chem. B"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3167","DOI":"10.1016\/j.vaccine.2019.04.055","article-title":"Vaccine adjuvants: Understanding the structure and mechanism of adjuvanticity","volume":"37","author":"Shi","year":"2019","journal-title":"Vaccine"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1177\/2051013613480144","article-title":"Working together: Interactions between vaccine antigens and adjuvants","volume":"1","author":"Fox","year":"2013","journal-title":"Ther. Adv. Vaccines"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"114","DOI":"10.3389\/fimmu.2013.00114","article-title":"Mechanisms of action of adjuvants","volume":"4","author":"Awate","year":"2013","journal-title":"Front. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Hogenesch, H. (2013). Mechanism of immunopotentiation and safety of aluminum adjuvants. Front. Immunol., 3.","DOI":"10.3389\/fimmu.2012.00406"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1126\/science.abc1932","article-title":"Development of an inactivated vaccine candidate for SARS-CoV-2","volume":"369","author":"Gao","year":"2020","journal-title":"Science"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1093\/infdis\/jiw453","article-title":"A Randomized, Controlled, Observer-Blinded Phase 1 Study of the Safety and Immunogenicity of a Respiratory Syncytial Virus Vaccine with or Without Alum Adjuvant","volume":"215","author":"Langley","year":"2017","journal-title":"J. Infect. Dis."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"4073","DOI":"10.7150\/ijbs.64762","article-title":"Respiratory syncytial virus: From pathogenesis to potential therapeutic strategies","volume":"17","author":"Shang","year":"2021","journal-title":"Int. J. Biol. Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1097\/INF.0000000000001124","article-title":"A Phase 2, Randomized, Active-controlled, Observer-blinded Study to Assess the Immunogenicity, Tolerability and Safety of Bivalent rLP2086, a Meningococcal Serogroup B Vaccine, Coadministered With Tetanus, Diphtheria and Acellular Pertussis Vaccine and Serogroup A, C, Y and W-135 Meningococcal Conjugate Vaccine in Healthy US Adolescents","volume":"35","author":"Muse","year":"2016","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1093\/infdis\/jiv406","article-title":"A Randomized, Blinded, Controlled, Dose-Ranging Study of a Respiratory Syncytial Virus Recombinant Fusion (F) Nanoparticle Vaccine in Healthy Women of Childbearing Age","volume":"213","author":"Glenn","year":"2016","journal-title":"J. Infect. Dis."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1661","DOI":"10.1086\/508748","article-title":"Randomized, double-blind, placebo-controlled efficacy trial of a bivalent recombinant glycoprotein 120 HIV-1 vaccine among injection drug users in Bangkok, Thailand","volume":"194","author":"Pitisuttithum","year":"2006","journal-title":"J. Infect. Dis."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1016\/S0140-6736(21)00241-5","article-title":"Safety and immunogenicity of S-Trimer (SCB-2019), a protein subunit vaccine candidate for COVID-19 in healthy adults: A phase 1, randomised, double-blind, placebo-controlled trial","volume":"397","author":"Richmond","year":"2021","journal-title":"Lancet"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1128\/CDLI.7.6.899-903.2000","article-title":"Calcium phosphate nanoparticle adjuvant","volume":"7","author":"He","year":"2000","journal-title":"Clin. Diagn. Lab. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1080\/14760584.2017.1355733","article-title":"Calcium phosphate nanoparticles as a new generation vaccine adjuvant","volume":"16","author":"Lin","year":"2017","journal-title":"Expert Rev. Vaccines"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"88","DOI":"10.7774\/cevr.2015.4.1.88","article-title":"Systemic antibody response to nano-size calcium phospate biocompatible adjuvant adsorbed HEV-71 killed vaccine","volume":"4","author":"Saeed","year":"2015","journal-title":"Clin. Exp. Vaccine Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1016\/j.rvsc.2010.09.008","article-title":"Calcium phosphate coupled Newcastle disease vaccine elicits humoral and cell mediated immune responses in chickens","volume":"91","author":"Koppad","year":"2011","journal-title":"Res. Vet. Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.vetmic.2009.05.004","article-title":"Calcium phosphate nanoparticle prepared with foot and mouth disease virus P1-3CD gene construct protects mice and guinea pigs against the challenge virus","volume":"139","author":"Joyappa","year":"2009","journal-title":"Vet. Microbiol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"5145","DOI":"10.1016\/j.vaccine.2011.05.041","article-title":"Safety and immunogenicity of a recombinant M2e-flagellin influenza vaccine (STF2.4xM2e) in healthy adults","volume":"29","author":"Turley","year":"2011","journal-title":"Vaccine"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"8268","DOI":"10.1016\/j.vaccine.2010.10.009","article-title":"Safety and immunogenicity of a recombinant hemagglutinin influenza-flagellin fusion vaccine (VAX125) in healthy young adults","volume":"28","author":"Treanor","year":"2010","journal-title":"Vaccine"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"4897","DOI":"10.1016\/j.vaccine.2011.05.001","article-title":"Induction of a potent immune response in the elderly using the TLR-5 agonist, flagellin, with a recombinant hemagglutinin influenza-flagellin fusion vaccine (VAX125, STF2.HA1 SI)","volume":"29","author":"Taylor","year":"2011","journal-title":"Vaccine"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"ofw015","DOI":"10.1093\/ofid\/ofw015","article-title":"Phase 1 Safety and Immunogenicity Study of a Quadrivalent Seasonal Flu Vaccine Comprising Recombinant Hemagglutinin-Flagellin Fusion Proteins","volume":"3","author":"Tussey","year":"2016","journal-title":"Open Forum Infect. Dis."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1080\/14760584.2018.1457443","article-title":"Flagellin as a vaccine adjuvant","volume":"17","author":"Cui","year":"2018","journal-title":"Expert Rev. Vaccines"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"eaas9930","DOI":"10.1126\/sciadv.aas9930","article-title":"The adjuvant GLA-AF enhances human intradermal vaccine responses","volume":"4","author":"Carter","year":"2018","journal-title":"Sci. Adv."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1007\/s00436-015-4316-3","article-title":"Protective immunity against Naegleria fowleri infection on mice immunized with the rNfa1 protein using mucosal adjuvants","volume":"114","author":"Lee","year":"2015","journal-title":"Parasitol. Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3773","DOI":"10.1128\/IAI.00306-10","article-title":"Plasmodium vivax ookinete surface protein Pvs25 linked to cholera toxin B subunit induces potent transmission-blocking immunity by intranasal as well as subcutaneous immunization","volume":"78","author":"Miyata","year":"2010","journal-title":"Infect. Immun."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Maeto, C., Rodriguez, A.M., Holgado, M.P., Falivene, J., and Gherardi, M.M. (2014). Novel mucosal DNA-MVA HIV vaccination in which DNA-IL-12 plus cholera toxin B subunit (CTB) cooperates to enhance cellular systemic and mucosal genital tract immunity. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0107524"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1038\/s41586-019-1817-8","article-title":"Prevention of tuberculosis in macaques after intravenous BCG immunization","volume":"577","author":"Darrah","year":"2020","journal-title":"Nature"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1056\/NEJMoa1714021","article-title":"Prevention of M. tuberculosis Infection with H4:IC31 Vaccine or BCG Revaccination","volume":"379","author":"Nemes","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"100313","DOI":"10.1016\/j.eclinm.2020.100313","article-title":"A phase 1b randomized study of the safety and immunological responses to vaccination with H4:IC31, H56:IC31, and BCG revaccination in Mycobacterium tuberculosis-uninfected adolescents in Cape Town, South Africa","volume":"21","author":"Bekker","year":"2020","journal-title":"EClinicalMedicine"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1038\/s41585-021-00481-1","article-title":"100 years of Bacillus Calmette-Guerin immunotherapy: From cattle to COVID-19","volume":"18","author":"Lobo","year":"2021","journal-title":"Nat. Rev. Urol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"17720","DOI":"10.1073\/pnas.2008410117","article-title":"BCG vaccine protection from severe coronavirus disease 2019 (COVID-19)","volume":"117","author":"Escobar","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1097\/00042560-199604010-00005","article-title":"Initial studies on active immunization of HIV-infected subjects using a gp120-depleted HIV-1 Immunogen: Long-term follow-up","volume":"11","author":"Levine","year":"1996","journal-title":"J. Acquir. Immune Defic. Syndr. Hum. Retrovirol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1998","DOI":"10.1016\/S0140-6736(20)31048-5","article-title":"Safety and immunogenicity of a mosquito saliva peptide-based vaccine: A randomised, placebo-controlled, double-blind, phase 1 trial","volume":"395","author":"Manning","year":"2020","journal-title":"Lancet"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"S10","DOI":"10.1016\/j.ijid.2019.03.020","article-title":"Cumulative clinical experience with MF59-adjuvanted trivalent seasonal influenza vaccine in young children and adults 65 years of age and older","volume":"85","author":"Lindert","year":"2019","journal-title":"Int. J. Infect. Dis."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1016\/S1473-3099(21)00200-0","article-title":"Safety and immunogenicity of an MF59-adjuvanted spike glycoprotein-clamp vaccine for SARS-CoV-2: A randomised, double-blind, placebo-controlled, phase 1 trial","volume":"21","author":"Chappell","year":"2021","journal-title":"Lancet Infect. Dis."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"218","DOI":"10.3389\/fimmu.2015.00218","article-title":"Development of the Brazilian Anti Schistosomiasis Vaccine Based on the Recombinant Fatty Acid Binding Protein Sm14 Plus GLA-SE Adjuvant","volume":"6","author":"Tendler","year":"2015","journal-title":"Front. Immunol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1038\/s41541-018-0057-5","article-title":"The TLR-4 agonist adjuvant, GLA-SE, improves magnitude and quality of immune responses elicited by the ID93 tuberculosis vaccine: First-in-human trial","volume":"3","author":"Coler","year":"2018","journal-title":"NPJ. Vaccines"},{"key":"ref_70","first-page":"145","article-title":"Enhancement of Th1 immune responses to recombinant influenza nucleoprotein by Ribi adjuvant","volume":"36","author":"Cargnelutti","year":"2013","journal-title":"New Microbiol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1007\/s00430-001-0104-z","article-title":"The immunogenicity of Mycobacterium paratuberculosis 85B antigen","volume":"190","author":"Mullerad","year":"2002","journal-title":"Med. Microbiol. Immunol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"100361","DOI":"10.1016\/j.jhepr.2021.100361","article-title":"Therapeutic vaccine BRII-179 restores HBV-specific immune responses in patients with chronic HBV in a phase Ib\/IIa study","volume":"3","author":"Ma","year":"2021","journal-title":"JHEP Rep."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Brekke, K., Sommerfelt, M., Okvist, M., Dyrhol-Riise, A.M., and Kvale, D. (2017). The therapeutic HIV Env C5\/gp41 vaccine candidate Vacc-C5 induces specific T cell regulation in a phase I\/II clinical study. BMC Infect. Dis., 17.","DOI":"10.1186\/s12879-017-2316-x"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.cytogfr.2021.01.001","article-title":"Granulocyte macrophage colony-stimulating factor has come of age: From a vaccine adjuvant to antiviral immunotherapy","volume":"59","author":"Petrina","year":"2021","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"4073","DOI":"10.1016\/j.vaccine.2008.05.035","article-title":"Effect of sublingual administration of interferon-alpha on the immune response to influenza vaccination in institutionalized elderly individuals","volume":"26","author":"Launay","year":"2008","journal-title":"Vaccine"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1016\/j.imbio.2017.12.001","article-title":"Applications of chemokines as adjuvants for vaccine immunotherapy","volume":"223","author":"Mohan","year":"2018","journal-title":"Immunobiology"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"555","DOI":"10.4049\/jimmunol.1600497","article-title":"A Novel R848-Conjugated Inactivated Influenza Virus Vaccine Is Efficacious and Safe in a Neonate Nonhuman Primate Model","volume":"197","author":"Holbrook","year":"2016","journal-title":"J. Immunol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1016\/j.biomaterials.2018.03.026","article-title":"Potent anti-viral vaccine adjuvant based on pH-degradable nanogels with covalently linked small molecule imidazoquinoline TLR7\/8 agonist","volume":"178","author":"Nuhn","year":"2018","journal-title":"Biomaterials"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"4205","DOI":"10.1016\/j.vaccine.2016.06.056","article-title":"A phase III clinical study to compare the immunogenicity and safety of the 9-valent and quadrivalent HPV vaccines in men","volume":"34","author":"Meijer","year":"2016","journal-title":"Vaccine"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1001\/jama.2020.2477","article-title":"Effect of a Chikungunya Virus-Like Particle Vaccine on Safety and Tolerability Outcomes: A Randomized Clinical Trial","volume":"323","author":"Chen","year":"2020","journal-title":"JAMA"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"2346","DOI":"10.1056\/NEJMc1803554","article-title":"Improved Titers against Influenza Drift Variants with a Nanoparticle Vaccine","volume":"378","author":"Shinde","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1016\/j.ijbiomac.2021.04.005","article-title":"Virosome-based nanovaccines; a promising bioinspiration and biomimetic approach for preventing viral diseases: A review","volume":"182","author":"Asadi","year":"2021","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Thompson, F.M., Porter, D.W., Okitsu, S.L., Westerfeld, N., Vogel, D., Todryk, S., Poulton, I., Correa, S., Hutchings, C., and Berthoud, T. (2008). Evidence of blood stage efficacy with a virosomal malaria vaccine in a phase IIa clinical trial. PLoS ONE, 3.","DOI":"10.1371\/journal.pone.0001493"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"5490","DOI":"10.1016\/j.vaccine.2014.07.078","article-title":"Intranasal seasonal influenza vaccine and a TLR-3 agonist, rintatolimod, induced cross-reactive IgA antibody formation against avian H5N1 and H7N9 influenza HA in humans","volume":"32","author":"Overton","year":"2014","journal-title":"Vaccine"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"725","DOI":"10.3389\/fimmu.2019.00725","article-title":"Poly-ICLC, a TLR3 Agonist, Induces Transient Innate Immune Responses in Patients with Treated HIV-Infection: A Randomized Double-Blinded Placebo Controlled Trial","volume":"10","author":"Saxena","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"6377","DOI":"10.1016\/j.vaccine.2014.06.065","article-title":"Clinical evaluation of CpG oligonucleotides as adjuvants for vaccines targeting infectious diseases and cancer","volume":"32","author":"Scheiermann","year":"2014","journal-title":"Vaccine"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Mullen, G.E., Ellis, R.D., Miura, K., Malkin, E., Nolan, C., Hay, M., Fay, M.P., Saul, A., Zhu, D., and Rausch, K. (2008). Phase 1 trial of AMA1-C1\/Alhydrogel plus CPG 7909: An asexual blood-stage vaccine for Plasmodium falciparum malaria. PLoS ONE, 3.","DOI":"10.1371\/journal.pone.0002940"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1652","DOI":"10.1016\/j.vaccine.2017.01.055","article-title":"Safety and immunogenicity of the novel H4:IC31 tuberculosis vaccine candidate in BCG-vaccinated adults: Two phase I dose escalation trials","volume":"35","author":"Norrby","year":"2017","journal-title":"Vaccine"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1920","DOI":"10.1056\/NEJMoa2022483","article-title":"An mRNA Vaccine against SARS-CoV-2\u2014Preliminary Report","volume":"383","author":"Jackson","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"7098","DOI":"10.1016\/j.vaccine.2014.10.036","article-title":"A novel liposomal adjuvant system, CAF01, promotes long-lived Mycobacterium tuberculosis-specific T-cell responses in human","volume":"32","author":"Joosten","year":"2014","journal-title":"Vaccine"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1016\/S1473-3099(19)30279-8","article-title":"Safety and immunogenicity of the chlamydia vaccine candidate CTH522 adjuvanted with CAF01 liposomes or aluminium hydroxide: A first-in-human, randomised, double-blind, placebo-controlled, phase 1 trial","volume":"19","author":"Abraham","year":"2019","journal-title":"Lancet Infect. Dis."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"2178","DOI":"10.1056\/NEJMoa1101245","article-title":"Norovirus vaccine against experimental human Norwalk Virus illness","volume":"365","author":"Atmar","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"6469","DOI":"10.1016\/j.vaccine.2014.09.034","article-title":"Immunogenicity and safety of Advax, a novel polysaccharide adjuvant based on delta inulin, when formulated with hepatitis B surface antigen: A randomized controlled Phase 1 study","volume":"32","author":"Gordon","year":"2014","journal-title":"Vaccine"},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Vasan, S., Schlesinger, S.J., Huang, Y., Hurley, A., Lombardo, A., Chen, Z., Than, S., Adesanya, P., Bunce, C., and Boaz, M. (2010). Phase 1 safety and immunogenicity evaluation of ADVAX, a multigenic, DNA-based clade C\/B\u2019 HIV-1 candidate vaccine. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0008617"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"5284","DOI":"10.1016\/j.vaccine.2009.05.028","article-title":"Dendritic cells loaded with HIV-1 p24 proteins adsorbed on surfactant-free anionic PLA nanoparticles induce enhanced cellular immune responses against HIV-1 after vaccination","volume":"27","author":"Aline","year":"2009","journal-title":"Vaccine"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"809","DOI":"10.3851\/IMP1295","article-title":"Alpha-galactosylceramide in chronic hepatitis B infection: Results from a randomized placebo-controlled Phase I\/II trial","volume":"14","author":"Woltman","year":"2009","journal-title":"Antivir. Ther."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"7892","DOI":"10.1016\/j.vaccine.2020.10.064","article-title":"NVX-CoV2373 vaccine protects cynomolgus macaque upper and lower airways against SARS-CoV-2 challenge","volume":"38","author":"Patel","year":"2020","journal-title":"Vaccine"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1172","DOI":"10.1056\/NEJMoa2107659","article-title":"Safety and Efficacy of NVX-CoV2373 COVID-19 Vaccine","volume":"385","author":"Heath","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"3953","DOI":"10.1016\/j.vaccine.2015.06.047","article-title":"ISCOMATRIX adjuvant promotes epitope spreading and antibody affinity maturation of influenza A H7N9 virus like particle vaccine that correlate with virus neutralization in humans","volume":"33","author":"Chung","year":"2015","journal-title":"Vaccine"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1645\/GE-3186.1","article-title":"Vaccine-induced protection against murine schistosomiasis mansoni with larval excretory-secretory antigens and papain or type-2 cytokines","volume":"99","author":"Tallima","year":"2013","journal-title":"J. Parasitol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1863","DOI":"10.1056\/NEJMoa1102287","article-title":"First results of phase 3 trial of RTS,S\/AS01 malaria vaccine in African children","volume":"365","author":"Rts","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2546","DOI":"10.1016\/j.vaccine.2016.04.019","article-title":"Strain-specific Plasmodium falciparum multifunctional CD4+ T cell cytokine expression in Malian children immunized with the FMP2.1\/AS02A vaccine candidate","volume":"34","author":"Graves","year":"2016","journal-title":"Vaccine"},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Francica, J.R., Flynn, B.J., Foulds, K.E., Noe, A.T., Werner, A.P., Moore, I.N., Gagne, M., Johnston, T.S., Tucker, C., and Davis, R.L. (2021). Vaccination with SARS-CoV-2 Spike Protein and AS03 Adjuvant Induces Rapid Anamnestic Antibodies in the Lung and Protects Against Virus Challenge in Nonhuman Primates. bioRxiv.","DOI":"10.1101\/2021.03.02.433390"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1038\/s41586-021-03530-2","article-title":"Adjuvanting a subunit COVID-19 vaccine to induce protective immunity","volume":"594","author":"Arunachalam","year":"2021","journal-title":"Nature"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"4246","DOI":"10.1016\/j.vaccine.2019.06.039","article-title":"An indirect comparison meta-analysis of AS03 and MF59 adjuvants in pandemic influenza A(H1N1)pdm09 vaccines","volume":"37","author":"Hauser","year":"2019","journal-title":"Vaccine"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"2378","DOI":"10.1016\/j.vaccine.2008.02.068","article-title":"Safety and reactogenicity profile of an adjuvanted H5N1 pandemic candidate vaccine in adults within a phase III safety trial","volume":"26","author":"Rumke","year":"2008","journal-title":"Vaccine"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1576","DOI":"10.1093\/infdis\/jiaa561","article-title":"Efficacy of AS04-Adjuvanted Vaccine Against Human Papillomavirus (HPV) Types 16 and 18 in Clearing Incident HPV Infections: Pooled Analysis of Data From the Costa Rica Vaccine Trial and the PATRICIA Study","volume":"223","author":"Tota","year":"2021","journal-title":"J. Infect. Dis."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/S0169-409X(98)00008-8","article-title":"Aluminum compounds as vaccine adjuvants","volume":"32","author":"Gupta","year":"1998","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"18185","DOI":"10.1021\/acsomega.0c01792","article-title":"Enhanced Oral Vaccine Efficacy of Polysaccharide-Coated Calcium Phosphate Nanoparticles","volume":"5","author":"Cao","year":"2020","journal-title":"ACS Omega"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"51","DOI":"10.4110\/in.2015.15.2.51","article-title":"Recent advances of vaccine adjuvants for infectious diseases","volume":"15","author":"Lee","year":"2015","journal-title":"Immune Netw."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1021\/acs.jproteome.9b00517","article-title":"Metabolic Profiling and Compound-Class Identification Reveal Alterations in Serum Triglyceride Levels in Mice Immunized with Human Vaccine Adjuvant Alum","volume":"19","author":"Khoomrung","year":"2020","journal-title":"J. Proteome Res."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1002\/eji.201747150","article-title":"The vaccine adjuvant alum promotes IL-10 production that suppresses Th1 responses","volume":"48","author":"Oleszycka","year":"2018","journal-title":"Eur. J. Immunol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1007\/s40264-015-0350-4","article-title":"Comparative safety of vaccine adjuvants: A summary of current evidence and future needs","volume":"38","author":"Petrovsky","year":"2015","journal-title":"Drug Saf."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1186\/s12977-018-0445-y","article-title":"Stabilizing HIV-1 envelope glycoprotein trimers to induce neutralizing antibodies","volume":"15","author":"Sanders","year":"2018","journal-title":"Retrovirology"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"2264","DOI":"10.1016\/j.xphs.2019.01.033","article-title":"Developability assessment of physicochemical properties and stability profiles of HIV-1 BG505 SOSIP.664 and BG505 SOSIP.v4.1-GT1.1 gp140 envelope glycoprotein trimers as candidate vaccine antigens","volume":"108","author":"Whitaker","year":"2019","journal-title":"J. Pharm. Sci."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1089\/aid.2019.0239","article-title":"A Systematic Approach to HIV-1 Vaccine Immunogen Selection","volume":"36","author":"Bontempo","year":"2020","journal-title":"AIDS Res. Hum. Retrovir."},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Sanders, R.W., Derking, R., Cupo, A., Julien, J.P., Yasmeen, A., de Val, N., Kim, H.J., Blattner, C., de la Pena, A.T., and Korzun, J. (2013). A next-generation cleaved, soluble HIV-1 Env trimer, BG505 SOSIP.664 gp140, expresses multiple epitopes for broadly neutralizing but not non-neutralizing antibodies. PLoS Pathog., 9.","DOI":"10.1371\/journal.ppat.1003618"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"106054","DOI":"10.1016\/j.ijantimicag.2020.106054","article-title":"Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2): A global pandemic and treatment strategies","volume":"56","author":"Sharma","year":"2020","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1126\/science.abb2507","article-title":"Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation","volume":"367","author":"Wrapp","year":"2020","journal-title":"Science"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1038\/s41577-020-00480-0","article-title":"Viral targets for vaccines against COVID-19","volume":"21","author":"Dai","year":"2021","journal-title":"Nat. Rev. Immunol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1038\/s41573-021-00163-y","article-title":"Emerging concepts in the science of vaccine adjuvants","volume":"20","author":"Pulendran","year":"2021","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1038\/nri2510","article-title":"Towards an understanding of the adjuvant action of aluminium","volume":"9","author":"Marrack","year":"2009","journal-title":"Nat. Rev. Immunol."},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Singh, N., and Tscharke, D.C. (2020). Herpes Simplex Virus Latency Is Noisier the Closer We Look. J. Virol., 94.","DOI":"10.1128\/JVI.01701-19"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1096\/fj.12-218362","article-title":"Iron oxide nanoparticles as a clinically acceptable delivery platform for a recombinant blood-stage human malaria vaccine","volume":"27","author":"Pusic","year":"2013","journal-title":"FASEB J."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"e373","DOI":"10.1038\/emm.2017.172","article-title":"Bacterial flagellin-a potent immunomodulatory agent","volume":"49","author":"Hajam","year":"2017","journal-title":"Exp. Mol. Med."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1006\/jmbi.2001.4597","article-title":"Flagellin polymerisation control by a cytosolic export chaperone","volume":"308","author":"Auvray","year":"2001","journal-title":"J. Mol. Biol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/1742-4933-4-9","article-title":"Challenges for vaccination in the elderly","volume":"4","author":"Aspinall","year":"2007","journal-title":"Immun. Ageing"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1128\/CVI.00333-08","article-title":"Flagellin-F1-V fusion protein is an effective plague vaccine in mice and two species of nonhuman primates","volume":"16","author":"Mizel","year":"2009","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"3317","DOI":"10.1128\/IAI.01150-12","article-title":"Adjuvant activity of naturally occurring monophosphoryl lipopolysaccharide preparations from mucosa-associated bacteria","volume":"81","author":"Chilton","year":"2013","journal-title":"Infect. Immun."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1586\/14760584.2015.1026808","article-title":"Biosynthetically engineered lipopolysaccharide as vaccine adjuvant","volume":"14","author":"Zariri","year":"2015","journal-title":"Expert Rev. Vaccines"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1165\/rcmb.2008-0152OC","article-title":"Myeloid differentiation protein-2-dependent and -independent neutrophil accumulation during Escherichia coli pneumonia","volume":"40","author":"Cai","year":"2009","journal-title":"Am. J. Respir. Cell. Mol. Biol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"1628","DOI":"10.1126\/science.1138963","article-title":"The vaccine adjuvant monophosphoryl lipid A as a TRIF-biased agonist of TLR4","volume":"316","author":"Cekic","year":"2007","journal-title":"Science"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"577823","DOI":"10.3389\/fimmu.2020.577823","article-title":"MPL Adjuvant Contains Competitive Antagonists of Human TLR4","volume":"11","author":"Wang","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"3231","DOI":"10.1007\/s00018-008-8228-6","article-title":"Putting endotoxin to work for us: Monophosphoryl lipid A as a safe and effective vaccine adjuvant","volume":"65","author":"Casella","year":"2008","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1586\/14760584.2013.811178","article-title":"Clinical vaccine development for H5N1 influenza","volume":"12","author":"Clegg","year":"2013","journal-title":"Expert Rev. Vaccines"},{"key":"ref_136","doi-asserted-by":"crossref","unstructured":"Coler, R.N., Bertholet, S., Moutaftsi, M., Guderian, J.A., Windish, H.P., Baldwin, S.L., Laughlin, E.M., Duthie, M.S., Fox, C.B., and Carter, D. (2011). Development and characterization of synthetic glucopyranosyl lipid adjuvant system as a vaccine adjuvant. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0016333"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.jconrel.2017.09.021","article-title":"Intradermal vaccination with hollow microneedles: A comparative study of various protein antigen and adjuvant encapsulated nanoparticles","volume":"266","author":"Du","year":"2017","journal-title":"J. Control. Release"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1080\/21645515.2015.1010871","article-title":"Intradermal vaccination using the novel microneedle device MicronJet600: Past, present, and future","volume":"11","author":"Levin","year":"2015","journal-title":"Hum. Vaccines Immunother."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"383870","DOI":"10.4061\/2011\/383870","article-title":"Human Rabies in the WHO Southeast Asia Region: Forward Steps for Elimination","volume":"2011","author":"Gongal","year":"2011","journal-title":"Adv. PRev. Med."},{"key":"ref_140","doi-asserted-by":"crossref","unstructured":"Coler, R.N., Baldwin, S.L., Shaverdian, N., Bertholet, S., Reed, S.J., Raman, V.S., Lu, X., DeVos, J., Hancock, K., and Katz, J.M. (2010). A synthetic adjuvant to enhance and expand immune responses to influenza vaccines. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0013677"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1086\/590916","article-title":"Immune responses of healthy subjects to a single dose of intramuscular inactivated influenza A\/Vietnam\/1203\/2004 (H5N1) vaccine after priming with an antigenic variant","volume":"198","author":"Goji","year":"2008","journal-title":"J. Infect. Dis."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1038\/s41586-019-1453-3","article-title":"Cholera toxin promotes pathogen acquisition of host-derived nutrients","volume":"572","author":"Mekalanos","year":"2019","journal-title":"Nature"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1016\/S0264-410X(02)00532-7","article-title":"Maturation of human dendritic cells induced by the adjuvant cholera toxin: Role of cAMP on chemokine receptor expression","volume":"21","author":"Gagliardi","year":"2003","journal-title":"Vaccine"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"579","DOI":"10.3390\/vaccines3030579","article-title":"Cholera Toxin Subunit B as Adjuvant\u2014An Accelerator in Protective Immunity and a Break in Autoimmunity","volume":"3","author":"Stratmann","year":"2015","journal-title":"Vaccines"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"647","DOI":"10.4049\/jimmunol.153.2.647","article-title":"Production of IgE antibody and allergic sensitization of intestinal and peripheral tissues after oral immunization with protein Ag and cholera toxin","volume":"153","author":"Snider","year":"1994","journal-title":"J. Immunol."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"3892","DOI":"10.4049\/jimmunol.156.10.3892","article-title":"Acceleration of influenza virus clearance by Th1 cells in the nasal site of mice immunized intranasally with adjuvant-combined recombinant nucleoprotein","volume":"156","author":"Tamura","year":"1996","journal-title":"J. Immunol."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"10638","DOI":"10.1073\/pnas.1002348107","article-title":"Mucosal adjuvant activity of cholera toxin requires Th17 cells and protects against inhalation anthrax","volume":"107","author":"Datta","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1017\/S0950268809991014","article-title":"The epidemiology of primary amoebic meningoencephalitis in the USA, 1962\u20132008","volume":"138","author":"Yoder","year":"2009","journal-title":"Epidemiol. Infect."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1080\/14760584.2019.1604231","article-title":"Selection of adjuvants for vaccines targeting specific pathogens","volume":"18","author":"Sarkar","year":"2019","journal-title":"Expert Rev. Vaccines"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.juro.2007.08.122","article-title":"History of bacillus Calmette-Guerin and bladder cancer: An immunotherapy success story","volume":"179","author":"Herr","year":"2008","journal-title":"J. Urol."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"e16771","DOI":"10.1097\/MD.0000000000016771","article-title":"Immune adjuvant therapy using Bacillus Calmette-Guerin cell wall skeleton (BCG-CWS) in advanced malignancies: A phase 1 study of safety and immunogenicity assessments","volume":"98","author":"Nishida","year":"2019","journal-title":"Medicine"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"S78","DOI":"10.1016\/j.ijid.2021.03.060","article-title":"Bacille Calmette-Guerin (BCG) vaccine and potential cross-protection against SARS-CoV-2 infection-Assumptions, knowns, unknowns and need for developing an accurate scientific evidence base","volume":"113","author":"Nachega","year":"2021","journal-title":"Int. J. Infect. Dis."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"151600","DOI":"10.1016\/j.anndiagpath.2020.151600","article-title":"Strong homology between SARS-CoV-2 envelope protein and a Mycobacterium sp. antigen allows rapid diagnosis of Mycobacterial infections and may provide specific anti-SARS-CoV-2 immunity via the BCG vaccine","volume":"48","author":"Nuovo","year":"2020","journal-title":"Ann. Diagn. Pathol."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1093\/infdis\/jir769","article-title":"GLA-SE, a synthetic toll-like receptor 4 agonist, enhances T-cell responses to influenza vaccine in older adults","volume":"205","author":"Behzad","year":"2012","journal-title":"J. Infect. Dis."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1016\/j.immuni.2010.10.002","article-title":"Vaccine adjuvants: Putting innate immunity to work","volume":"33","author":"Coffman","year":"2010","journal-title":"Immunity"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/S0169-409X(98)00009-X","article-title":"Adjuvant activity of incomplete Freund\u2019s adjuvant","volume":"32","author":"Jensen","year":"1998","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.1002\/jps.21523","article-title":"Vaccine adjuvants: Current challenges and future approaches","volume":"98","author":"Torres","year":"2009","journal-title":"J. Pharm. Sci."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1093\/ilar.46.3.280","article-title":"Adjuvants and antibody production: Dispelling the myths associated with Freund\u2019s complete and other adjuvants","volume":"46","author":"Stills","year":"2005","journal-title":"ILAR J."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1080\/21645515.2015.1071455","article-title":"Safety and tolerability evaluation of the use of Montanide ISA\u212251 as vaccine adjuvant: A systematic review","volume":"12","author":"Liu","year":"2016","journal-title":"Hum. Vaccines Immunother."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1586\/14760584.1.1.111","article-title":"Montanide ISA 720 and 51: A new generation of water in oil emulsions as adjuvants for human vaccines","volume":"1","author":"Aucouturier","year":"2002","journal-title":"Expert Rev. Vaccines"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1586\/erv.12.140","article-title":"The history of MF59((R)) adjuvant: A phoenix that arose from the ashes","volume":"12","author":"Ott","year":"2013","journal-title":"Expert Rev. Vaccines"},{"key":"ref_162","first-page":"4341","article-title":"The mechanism of action of MF59\u2013An innately attractive adjuvant formulation","volume":"30","author":"Ott","year":"2011","journal-title":"Vaccine"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1186\/s12917-018-1719-2","article-title":"Development of a novel oil-in-water emulsion and evaluation of its potential adjuvant function in a swine influenza vaccine in mice","volume":"14","author":"Zhang","year":"2018","journal-title":"BMC Vet. Res."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1586\/14760584.2013.811188","article-title":"An update on safety and immunogenicity of vaccines containing emulsion-based adjuvants","volume":"12","author":"Fox","year":"2013","journal-title":"Expert Rev. Vaccines"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"3041","DOI":"10.1080\/21645515.2018.1495301","article-title":"Immunology and efficacy of MF59-adjuvanted vaccines","volume":"14","author":"Ko","year":"2018","journal-title":"Hum. Vaccin Immunother."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"152927","DOI":"10.1016\/j.phymed.2019.152927","article-title":"Vaccine adjuvant activity of emulsified oils from species of the Pinaceae family","volume":"64","author":"Fox","year":"2019","journal-title":"Phytomedicine"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"367202","DOI":"10.1155\/2015\/367202","article-title":"Methods for obtaining and determination of squalene from natural sources","volume":"2015","author":"Popa","year":"2015","journal-title":"BioMed. Res. Int."},{"key":"ref_168","doi-asserted-by":"crossref","unstructured":"Dubois Cauwelaert, N., Desbien, A.L., Hudson, T.E., Pine, S.O., Reed, S.G., Coler, R.N., and Orr, M.T. (2016). The TLR4 Agonist Vaccine Adjuvant, GLA-SE, Requires Canonical and Atypical Mechanisms of Action for TH1 Induction. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0146372"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.smim.2018.10.004","article-title":"Correlates of GLA family adjuvants\u2019 activities","volume":"39","author":"Reed","year":"2018","journal-title":"Semin. Immunol."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"4472","DOI":"10.1016\/j.vaccine.2015.07.025","article-title":"Enhanced immunogenicity of a respiratory syncytial virus (RSV) F subunit vaccine formulated with the adjuvant GLA-SE in cynomolgus macaques","volume":"33","author":"Patton","year":"2015","journal-title":"Vaccine"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1016\/j.vaccine.2016.11.092","article-title":"Immune protection conferred by recombinant MRLC (myosin regulatory light chain) antigen in TiterMax Gold(R) adjuvant against experimental fasciolosis in rats","volume":"35","author":"Henker","year":"2017","journal-title":"Vaccine"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1258\/002367798780599884","article-title":"Assessment of side effects induced by injection of different adjuvant\/antigen combinations in rabbits and mice","volume":"32","author":"Leenaars","year":"1998","journal-title":"Lab. Anim."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1093\/jnci\/52.1.95","article-title":"Biologically active components from mycobacterial cell walls. I. Isolation and composition of cell wall skeleton and component P3","volume":"52","author":"Azuma","year":"1974","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1093\/ilar.37.3.119","article-title":"Review of Selected Adjuvants Used in Antibody Production","volume":"37","author":"Jennings","year":"1995","journal-title":"ILAR J."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1128\/CMR.7.3.277","article-title":"Molecular adjuvants and immunomodulators: New approaches to immunization","volume":"7","author":"Johnson","year":"1994","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/0022-1759(92)90093-9","article-title":"Comparison of Freund\u2019s and Ribi adjuvants for inducing antibodies to the synthetic antigen (TG)-AL in rabbits","volume":"152","author":"Deeb","year":"1992","journal-title":"J. Immunol. Methods"},{"key":"ref_177","first-page":"193","article-title":"Comparison of immune response potentiation and in vivo inflammatory effects of Freund\u2019s and RIBI adjuvants in mice","volume":"42","author":"Lipman","year":"1992","journal-title":"Lab. Anim. Sci."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1007\/978-1-60761-585-9_19","article-title":"Adjuvant activity of cytokines","volume":"626","author":"Tovey","year":"2010","journal-title":"Methods Mol. Biol."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/S0169-409X(01)00170-3","article-title":"Cytokines as adjuvants for the induction of mucosal immunity","volume":"51","author":"Boyaka","year":"2001","journal-title":"Adv. Drug Deliv Rev."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1097\/AIA.0b013e318034194e","article-title":"Cytokines, inflammation, and pain","volume":"45","author":"Zhang","year":"2007","journal-title":"Int. Anesthesiol. Clin."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"12703","DOI":"10.1128\/JVI.01182-10","article-title":"Interleukin-1 family cytokines as mucosal vaccine adjuvants for induction of protective immunity against influenza virus","volume":"84","author":"Kayamuro","year":"2010","journal-title":"J. Virol."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1007\/978-1-0716-0872-2_5","article-title":"Molecular Adjuvants for DNA Vaccines: Application, Design, Preparation, and Formulation","volume":"2197","author":"Sabbaghi","year":"2021","journal-title":"Methods Mol. Biol."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"17","DOI":"10.21775\/cimb.022.017","article-title":"Molecular Adjuvants for DNA Vaccines","volume":"22","author":"Li","year":"2017","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"2837","DOI":"10.1080\/21645515.2017.1330236","article-title":"Advancements in DNA vaccine vectors, non-mechanical delivery methods, and molecular adjuvants to increase immunogenicity","volume":"13","author":"Suschak","year":"2017","journal-title":"Hum. Vaccin Immunother."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1016\/j.bbamcr.2012.10.008","article-title":"GM-CSF promotes inflammatory dendritic cell formation but does not contribute to disease progression in experimental autoimmune myocarditis","volume":"1833","author":"Blyszczuk","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"873","DOI":"10.3389\/fimmu.2017.00873","article-title":"The Role of Interferons in Inflammation and Inflammasome Activation","volume":"8","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1515\/BC.2008.051","article-title":"Adjuvant activity of type I interferons","volume":"389","author":"Tovey","year":"2008","journal-title":"Biol. Chem."},{"key":"ref_188","doi-asserted-by":"crossref","unstructured":"Zanetti, B.F., Ferreira, C.P., Vasconcelos, J.R.C., and Han, S.W. (2021). Adjuvant properties of IFN-gamma and GM-CSF in the scFv6.C4 DNA vaccine against CEA-expressing tumors. Gene Ther.","DOI":"10.1038\/s41434-021-00270-w"},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1038\/nri2691","article-title":"The IL-1 family: Regulators of immunity","volume":"10","author":"Sims","year":"2010","journal-title":"Nat. Rev. Immunol."},{"key":"ref_190","first-page":"779","article-title":"Novel adjuvants & delivery vehicles for vaccines development: A road ahead","volume":"138","author":"Mohan","year":"2013","journal-title":"Indian J. Med. Res."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.micinf.2011.10.006","article-title":"The role of interleukin-15 in inflammation and immune responses to infection: Implications for its therapeutic use","volume":"14","author":"Perera","year":"2012","journal-title":"Microbes Infect."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1093\/infdis\/jiw054","article-title":"Role of Granulocyte-Macrophage Colony-Stimulating Factor Signaling in Regulating Neutrophil Antifungal Activity and the Oxidative Burst During Respiratory Fungal Challenge","volume":"213","author":"Kasahara","year":"2016","journal-title":"J. Infect. Dis."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1111\/j.1348-0421.2006.tb03773.x","article-title":"Cytokine GM-CSF genetic adjuvant facilitates prophylactic DNA vaccine against pseudorabies virus through enhanced immune responses","volume":"50","author":"Yoon","year":"2006","journal-title":"Microbiol. Immunol."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.virol.2006.02.011","article-title":"Studies on GM-CSF DNA as an adjuvant for neutralizing Ab elicited by a DNA\/MVA immunodeficiency virus vaccine","volume":"352","author":"Robinson","year":"2006","journal-title":"Virology"},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1111\/j.1365-2036.2006.03035.x","article-title":"Meta-analysis: The adjuvant role of granulocyte macrophage-colony stimulating factor on immunological response to hepatitis B virus vaccine in end-stage renal disease","volume":"24","author":"Fabrizi","year":"2006","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"4860","DOI":"10.1046\/j.1432-1033.2002.03187.x","article-title":"Solution structure of the HIV gp120 C5 domain","volume":"269","author":"Guilhaudis","year":"2002","journal-title":"Eur. J. BioChem."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"2994","DOI":"10.1016\/j.vaccine.2004.12.006","article-title":"Type I IFN is a powerful mucosal adjuvant for a selective intranasal vaccination against influenza virus in mice and affects antigen capture at mucosal level","volume":"23","author":"Bracci","year":"2005","journal-title":"Vaccine"},{"key":"ref_198","doi-asserted-by":"crossref","unstructured":"Ye, L., Ohnemus, A., Ong, L.C., Gad, H.H., Hartmann, R., Lycke, N., and Staeheli, P. (2019). Type I and Type III Interferons Differ in Their Adjuvant Activities for Influenza Vaccines. J. Virol., 93.","DOI":"10.1128\/JVI.01262-19"},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"5344","DOI":"10.1016\/j.vaccine.2009.06.084","article-title":"Contrasting effects of type I interferon as a mucosal adjuvant for influenza vaccine in mice and humans","volume":"27","author":"Couch","year":"2009","journal-title":"Vaccine"},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/0264-410X(89)90162-X","article-title":"Effects of interferons on immune response to a synthetic peptide malaria sporozoite vaccine in non-immune adults","volume":"7","author":"Sturchler","year":"1989","journal-title":"Vaccine"},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1586\/erv.11.9","article-title":"IFN-alpha as a vaccine adjuvant: Recent insights into the mechanisms and perspectives for its clinical use","volume":"10","author":"Rizza","year":"2011","journal-title":"Expert Rev. Vaccines"},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1159\/000092487","article-title":"Co-expression of interleukin-2 by a bicistronic plasmid increases the efficacy of DNA immunization to prevent influenza virus infections","volume":"49","author":"Henke","year":"2006","journal-title":"Intervirology"},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"1685","DOI":"10.1007\/s10529-009-0061-y","article-title":"Enhancing immune responses against SARS-CoV nucleocapsid DNA vaccine by co-inoculating interleukin-2 expressing vector in mice","volume":"31","author":"Hu","year":"2009","journal-title":"Biotechnol. Lett."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"2377","DOI":"10.1111\/febs.14467","article-title":"A Guide to IL-1 family cytokines in adjuvanticity","volume":"285","author":"Lavelle","year":"2018","journal-title":"FEBS J."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1086\/314996","article-title":"Intranasal interleukin-12 is a powerful adjuvant for protective mucosal immunity","volume":"180","author":"Arulanandam","year":"1999","journal-title":"J. Infect. Dis."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"1925","DOI":"10.1128\/CVI.05117-11","article-title":"Intranasal administration of an inactivated Yersinia pestis vaccine with interleukin-12 generates protective immunity against pneumonic plague","volume":"18","author":"Kumar","year":"2011","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_207","doi-asserted-by":"crossref","unstructured":"Kalams, S.A., Parker, S., Jin, X., Elizaga, M., Metch, B., Wang, M., Hural, J., Lubeck, M., Eldridge, J., and Cardinali, M. (2012). Safety and immunogenicity of an HIV-1 gag DNA vaccine with or without IL-12 and\/or IL-15 plasmid cytokine adjuvant in healthy, HIV-1 uninfected adults. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0029231"},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"S370","DOI":"10.1086\/374751","article-title":"Interleukin-18 and host defense against infection","volume":"187","author":"Dinarello","year":"2003","journal-title":"J. Infect. Dis."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1099\/jmm.0.04998-0","article-title":"Enhancement of DNA vaccine potency against herpes simplex virus 1 by co-administration of an interleukin-18 expression plasmid as a genetic adjuvant","volume":"52","author":"Zhu","year":"2003","journal-title":"J. Med. Microbiol."},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"1980","DOI":"10.1016\/S0264-410X(02)00779-X","article-title":"Enhanced mucosal and systemic immune responses to a vaginal vaccine coadministered with RANTES-expressing plasmid DNA using in situ-gelling mucoadhesive delivery system","volume":"21","author":"Oh","year":"2003","journal-title":"Vaccine"},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/S1529-1049(02)00051-X","article-title":"The use of cytokines and chemokines as genetic adjuvants for plasmid DNA vaccines","volume":"2","author":"AEgan","year":"2002","journal-title":"Clinical. Appl. Immunol. Rev."},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1128\/JVI.75.2.569-578.2001","article-title":"Modulation of immunity against herpes simplex virus infection via mucosal genetic transfer of plasmid DNA encoding chemokines","volume":"75","author":"Eo","year":"2001","journal-title":"J. Virol."},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1046\/j.1365-2567.1997.00117.x","article-title":"HIV-1-specific cell-mediated immunity is enhanced by co-inoculation of TCA3 expression plasmid with DNA vaccine","volume":"90","author":"Tsuji","year":"1997","journal-title":"Immunology"},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1517\/14656566.4.7.1105","article-title":"The imidazoquinolines and their place in the therapy of cutaneous disease","volume":"4","author":"Smith","year":"2003","journal-title":"Expert Opin Pharmacother."},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"46426","DOI":"10.1038\/srep46426","article-title":"A Formulated TLR7\/8 Agonist is a Flexible, Highly Potent and Effective Adjuvant for Pandemic Influenza Vaccines","volume":"7","author":"Fox","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_216","first-page":"503","article-title":"Nanoparticles and microparticles for drug and vaccine delivery","volume":"189","author":"Kreuter","year":"1996","journal-title":"J. Anat."},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1186\/s12951-021-00806-7","article-title":"Virus-like particles: Preparation, immunogenicity and their roles as nanovaccines and drug nanocarriers","volume":"19","author":"Nooraei","year":"2021","journal-title":"J. Nanobiotechnol."},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.clim.2017.08.004","article-title":"Adjuvant formulations for virus-like particle (VLP) based vaccines","volume":"183","author":"Cimica","year":"2017","journal-title":"Clin. Immunol."},{"key":"ref_219","doi-asserted-by":"crossref","unstructured":"Qian, C., Liu, X., Xu, Q., Wang, Z., Chen, J., Li, T., Zheng, Q., Yu, H., Gu, Y., and Li, S. (2020). Recent Progress on the Versatility of Virus-Like Particles. Vaccines, 8.","DOI":"10.3390\/vaccines8010139"},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"345","DOI":"10.3389\/fimmu.2018.00345","article-title":"Virus-Like Particle, Liposome, and Polymeric Particle-Based Vaccines against HIV-1","volume":"9","author":"Gao","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1016\/j.copbio.2004.10.005","article-title":"Liposomes and virosomes as delivery systems for antigens, nucleic acids and drugs","volume":"15","author":"Felnerova","year":"2004","journal-title":"Curr. Opin. Biotechnol."},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1515\/acph-2015-0019","article-title":"Virosome, a hybrid vehicle for efficient and safe drug delivery and its emerging application in cancer treatment","volume":"65","author":"Liu","year":"2015","journal-title":"Acta Pharm."},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"2046","DOI":"10.1016\/S0140-6736(14)61185-5","article-title":"Safety and tolerability of chikungunya virus-like particle vaccine in healthy adults: A phase 1 dose-escalation trial","volume":"384","author":"Chang","year":"2014","journal-title":"Lancet"},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1080\/14760584.2017.1383158","article-title":"9-Valent human papillomavirus vaccine: A review of the clinical development program","volume":"16","author":"Luxembourg","year":"2017","journal-title":"Expert Rev. Vaccines"},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"1951","DOI":"10.2147\/IDR.S178381","article-title":"Recombinant human papillomavirus nonavalent vaccine in the prevention of cancers caused by human papillomavirus","volume":"12","author":"Toh","year":"2019","journal-title":"Infect. Drug Resist."},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1111\/all.15091","article-title":"Development and preclinical evaluation of virus-like particle vaccine against COVID-19 infection","volume":"77","author":"Yilmaz","year":"2022","journal-title":"Allergy"},{"key":"ref_227","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1586\/erv.10.174","article-title":"CpG DNA as a vaccine adjuvant","volume":"10","author":"Bode","year":"2011","journal-title":"Expert Rev. Vaccines"},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.smim.2018.05.001","article-title":"Correlates of adjuvanticity: A review on adjuvants in licensed vaccines","volume":"39","author":"Rappuoli","year":"2018","journal-title":"Semin Immunol."},{"key":"ref_229","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1093\/intimm\/dxh025","article-title":"Polyriboinosinic polyribocytidylic acid [poly(I:C)]\/TLR3 signaling allows class I processing of exogenous protein and induction of HIV-specific CD8+ cytotoxic T lymphocytes","volume":"16","author":"Fujimoto","year":"2004","journal-title":"Int. Immunol."},{"key":"ref_230","doi-asserted-by":"crossref","first-page":"2910","DOI":"10.1128\/JVI.79.5.2910-2919.2005","article-title":"Synthetic double-stranded RNA poly(I:C) combined with mucosal vaccine protects against influenza virus infection","volume":"79","author":"Ichinohe","year":"2005","journal-title":"J. Virol."},{"key":"ref_231","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1186\/s13046-021-02017-2","article-title":"A systematic review on poly(I:C) and poly-ICLC in glioblastoma: Adjuvants coordinating the unlocking of immunotherapy","volume":"40","author":"Verhezen","year":"2021","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_232","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1128\/CVI.00065-14","article-title":"Safety and immunogenicity of a vero cell culture-derived whole-virus H5N1 influenza vaccine in chronically ill and immunocompromised patients","volume":"21","author":"Geisberger","year":"2014","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_233","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1097\/MPG.0b013e318156050d","article-title":"Neonatal sublingual vaccination with Salmonella proteins and adjuvant cholera toxin or CpG oligodeoxynucleotides induces mucosal and systemic immunity in mice","volume":"46","author":"Huang","year":"2008","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_234","doi-asserted-by":"crossref","first-page":"1478","DOI":"10.1016\/j.micinf.2007.08.002","article-title":"Systemic but not mucosal immunity induced by AVA prevents inhalational anthrax","volume":"9","author":"Klinman","year":"2007","journal-title":"Microbes Infect."},{"key":"ref_235","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1016\/j.vaccine.2017.12.038","article-title":"Immunogenicity of a two-dose investigational hepatitis B vaccine, HBsAg-1018, using a toll-like receptor 9 agonist adjuvant compared with a licensed hepatitis B vaccine in adults","volume":"36","author":"Jackson","year":"2018","journal-title":"Vaccine"},{"key":"ref_236","doi-asserted-by":"crossref","first-page":"20085","DOI":"10.1038\/s41598-020-77077-z","article-title":"Development of CpG-adjuvanted stable prefusion SARS-CoV-2 spike antigen as a subunit vaccine against COVID-19","volume":"10","author":"Kuo","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_237","doi-asserted-by":"crossref","first-page":"3051","DOI":"10.1016\/j.vaccine.2013.04.063","article-title":"Randomized, double-blind, placebo-controlled, safety and immunogenicity study of 4 formulations of Anthrax Vaccine Adsorbed plus CPG 7909 (AV7909) in healthy adult volunteers","volume":"31","author":"Hopkins","year":"2013","journal-title":"Vaccine"},{"key":"ref_238","doi-asserted-by":"crossref","first-page":"3136","DOI":"10.1016\/j.vaccine.2004.01.058","article-title":"Safety and immunogenicity of CPG 7909 injection as an adjuvant to Fluarix influenza vaccine","volume":"22","author":"Cooper","year":"2004","journal-title":"Vaccine"},{"key":"ref_239","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1111\/j.1365-3083.2008.02225.x","article-title":"IC31, a two-component novel adjuvant mixed with a conjugate vaccine enhances protective immunity against pneumococcal disease in neonatal mice","volume":"69","author":"Olafsdottir","year":"2009","journal-title":"Scand. J. Immunol."},{"key":"ref_240","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1186\/1556-276X-8-102","article-title":"Liposome: Classification, preparation, and applications","volume":"8","author":"Akbarzadeh","year":"2013","journal-title":"Nanoscale Res. Lett"},{"key":"ref_241","doi-asserted-by":"crossref","first-page":"1877","DOI":"10.2217\/nnm.12.157","article-title":"Liposome-based delivery system for vaccine candidates: Constructing an effective formulation","volume":"7","author":"Giddam","year":"2012","journal-title":"Nanomedicine"},{"key":"ref_242","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1177\/2051013614541440","article-title":"Liposomes as vaccine delivery systems: A review of the recent advances","volume":"2","author":"Schwendener","year":"2014","journal-title":"Ther. Adv. Vaccines"},{"key":"ref_243","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1007\/s11095-006-9180-5","article-title":"Lipid-based nanoparticles for nucleic acid delivery","volume":"24","author":"Li","year":"2007","journal-title":"Pharm. Res."},{"key":"ref_244","doi-asserted-by":"crossref","unstructured":"Zhang, C., Ma, Y., Zhang, J., Kuo, J.C., Zhang, Z., Xie, H., Zhu, J., and Liu, T. (2022). Modification of Lipid-Based Nanoparticles: An Efficient Delivery System for Nucleic Acid-Based Immunotherapy. Molecules, 27.","DOI":"10.3390\/molecules27061943"},{"key":"ref_245","doi-asserted-by":"crossref","unstructured":"Agger, E.M., Rosenkrands, I., Hansen, J., Brahimi, K., Vandahl, B.S., Aagaard, C., Werninghaus, K., Kirschning, C., Lang, R., and Christensen, D. (2008). Cationic liposomes formulated with synthetic mycobacterial cordfactor (CAF01): A versatile adjuvant for vaccines with different immunological requirements. PLoS ONE, 3.","DOI":"10.1371\/journal.pone.0003116"},{"key":"ref_246","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.smim.2018.10.003","article-title":"Immunocorrelates of CAF family adjuvants","volume":"39","author":"Pedersen","year":"2018","journal-title":"Semin. Immunol."},{"key":"ref_247","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.ijpharm.2009.10.043","article-title":"CAF01 liposomes as a mucosal vaccine adjuvant: In vitro and in vivo investigations","volume":"390","author":"Christensen","year":"2010","journal-title":"Int. J. Pharm."},{"key":"ref_248","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1038\/s41578-021-00358-0","article-title":"Lipid nanoparticles for mRNA delivery","volume":"6","author":"Hou","year":"2021","journal-title":"Nat. Rev. Mater."},{"key":"ref_249","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.actbio.2016.04.012","article-title":"Liposome-based intranasal delivery of lipopeptide vaccine candidates against group A streptococcus","volume":"41","author":"Ghaffar","year":"2016","journal-title":"Acta Biomater."},{"key":"ref_250","doi-asserted-by":"crossref","first-page":"127920","DOI":"10.1016\/j.bmcl.2021.127920","article-title":"Polyethylenimine quantity and molecular weight influence its adjuvanting properties in liposomal peptide vaccines","volume":"40","author":"Dai","year":"2021","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_251","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1038\/s41565-018-0271-3","article-title":"A malaria vaccine adjuvant based on recombinant antigen binding to liposomes","volume":"13","author":"Huang","year":"2018","journal-title":"Nat. Nanotechnol."},{"key":"ref_252","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1038\/s41541-021-00399-0","article-title":"Development of COVID-19 vaccine using a dual Toll-like receptor ligand liposome adjuvant","volume":"6","author":"Abhyankar","year":"2021","journal-title":"NPJ Vaccines"},{"key":"ref_253","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1056\/NEJMoa2035389","article-title":"Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine","volume":"384","author":"Baden","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_254","doi-asserted-by":"crossref","first-page":"2565","DOI":"10.1016\/j.vaccine.2010.01.029","article-title":"Phase 1 clinical trials of the safety and immunogenicity of adjuvanted plasmid DNA vaccines encoding influenza A virus H5 hemagglutinin","volume":"28","author":"Smith","year":"2010","journal-title":"Vaccine"},{"key":"ref_255","doi-asserted-by":"crossref","first-page":"963513","DOI":"10.1155\/2011\/963513","article-title":"Chlamydia trachomatis vaccine research through the years","volume":"2011","author":"Schautteet","year":"2011","journal-title":"Infect. Dis. Obstet Gynecol."},{"key":"ref_256","doi-asserted-by":"crossref","first-page":"1364","DOI":"10.1038\/s41390-020-01112-y","article-title":"The sixth revolution in pediatric vaccinology: Immunoengineering and delivery systems","volume":"89","author":"Soni","year":"2021","journal-title":"Pediatr. Res."},{"key":"ref_257","doi-asserted-by":"crossref","first-page":"5226","DOI":"10.1016\/j.vaccine.2018.07.040","article-title":"Polysaccharides as vaccine adjuvants","volume":"36","author":"Sun","year":"2018","journal-title":"Vaccine"},{"key":"ref_258","doi-asserted-by":"crossref","first-page":"88","DOI":"10.5582\/ddt.2015.01025","article-title":"Polysaccharides: Candidates of promising vaccine adjuvants","volume":"9","author":"Li","year":"2015","journal-title":"Drug Discov. Ther."},{"key":"ref_259","doi-asserted-by":"crossref","first-page":"1188","DOI":"10.1016\/S0264-410X(00)00309-1","article-title":"A mucosal vaccine against diphtheria: Formulation of cross reacting material (CRM(197)) of diphtheria toxin with chitosan enhances local and systemic antibody and Th2 responses following nasal delivery","volume":"19","author":"McNeela","year":"2000","journal-title":"Vaccine"},{"key":"ref_260","doi-asserted-by":"crossref","unstructured":"Mann, A.J., Noulin, N., Catchpole, A., Stittelaar, K.J., de Waal, L., Veldhuis Kroeze, E.J., Hinchcliffe, M., Smith, A., Montomoli, E., and Piccirella, S. (2014). Intranasal H5N1 vaccines, adjuvanted with chitosan derivatives, protect ferrets against highly pathogenic influenza intranasal and intratracheal challenge. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0093761"},{"key":"ref_261","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1211\/jpp.60.9.0001","article-title":"Potential prospects of chitosan derivative trimethyl chitosan chloride (TMC) as a polymeric absorption enhancer: Synthesis, characterization and applications","volume":"60","author":"Sahni","year":"2008","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_262","doi-asserted-by":"crossref","unstructured":"Zielinska, A., Carreiro, F., Oliveira, A.M., Neves, A., Pires, B., Venkatesh, D.N., Durazzo, A., Lucarini, M., Eder, P., and Silva, A.M. (2020). Polymeric Nanoparticles: Production, Characterization, Toxicology and Ecotoxicology. Molecules, 25.","DOI":"10.3390\/molecules25163731"},{"key":"ref_263","doi-asserted-by":"crossref","first-page":"2703","DOI":"10.2217\/nnm.14.156","article-title":"Poly(lactic acid) and poly(lactic-co-glycolic acid) particles as versatile carrier platforms for vaccine delivery","volume":"9","author":"Pavot","year":"2014","journal-title":"Nanomedicine"},{"key":"ref_264","doi-asserted-by":"crossref","first-page":"118731","DOI":"10.1016\/j.ijpharm.2019.118731","article-title":"Adjuvants and delivery systems based on polymeric nanoparticles for mucosal vaccines","volume":"572","author":"Jin","year":"2019","journal-title":"Int. J. Pharm."},{"key":"ref_265","doi-asserted-by":"crossref","first-page":"1","DOI":"10.35248\/2593-8509.17.2.113","article-title":"Poly (Lactic-Co-Glycolic) Acid (PLGA) Adjuvant for Immunotherapy","volume":"2","author":"Roopngam","year":"2017","journal-title":"Immunol. Disord. Immunother."},{"key":"ref_266","doi-asserted-by":"crossref","first-page":"1911","DOI":"10.2174\/092986707781368513","article-title":"Nanochemistry-based immunotherapy for HIV-1","volume":"14","author":"Lori","year":"2007","journal-title":"Curr. Med. Chem."},{"key":"ref_267","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1586\/erv.11.118","article-title":"DermaVir: A plasmid DNA-based nanomedicine therapeutic vaccine for the treatment of HIV\/AIDS","volume":"10","author":"Lori","year":"2011","journal-title":"Expert Rev. Vaccines"},{"key":"ref_268","doi-asserted-by":"crossref","first-page":"18803","DOI":"10.1038\/s41598-019-55088-9","article-title":"Induction of specific adaptive immune responses by immunization with newly designed artificial glycosphingolipids","volume":"9","author":"Okuda","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_269","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1007\/s11515-012-1194-2","article-title":"Boosting the Immune Response: The Use of iNKT cell ligands as vaccine adjuvants","volume":"7","author":"Subrahmanyam","year":"2012","journal-title":"Front. Biol."},{"key":"ref_270","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1007\/s00441-010-1023-3","article-title":"Invariant natural killer T cells: Bridging innate and adaptive immunity","volume":"343","author":"Parekh","year":"2011","journal-title":"Cell. Tissue Res."},{"key":"ref_271","doi-asserted-by":"crossref","first-page":"11252","DOI":"10.1073\/pnas.0604812103","article-title":"Glycolipid alpha-C-galactosylceramide is a distinct inducer of dendritic cell function during innate and adaptive immune responses of mice","volume":"103","author":"Fujii","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_272","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1007\/s00705-017-3230-7","article-title":"Adjuvant use of the NKT cell agonist alpha-galactosylceramide leads to enhancement of M2-based DNA vaccine immunogenicity and protective immunity against influenza A virus","volume":"162","author":"Fotouhi","year":"2017","journal-title":"Arch. Virol."},{"key":"ref_273","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1631\/jzus.2007.B0153","article-title":"Adjuvant effects of saponins on animal immune responses","volume":"8","author":"Rajput","year":"2007","journal-title":"J. Zhejiang Univ. Sci. B"},{"key":"ref_274","first-page":"e113","article-title":"QS-21: A Potent Vaccine Adjuvant","volume":"3","author":"Zhu","year":"2016","journal-title":"Nat. Prod. Chem. Res."},{"key":"ref_275","doi-asserted-by":"crossref","first-page":"439","DOI":"10.3109\/10409238.2014.953628","article-title":"Metabolic and functional diversity of saponins, biosynthetic intermediates and semi-synthetic derivatives","volume":"49","author":"Moses","year":"2014","journal-title":"Crit Rev. BioChem. Mol. Biol."},{"key":"ref_276","doi-asserted-by":"crossref","first-page":"152905","DOI":"10.1016\/j.phymed.2019.152905","article-title":"Updated insights into the mechanism of action and clinical profile of the immunoadjuvant QS-21: A review","volume":"60","year":"2019","journal-title":"Phytomedicine"},{"key":"ref_277","doi-asserted-by":"crossref","first-page":"2733","DOI":"10.1016\/S0264-410X(98)00499-X","article-title":"Influence of antigenic forms and adjuvants on the IgG subclass antibody response to Aujeszky\u2019s disease virus in mice","volume":"17","author":"Katayama","year":"1999","journal-title":"Vaccine"},{"key":"ref_278","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1007\/s12026-018-8991-x","article-title":"Matrix-M adjuvant enhances immunogenicity of both protein- and modified vaccinia virus Ankara-based influenza vaccines in mice","volume":"66","author":"Magnusson","year":"2018","journal-title":"Immunol. Res."},{"key":"ref_279","doi-asserted-by":"crossref","unstructured":"Wang, P. (2021). Natural and Synthetic Saponins as Vaccine Adjuvants. Vaccines, 9.","DOI":"10.3390\/vaccines9030222"},{"key":"ref_280","doi-asserted-by":"crossref","first-page":"2372","DOI":"10.1016\/j.bpj.2012.03.071","article-title":"Structure of immune stimulating complex matrices and immune stimulating complexes in suspension determined by small-angle X-ray scattering","volume":"102","author":"Pedersen","year":"2012","journal-title":"Biophys. J."},{"key":"ref_281","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1016\/j.micron.2006.03.016","article-title":"On the preparation, microscopic investigation and application of ISCOMs","volume":"37","author":"Myschik","year":"2006","journal-title":"Micron"},{"key":"ref_282","doi-asserted-by":"crossref","first-page":"1741","DOI":"10.1021\/acs.accounts.6b00242","article-title":"Development of Improved Vaccine Adjuvants Based on the Saponin Natural Product QS-21 through Chemical Synthesis","volume":"49","author":"Tan","year":"2016","journal-title":"Acc. Chem. Res."},{"key":"ref_283","doi-asserted-by":"crossref","first-page":"221","DOI":"10.14202\/vetworld.2018.221-226","article-title":"Intranasal administration of inactivated avian influenza virus of H5N1 subtype vaccine-induced systemic immune response in chicken and mice","volume":"11","author":"Suartha","year":"2018","journal-title":"Vet. World"},{"key":"ref_284","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1099\/jmm.0.040857-0","article-title":"ISCOMATRIX: A novel adjuvant for use in prophylactic and therapeutic vaccines against infectious diseases","volume":"61","author":"Becher","year":"2012","journal-title":"J. Med. Microbiol."},{"key":"ref_285","doi-asserted-by":"crossref","first-page":"1717","DOI":"10.3389\/fpls.2018.01717","article-title":"Role of Papain-Like Cysteine Proteases in Plant Development","volume":"9","author":"Liu","year":"2018","journal-title":"Front. Plant Sci."},{"key":"ref_286","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1007\/s11882-007-0055-6","article-title":"Proteases as Th2 adjuvants","volume":"7","author":"Chapman","year":"2007","journal-title":"Curr. Allergy Asthma Rep."},{"key":"ref_287","doi-asserted-by":"crossref","first-page":"297","DOI":"10.3390\/vaccines2020297","article-title":"Vaccine Potentiation by Combination Adjuvants","volume":"2","author":"Levast","year":"2014","journal-title":"Vaccines"},{"key":"ref_288","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1080\/14760584.2016.1213632","article-title":"Adjuvant system AS01: Helping to overcome the challenges of modern vaccines","volume":"16","author":"Didierlaurent","year":"2017","journal-title":"Expert Rev. Vaccines"},{"key":"ref_289","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1586\/14760584.6.5.723","article-title":"GlaxoSmithKline Adjuvant Systems in vaccines: Concepts, achievements and perspectives","volume":"6","author":"Garcon","year":"2007","journal-title":"Expert Rev. Vaccines"},{"key":"ref_290","doi-asserted-by":"crossref","first-page":"6186","DOI":"10.4049\/jimmunol.0901474","article-title":"AS04, an aluminum salt- and TLR4 agonist-based adjuvant system, induces a transient localized innate immune response leading to enhanced adaptive immunity","volume":"183","author":"Didierlaurent","year":"2009","journal-title":"J. Immunol."},{"key":"ref_291","doi-asserted-by":"crossref","unstructured":"Nadeem, A.Y., Shehzad, A., Islam, S.U., Al-Suhaimi, E.A., and Lee, Y.S. (2022). Mosquirix RTS, S\/AS01 Vaccine Development, Immunogenicity, and Efficacy. Vaccines, 10.","DOI":"10.3390\/vaccines10050713"},{"key":"ref_292","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1080\/21645515.2016.1225635","article-title":"From discovery to licensure, the Adjuvant System story","volume":"13","author":"Garcon","year":"2017","journal-title":"Hum. Vaccin Immunother."},{"key":"ref_293","doi-asserted-by":"crossref","unstructured":"Polhemus, M.E., Remich, S.A., Ogutu, B.R., Waitumbi, J.N., Otieno, L., Apollo, S., Cummings, J.F., Kester, K.E., Ockenhouse, C.F., and Stewart, A. (2009). Evaluation of RTS,S\/AS02A and RTS,S\/AS01B in adults in a high malaria transmission area. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0006465"},{"key":"ref_294","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1080\/21645515.2015.1065363","article-title":"Sustained immunogenicity of the HPV-16\/18 AS04-adjuvanted vaccine administered as a two-dose schedule in adolescent girls: Five-year clinical data and modeling predictions from a randomized study","volume":"12","author":"Romanowski","year":"2016","journal-title":"Hum. Vaccines Immunother."},{"key":"ref_295","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1111\/IGC.0b013e3181d373a5","article-title":"Efficacy of human papillomavirus 16\/18 AS04-adjuvanted vaccine in Japanese women aged 20 to 25 years: Interim analysis of a phase 2 double-blind, randomized, controlled trial","volume":"20","author":"Konno","year":"2010","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_296","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1097\/INF.0000000000002437","article-title":"Long-term Immunogenicity and Safety of the AS04-adjuvanted Human Papillomavirus-16\/18 Vaccine in Four- to Six-year-old Girls: Three-year Follow-up of a Randomized Phase III Trial","volume":"38","author":"Lin","year":"2019","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_297","doi-asserted-by":"crossref","first-page":"100353","DOI":"10.1016\/j.eclinm.2020.100353","article-title":"Immunogenicity and safety of the AS04-HPV-16\/18 and HPV-6\/11\/16\/18 human papillomavirus vaccines in asymptomatic young women living with HIV aged 15\u201325 years: A phase IV randomized comparative study","volume":"23","author":"Folschweiller","year":"2020","journal-title":"EClinicalMedicine"}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/10\/7\/1120\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:49:49Z","timestamp":1760140189000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/10\/7\/1120"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,13]]},"references-count":297,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2022,7]]}},"alternative-id":["vaccines10071120"],"URL":"https:\/\/doi.org\/10.3390\/vaccines10071120","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,13]]}}}