{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T02:56:47Z","timestamp":1791946607145,"version":"4.3.4"},"reference-count":268,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,8,11]],"date-time":"2022-08-11T00:00:00Z","timestamp":1660176000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CONICYT-CHILE FONDECYT","award":["1201600"],"award-info":[{"award-number":["1201600"]}]},{"name":"CONICYT-CHILE FONDECYT","award":["21200880"],"award-info":[{"award-number":["21200880"]}]},{"name":"CONICYT-CHILE FONDECYT","award":["21210946"],"award-info":[{"award-number":["21210946"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>New-generation vaccines, formulated with subunits or nucleic acids, are less immunogenic than classical vaccines formulated with live-attenuated or inactivated pathogens. This difference has led to an intensified search for additional potent vaccine adjuvants that meet safety and efficacy criteria and confer long-term protection. This review provides an overview of protein-based adjuvants (PBAs) obtained from different organisms, including bacteria, mollusks, plants, and humans. Notably, despite structural differences, all PBAs show significant immunostimulatory properties, eliciting B-cell- and T-cell-mediated immune responses to administered antigens, providing advantages over many currently adopted adjuvant approaches. Furthermore, PBAs are natural biocompatible and biodegradable substances that induce minimal reactogenicity and toxicity and interact with innate immune receptors, enhancing their endocytosis and modulating subsequent adaptive immune responses. We propose that PBAs can contribute to the development of vaccines against complex pathogens, including intracellular pathogens such as Mycobacterium tuberculosis, those with complex life cycles such as Plasmodium falciparum, those that induce host immune dysfunction such as HIV, those that target immunocompromised individuals such as fungi, those with a latent disease phase such as Herpes, those that are antigenically variable such as SARS-CoV-2 and those that undergo continuous evolution, to reduce the likelihood of outbreaks.<\/jats:p>","DOI":"10.3390\/pharmaceutics14081671","type":"journal-article","created":{"date-parts":[[2022,8,11]],"date-time":"2022-08-11T21:15:05Z","timestamp":1660252505000},"page":"1671","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":72,"title":["Protein-Based Adjuvants for Vaccines as Immunomodulators of the Innate and Adaptive Immune Response: Current Knowledge, Challenges, and Future Opportunities"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5677-920X","authenticated-orcid":false,"given":"Diego A.","family":"D\u00edaz-Dinamarca","sequence":"first","affiliation":[{"name":"Fundaci\u00f3n Ciencia y Tecnolog\u00eda para el Desarrollo (FUCITED), Santiago 7750000, Chile"},{"name":"Secci\u00f3n de Biotecnolog\u00eda, Departamento Agencia Nacional de Dispositivos M\u00e9dicos, Innovaci\u00f3n y Desarrollo, Instituto de Salud P\u00fablica de Chile, Santiago 7750000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle L.","family":"Salazar","sequence":"additional","affiliation":[{"name":"Fundaci\u00f3n Ciencia y Tecnolog\u00eda para el Desarrollo (FUCITED), Santiago 7750000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byron N.","family":"Castillo","sequence":"additional","affiliation":[{"name":"Fundaci\u00f3n Ciencia y Tecnolog\u00eda para el Desarrollo (FUCITED), Santiago 7750000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Augusto","family":"Manubens","sequence":"additional","affiliation":[{"name":"Fundaci\u00f3n Ciencia y Tecnolog\u00eda para el Desarrollo (FUCITED), Santiago 7750000, Chile"},{"name":"Biosonda Corporation, Santiago 7750000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7346-9043","authenticated-orcid":false,"given":"Abel E.","family":"Vasquez","sequence":"additional","affiliation":[{"name":"Secci\u00f3n de Biotecnolog\u00eda, Departamento Agencia Nacional de Dispositivos M\u00e9dicos, Innovaci\u00f3n y Desarrollo, Instituto de Salud P\u00fablica de Chile, Santiago 7750000, Chile"},{"name":"Facultad de Ciencias para el Cuidado de la Salud, Universidad San Sebasti\u00e1n, Providencia, Santiago 8320000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabi\u00e1n","family":"Salazar","sequence":"additional","affiliation":[{"name":"Fundaci\u00f3n Ciencia y Tecnolog\u00eda para el Desarrollo (FUCITED), Santiago 7750000, Chile"},{"name":"Medical Research Council Centre for Medical Mycology, University of Exeter, Exeter EX4 4QD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9711-2222","authenticated-orcid":false,"given":"Mar\u00eda In\u00e9s","family":"Becker","sequence":"additional","affiliation":[{"name":"Fundaci\u00f3n Ciencia y Tecnolog\u00eda para el Desarrollo (FUCITED), Santiago 7750000, Chile"},{"name":"Biosonda Corporation, Santiago 7750000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/j.cell.2020.09.040","article-title":"Why and How Vaccines Work","volume":"183","author":"Iwasaki","year":"2020","journal-title":"Cell"},{"key":"ref_2","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_3","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_4","doi-asserted-by":"crossref","first-page":"1814","DOI":"10.1080\/21645515.2015.1043501","article-title":"Safety Assessment of Adjuvanted Vaccines: Methodological Considerations","volume":"11","author":"Yarzabal","year":"2015","journal-title":"Hum. Vaccines Immunother."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/82_2018_112","article-title":"Adjuvants","volume":"Volume 428","author":"Hangartner","year":"2018","journal-title":"Vaccination Strategies Against Highly Variable Pathogens"},{"key":"ref_6","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_7","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1586\/14760584.6.5.685","article-title":"Relationship between Physical and Chemical Properties of Aluminum-Containing Adjuvants and Immunopotentiation","volume":"6","author":"Hem","year":"2007","journal-title":"Expert Rev. Vaccines"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1517\/17425247.2016.1151871","article-title":"Liposomal Adjuvants for Human Vaccines","volume":"13","author":"Alving","year":"2016","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_9","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_10","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_11","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.3389\/fimmu.2019.01144","article-title":"Bacterial Protein Toll-Like-Receptor Agonists: A Novel Perspective on Vaccine Adjuvants","volume":"10","author":"Kumar","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1038\/s41577-020-0358-6","article-title":"COVID-19 Vaccines: Neutralizing Antibodies and the Alum Advantage","volume":"20","author":"Hotez","year":"2020","journal-title":"Nat. Rev. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2563","DOI":"10.1016\/j.bbamcr.2014.05.014","article-title":"Cytokines and Chemokines: At the Crossroads of Cell Signalling and Inflammatory Disease","volume":"1843","author":"Turner","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_14","unstructured":"Mir, M.A., AlBaradie, R.S., and Alharbi, A.R. (2013). Regulation of Immune System by Costimulatory Molecules, Nova Science Publishers, Inc."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Pfeifer, B.A., and Hill, A. (2021). Vaccine Delivery and Immune Response Basics. Vaccine Delivery Technology, Methods in Molecular Biology; Springer.","DOI":"10.1007\/978-1-0716-0795-4"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2936","DOI":"10.3389\/fimmu.2018.02936","article-title":"Trained Immunity-Based Vaccines: A New Paradigm for the Development of Broad-Spectrum Anti-Infectious Formulations","volume":"9","author":"Conejero","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Bauer, S., Hartmann, G., and Akira, S. (2008). Toll-like Receptors (TLRs) and Innate Immunity. Handbook of Experimental Pharmacology, Springer.","DOI":"10.1007\/978-3-540-72167-3"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1146\/annurev-immunol-032712-095910","article-title":"Pathways of Antigen Processing","volume":"31","author":"Blum","year":"2013","journal-title":"Annu. Rev. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1016\/j.immuni.2020.05.005","article-title":"Transcriptional Networks Driving Dendritic Cell Differentiation and Function","volume":"52","author":"Nutt","year":"2020","journal-title":"Immunity"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1016\/j.cell.2019.03.016","article-title":"B Cell Responses: Cell Interaction Dynamics and Decisions","volume":"177","author":"Cyster","year":"2019","journal-title":"Cell"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1016\/j.jaci.2009.12.980","article-title":"Overview of the immune response","volume":"125","author":"Chaplin","year":"2010","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1101\/SQB.1989.054.01.003","article-title":"Pillars Article: Approaching the Asymptote? Evolution and Revolution in Immunology","volume":"54","author":"Janeway","year":"1989","journal-title":"Cold Spring Harb. Symp. Quant. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1146\/annurev.iy.12.040194.005015","article-title":"Tolerance, Danger, and the Extended Family","volume":"12","author":"Matzinger","year":"1994","journal-title":"Annu. Rev. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1016\/j.cell.2006.02.015","article-title":"Pathogen Recognition and Innate Immunity","volume":"124","author":"Akira","year":"2006","journal-title":"Cell"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1016\/S1471-4906(03)00242-4","article-title":"Leucine-Rich Repeats and Pathogen Recognition in Toll-like Receptors","volume":"24","author":"Bell","year":"2003","journal-title":"Trends Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1038\/nri2079","article-title":"The Family of Five: TIR-Domain-Containing Adaptors in Toll-like Receptor Signalling","volume":"7","author":"Bowie","year":"2007","journal-title":"Nat. Rev. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.immuni.2006.08.009","article-title":"Type I Inteferon Gene Induction by the Interferon Regulatory Factor Family of Transcription Factors","volume":"25","author":"Honda","year":"2006","journal-title":"Immunity"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2578","DOI":"10.1038\/s41467-021-22590-6","article-title":"MyD88 TIR Domain Higher-Order Assembly Interactions Revealed by Microcrystal Electron Diffraction and Serial Femtosecond Crystallography","volume":"12","author":"Clabbers","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3341","DOI":"10.1016\/j.vaccine.2010.08.002","article-title":"TLR-Based Immune Adjuvants","volume":"29","author":"Steinhagen","year":"2011","journal-title":"Vaccine"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1021\/acs.jmedchem.0c01627","article-title":"TLR2 Agonistic Small Molecules: Detailed Structure\u2013Activity Relationship, Applications, and Future Prospects","volume":"64","author":"Kaur","year":"2021","journal-title":"J. Med. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1128\/jb.169.3.929-933.1987","article-title":"Role of Porins in Outer Membrane Permeability","volume":"169","author":"Hancock","year":"1987","journal-title":"J. Bacteriol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1006\/jsbi.1997.3946","article-title":"General and Specific Porins from Bacterial Outer Membranes","volume":"121","author":"Schirmer","year":"1998","journal-title":"J. Struct. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1111\/j.1574-6968.1996.tb08030.x","article-title":"Crucial Domains Are Conserved in Enterobacteriaceae Porins","volume":"136","author":"Simonet","year":"1996","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1128\/MMBR.67.4.593-656.2003","article-title":"Molecular Basis of Bacterial Outer Membrane Permeability Revisited","volume":"67","author":"Nikaido","year":"2003","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1126\/science.1094114","article-title":"The Structure of a Mycobacterial Outer-Membrane Channel","volume":"303","author":"Faller","year":"2004","journal-title":"Science"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1128\/CMR.9.1.55","article-title":"Taxonomy, Biology, and Periodontal Aspects of Fusobacterium nucleatum","volume":"9","author":"Bolstad","year":"1996","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1128\/CVI.00236-12","article-title":"The FomA Porin from Fusobacterium nucleatum Is a Toll-Like Receptor 2 Agonist with Immune Adjuvant Activity","volume":"19","author":"Toussi","year":"2012","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1739","DOI":"10.1016\/j.molimm.2010.03.001","article-title":"34kDa MOMP of Shigella flexneri Promotes TLR2 Mediated Macrophage Activation with the Engagement of NF-\u03baB and p38 MAP Kinase Signaling","volume":"47","author":"Pore","year":"2010","journal-title":"Mol. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1128\/IAI.01062-12","article-title":"Toll-Like Receptor 2-Dependent Activity of Native Major Outer Membrane Protein Proteosomes of Chlamydia trachomatis","volume":"81","author":"Massari","year":"2013","journal-title":"Infect. Immun."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"812774","DOI":"10.3389\/fimmu.2022.812774","article-title":"Toll-Like Receptor Signaling and Its Role in Cell-Mediated Immunity","volume":"13","author":"Duan","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3076","DOI":"10.1016\/j.molimm.2009.06.006","article-title":"Porin of Shigella dysenteriae Directly Promotes Toll-like Receptor 2-Mediated CD4+ T Cell Survival and Effector Function","volume":"46","author":"Biswas","year":"2009","journal-title":"Mol. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1016\/j.molimm.2006.04.007","article-title":"Porin of Shigella dysenteriae Activates Mouse Peritoneal Macrophage Through Toll-like Receptors 2 and 6 to Induce Polarized Type I Response","volume":"44","author":"Biswas","year":"2007","journal-title":"Mol. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1111\/j.1365-2567.2004.02002.x","article-title":"Porin of Shigella dysenteriae Enhances Toll-like Receptors 2 and 6 of Mouse Peritoneal B-2 Cells and Induces the Expression of Immunoglobulin M, Immunoglobulin G2a and Immunoglobulin A","volume":"114","author":"Ray","year":"2005","journal-title":"Immunology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1016\/j.imbio.2015.06.009","article-title":"Vibrio cholerae Porin OmpU Mediates M1-Polarization of Macrophages\/Monocytes via TLR1\/TLR2 Activation","volume":"220","author":"Khan","year":"2015","journal-title":"Immunobiology"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2373","DOI":"10.4049\/jimmunol.176.4.2373","article-title":"Meningococcal Porin PorB Binds to TLR2 and Requires TLR1 for Signaling","volume":"176","author":"Massari","year":"2006","journal-title":"J. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.3389\/fimmu.2020.01254","article-title":"Toll-Like Receptor Ligand Based Adjuvant, PorB, Increases Antigen Deposition on Germinal Center Follicular Dendritic Cells While Enhancing the Follicular Dendritic Cells Network","volume":"11","author":"Lisk","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_47","first-page":"230","article-title":"Salmonella Typhi Porins OmpC and OmpF Are Potent Adjuvants for T-Dependent and T-Independent Antigens","volume":"8","author":"Pacheco","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Chatterjee, S., Dwivedi, V.P., Singh, Y., Siddiqui, I., Sharma, P., Van Kaer, L., Chattopadhyay, D., and Das, G. (2011). Early Secreted Antigen ESAT-6 of Mycobacterium tuberculosis Promotes Protective T Helper 17 Cell Responses in a Toll-Like Receptor-2-Dependent Manner. PLoS Pathog., 7.","DOI":"10.1371\/journal.ppat.1002378"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1038\/cmi.2014.28","article-title":"TLR2 and TLR4 Signaling Pathways Are Required for Recombinant Brucella abortus BCSP31-Induced Cytokine Production, Functional Upregulation of Mouse Macrophages, and the Th1 Immune Response In Vivo and In Vitro","volume":"11","author":"Li","year":"2014","journal-title":"Cell. Mol. Immunol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e00651-17","DOI":"10.1128\/IAI.00651-17","article-title":"Expression of Toll-Like Receptor 2 by Dendritic Cells Is Essential for the DnaJ-\u0394A146Ply-Mediated Th1 Immune Response against Streptococcus pneumoniae","volume":"86","author":"Wang","year":"2018","journal-title":"Infect. Immun."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"23","DOI":"10.3389\/fcimb.2016.00023","article-title":"Streptococcus pneumoniae Endopeptidase O (PepO) Elicits a Strong Innate Immune Response in Mice via TLR2 and TLR4 Signaling Pathways","volume":"6","author":"Zhang","year":"2016","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1007\/s00018-002-8471-1","article-title":"Pore-Forming Toxins","volume":"59","author":"Gilbert","year":"2002","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1038\/mi.2014.93","article-title":"A Novel TLR2 Agonist from Bordetella pertussis is a Potent Adjuvant that Promotes Protective Immunity with an Acellular Pertussis Vaccine","volume":"8","author":"Dunne","year":"2015","journal-title":"Mucosal Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"673","DOI":"10.4049\/jimmunol.177.1.673","article-title":"Conserved Nontypeable Haemophilus influenzae-Derived TLR2-Binding Lipopeptides Synergize with IFN-\u03b2 to Increase Cytokine Production by Resident Murine and Human Alveolar Macrophages","volume":"177","author":"Punturieri","year":"2006","journal-title":"J. Immunol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1016\/j.cell.2007.09.008","article-title":"Crystal Structure of the TLR1-TLR2 Heterodimer Induced by Binding of a Tri-Acylated Lipopeptide","volume":"130","author":"Jin","year":"2007","journal-title":"Cell"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1038\/288499a0","article-title":"Amino Acid Sequence Homology between Cholera Toxin and Escherichia coli Heat-Labile Toxin","volume":"288","author":"Dallas","year":"1980","journal-title":"Nature"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1006\/jmbi.1993.1209","article-title":"Refined Structure of Escherichia coli Heat-Labile Enterotoxin, a Close Relative of Cholera Toxin","volume":"230","author":"Sixma","year":"1993","journal-title":"J. Mol. Biol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1006\/jmbi.1995.0456","article-title":"The Three-Dimensional Crystal Structure of Cholera Toxin","volume":"251","author":"Zhang","year":"1995","journal-title":"J. Mol. Biol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1083\/jcb.200207120","article-title":"Unfolded Cholera Toxin Is Transferred to the ER Membrane and Released from Protein Disulfide Isomerase upon Oxidation by Ero1","volume":"159","author":"Tsai","year":"2002","journal-title":"J. Cell Biol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1007\/s00018-008-7496-5","article-title":"Cholera Toxin Structure, Gene Regulation and Pathophysiological and Immunological Aspects","volume":"65","author":"Holmgren","year":"2008","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.1021\/jp506509c","article-title":"Biophysical Characteristics of Cholera Toxin and Escherichia coli Heat-Labile Enterotoxin Structure and Chemistry Lead to Differential Toxicity","volume":"119","author":"Craft","year":"2015","journal-title":"J. Phys. Chem. B"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1038\/s41577-021-00583-2","article-title":"Mucosal Vaccines\u2014Fortifying the Frontiers","volume":"22","author":"Lavelle","year":"2022","journal-title":"Nat. Rev. Immunol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1038\/mi.2007.7","article-title":"Cholera toxin, E. coli Heat-Labile Toxin, and Non-Toxic Derivatives Induce Dendritic Cell Migration into the Follicle-Associated Epithelium of Peyer\u2019s Patches","volume":"1","author":"Anosova","year":"2008","journal-title":"Mucosal Immunol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2534","DOI":"10.1016\/S0264-410X(00)00553-3","article-title":"Mucosal Vaccines: Non Toxic Derivatives of LT and CT as Mucosal Adjuvants","volume":"19","author":"Pizza","year":"2001","journal-title":"Vaccine"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1038\/nri3251","article-title":"Recent Progress in Mucosal Vaccine Development: Potential and Limitations","volume":"12","author":"Lycke","year":"2012","journal-title":"Nat. Rev. Immunol."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Moore, P., He, K., and Tsai, B. (2013). Establishment of an In Vitro Transport Assay That Reveals Mechanistic Differences in Cytosolic Events Controlling Cholera Toxin and T-Cell Receptor \u03b1 Retro-Translocation. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0075801"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.3389\/fimmu.2019.01249","article-title":"ERdj5 in Innate Immune Cells Is a Crucial Factor for the Mucosal Adjuvanticity of Cholera Toxin","volume":"10","author":"Kim","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_68","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_69","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1586\/14760584.6.5.821","article-title":"Cholera Toxin, LT-I, LT-IIa and LT-IIb: The Critical Role of Ganglioside Binding in Immunomodulation by Type I and Type II Heat-Labile Enterotoxins","volume":"6","author":"Connell","year":"2007","journal-title":"Expert Rev. Vaccines"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"4811","DOI":"10.4049\/jimmunol.178.8.4811","article-title":"The A Subunit of Type IIb Enterotoxin (LT-IIb) Suppresses the Proinflammatory Potential of the B Subunit and Its Ability to Recruit and Interact with TLR2","volume":"178","author":"Liang","year":"2007","journal-title":"J. Immunol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"4302","DOI":"10.1016\/j.vaccine.2009.05.027","article-title":"In Vivo and In Vitro Adjuvant Activities of the B Subunit of Type IIb Heat-Labile Enterotoxin (LT-IIb-B5) from Escherichia coli","volume":"27","author":"Liang","year":"2009","journal-title":"Vaccine"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"7532","DOI":"10.1074\/jbc.M611722200","article-title":"Ganglioside GD1a Is an Essential Coreceptor for Toll-like Receptor 2 Signaling in Response to the B Subunit of Type IIb Enterotoxin","volume":"282","author":"Liang","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_73","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_74","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1038\/nri.2017.9","article-title":"Dying Cells Actively Regulate Adaptive Immune Responses","volume":"17","author":"Yatim","year":"2017","journal-title":"Nat. Rev. Immunol."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Kim, E.H., Woodruff, M.C., Grigoryan, L., Maier, B., Lee, S.H., Mandal, P., Cortese, M., Natrajan, M.S., Ravindran, R., and Ma, H. (2020). Squalene Emulsion-Based Vaccine Adjuvants Stimulate CD8 T Cell, but Not Antibody Responses, Through a RIPK3-Dependent Pathway. eLife, 9.","DOI":"10.7554\/eLife.52687"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1038\/nm.2403","article-title":"DNA Released from Dying Host Cells Mediates Aluminum Adjuvant Activity","volume":"17","author":"Marichal","year":"2011","journal-title":"Nat. Med."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1038\/sj.embor.7400205","article-title":"HMGB1 is an Endogenous Immune Adjuvant Released by Necrotic Cells","volume":"5","author":"Capobianco","year":"2004","journal-title":"EMBO Rep."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"30393","DOI":"10.1074\/jbc.M111.266528","article-title":"Toll-like Receptor 4 (TLR4) Is Essential for Hsp70-like Protein 1 (HSP70L1) to Activate Dendritic Cells and Induce Th1 Response","volume":"286","author":"Fang","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Diaz-Dinamarca, D.A., Manzo, R.A., Soto, D.A., Avenda\u00f1o-Valenzuela, M.J., Bastias, D.N., Soto, P.I., Escobar, D.F., Vasquez-Saez, V., Carri\u00f3n, F., and Pizarro-Ortega, M.S. (2020). Surface Immunogenic Protein of Streptococcus Group B Is an Agonist of Toll-Like Receptors 2 and 4 and a Potential Immune Adjuvant. Vaccines, 8.","DOI":"10.3390\/vaccines8010029"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"5610","DOI":"10.1128\/IAI.68.10.5610-5618.2000","article-title":"Identification of Group B Streptococcal Sip Protein, Which Elicits Cross-Protective Immunity","volume":"68","author":"Brodeur","year":"2000","journal-title":"Infect. Immun."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"5162","DOI":"10.1128\/IAI.69.8.5162-5165.2001","article-title":"Localization of Surface Immunogenic Protein on Group B Streptococcus","volume":"69","author":"Rioux","year":"2001","journal-title":"Infect. Immun."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.molimm.2019.04.025","article-title":"Cellular Immune Response Induced by Surface Immunogenic Protein with AbISCO-100 Adjuvant Vaccination Decreases Group B Streptococcus Vaginal Colonization","volume":"111","author":"Soto","year":"2019","journal-title":"Mol. Immunol."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Diaz-Dinamarca, D.A., Hernandez, C., Escobar, D.F., Soto, D.A., Mu\u00f1oz, G.A., Badilla, J.F., Manzo, R.A., Carri\u00f3n, F., Kalergis, A.M., and Vasquez, A.E. (2020). Mucosal Vaccination with Lactococcus lactis\u2014Secreting Surface Immunological Protein Induces Humoral and Cellular Immune Protection against Group B Streptococcus in a Murine Model. Vaccines, 8.","DOI":"10.3390\/vaccines8020146"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1007\/s12033-018-0065-8","article-title":"The Optimisation of the Expression of Recombinant Surface Immunogenic Protein of Group B Streptococcus in Escherichia coli by Response Surface Methodology Improves Humoral Immunity","volume":"60","author":"Jerias","year":"2018","journal-title":"Mol. Biotechnol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.molimm.2018.08.028","article-title":"Oral Vaccine Based on a Surface Immunogenic Protein Mixed with Alum Promotes a Decrease in Streptococcus agalactiae Vaginal Colonization in a Mouse Model","volume":"103","author":"Soto","year":"2018","journal-title":"Mol. Immunol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1016\/j.imbio.2016.08.013","article-title":"Pneumococcal DnaJ Modulates Dendritic Cell-Mediated Th1 and Th17 Immune Responses Through Toll-like Receptor 4 Signaling Pathway","volume":"222","author":"Wu","year":"2017","journal-title":"Immunobiology"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1966","DOI":"10.1073\/pnas.0435928100","article-title":"Recognition of Pneumolysin by Toll-like Receptor 4 Confers Resistance to Pneumococcal Infection","volume":"100","author":"Malley","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"686","DOI":"10.3389\/fimmu.2017.00686","article-title":"Subcutaneous Immunization with Fusion Protein DnaJ-\u0394A146Ply without Additional Adjuvants Induces Both Humoral and Cellular Immunity against Pneumococcal Infection Partially Depending on TLR4","volume":"8","author":"Su","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"5200","DOI":"10.4049\/jimmunol.0902209","article-title":"The Protein Moiety of Brucella abortus Outer Membrane Protein 16 Is a New Bacterial Pathogen-Associated Molecular Pattern That Activates Dendritic Cells In Vivo, Induces a Th1 Immune Response, and Is a Promising Self-Adjuvanting Vaccine against Systemic and Oral Acquired Brucellosis","volume":"184","author":"Pasquevich","year":"2010","journal-title":"J. Immunol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2366","DOI":"10.4049\/jimmunol.176.4.2366","article-title":"A Polymeric Bacterial Protein Activates Dendritic Cells via TLR4","volume":"176","author":"Berguer","year":"2006","journal-title":"J. Immunol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1957","DOI":"10.1002\/eji.201445329","article-title":"Mycobacterium tuberculosis RpfE Promotes Simultaneous Th1- and Th17-Type T-Cell Immunity via TLR4-Dependent Maturation of Dendritic Cells: Cellular Immune Response","volume":"45","author":"Choi","year":"2015","journal-title":"Eur. J. Immunol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"2858","DOI":"10.1158\/0008-5472.CAN-10-3487","article-title":"Enhanced Efficacy of Therapeutic Cancer Vaccines Produced by Co-Treatment with Mycobacterium tuberculosis Heparin-Binding Hemagglutinin, a Novel TLR4 Agonist","volume":"71","author":"Jung","year":"2011","journal-title":"Cancer Res."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Lee, S.J., Shin, S.J., Lee, M.H., Lee, M.-G., Kang, T.H., Park, W.S., Soh, B.Y., Park, J.H., Shin, Y.K., and Kim, H.W. (2014). A Potential Protein Adjuvant Derived from Mycobacterium tuberculosis Rv0652 Enhances Dendritic Cells-Based Tumor Immunotherapy. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0104351"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"95","DOI":"10.3389\/fcimb.2018.00095","article-title":"Mycobacterium tuberculosis GrpE, A Heat-Shock Stress Responsive Chaperone, Promotes Th1-Biased T Cell Immune Response via TLR4-Mediated Activation of Dendritic Cells","volume":"8","author":"Kim","year":"2018","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"38609","DOI":"10.1074\/jbc.M112.391060","article-title":"Mycobacterium paratuberculosis CobT Activates Dendritic Cells via Engagement of Toll-like Receptor 4 Resulting in Th1 Cell Expansion","volume":"287","author":"Byun","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/s10020-018-0023-8","article-title":"Exploring the Biological Functional Mechanism of the HMGB1\/TLR4\/MD-2 Complex by Surface Plasmon Resonance","volume":"24","author":"He","year":"2018","journal-title":"Mol. Med."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.bbagrm.2009.11.019","article-title":"Targeting HMGB1 in inflammation","volume":"1799","author":"Yang","year":"2010","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"19546","DOI":"10.1074\/jbc.RA119.009525","article-title":"N-Glycosylation of Mollusk hemocyanins Contributes to Their Structural Stability and Immunomodulatory Properties in Mammals","volume":"294","author":"Salazar","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.3389\/fimmu.2019.01136","article-title":"TLR4, but Neither Dectin-1 nor Dectin-2, Participates in the Mollusk Hemocyanin-Induced Proinflammatory Effects in Antigen-Presenting Cells from Mammals","volume":"10","author":"Salazar","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Duc, G.H.T. (2014). Mollusk Hemocyanins as Natural Immunostimulants in Biomedical Applications. Immune Response Activation, InTech.","DOI":"10.5772\/57004"},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Arancibia, S., Espinoza, C., Salazar, F., del Campo, M., Tampe, R., Zhong, T.-Y., de Ioannes, P., Moltedo, B., Ferreira, J., and Lavelle, E. (2014). A Novel Immunomodulatory Hemocyanin from the Limpet Fissurella latimarginata Promotes Potent Anti-Tumor Activity in Melanoma. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0087240"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"26134","DOI":"10.1074\/jbc.M400903200","article-title":"Hemocyanin of the Molluscan Concholepas concholepas Exhibits an Unusual Heterodecameric Array of Subunits","volume":"279","author":"Moltedo","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1016\/j.intimp.2008.12.011","article-title":"Immunodominant Role of CCHA Subunit of Concholepas Hemocyanin is Associated with Unique Biochemical Properties","volume":"9","author":"Becker","year":"2009","journal-title":"Int. Immunopharmacol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1715","DOI":"10.1002\/eji.202149225","article-title":"C-type Lectin Receptors MR and DC-SIGN Are Involved in Recognition of Hemocyanins, Shaping Their Immunostimulatory Effects on Human Dendritic Cells","volume":"51","author":"Villar","year":"2021","journal-title":"Eur. J. Immunol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"3114","DOI":"10.1016\/j.vaccine.2005.01.072","article-title":"A Bivalent Conjugate Vaccine in the Treatment of Biochemically Relapsed Prostate Cancer: A Study of Glycosylated MUC-2-KLH and Globo H-KLH Conjugate Vaccines Given with the New Semi-Synthetic Saponin Immunological Adjuvant GPI-0100 OR QS-21","volume":"23","author":"Slovin","year":"2005","journal-title":"Vaccine"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1016\/j.bcp.2011.03.010","article-title":"Plant Lectins are Novel Toll-like Receptor Agonists","volume":"81","author":"Unitt","year":"2011","journal-title":"Biochem. Pharmacol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.2174\/1389201020666190716110705","article-title":"Plant Phenolics and Lectins as Vaccine Adjuvants","volume":"20","author":"Irais","year":"2019","journal-title":"Curr. Pharm. Biotechnol."},{"key":"ref_108","first-page":"1376140","article-title":"Mistletoe-Based Drugs Work in Synergy with Radio-Chemotherapy in the Treatment of Glioma In Vitro and In Vivo in Glioblastoma Bearing Mice","volume":"2019","author":"Miemietz","year":"2019","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1046\/j.1365-2567.2002.01492.x","article-title":"Mistletoe Lectins Enhance Immune Responses to Intranasally Co-Administered Herpes Simplex Virus Glycoprotein D2","volume":"107","author":"Lavelle","year":"2002","journal-title":"Immunology"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1080\/10611860410001693733","article-title":"Immunological Implications of the Use of Plant Lectins for Drug and Vaccine Targeting to the Gastrointestinal Tract","volume":"12","author":"Lavelle","year":"2004","journal-title":"J. Drug Target."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"20","DOI":"10.3389\/fvets.2019.00020","article-title":"Promising Plant-Derived Adjuvants in the Development of Coccidial Vaccines","volume":"6","author":"Sander","year":"2019","journal-title":"Front. Vet. Sci."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.cbpb.2010.04.012","article-title":"Structure of Hemocyanin from garden snail Helix lucorum","volume":"157","author":"Velkova","year":"2010","journal-title":"Comp. Biochem. Physiol. Part B Biochem. Mol. Biol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1042\/bj3150139","article-title":"Rapana thomasiana grosse (gastropoda) Haemocyanin: Spectroscopic Studies of the Structure in Solution and the Conformational Stability of the Native Protein and Its Structural Subunits","volume":"315","author":"Dolashka","year":"1996","journal-title":"Biochem. J."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1016\/S0968-4328(99)00145-6","article-title":"Haliotis tuberculata hemocyanin (HtH): Analysis of Oligomeric Stability of HtH1 and HtH2, and Comparison with Keyhole Limpet Hemocyanin KLH1 and KLH2","volume":"31","author":"Harris","year":"2000","journal-title":"Micron"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1016\/S0968-4328(99)00036-0","article-title":"Keyhole Limpet Hemocyanin (KLH): A Biomedical Review","volume":"30","author":"Harris","year":"1999","journal-title":"Micron"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1016\/j.jmb.2008.10.080","article-title":"Keyhole Limpet Hemocyanin: 9-\u00c5 CryoEM Structure and Molecular Model of the KLH1 Didecamer Reveal the Interfaces and Intricate Topology of the 160 Functional Units","volume":"385","author":"Gatsogiannis","year":"2009","journal-title":"J. Mol. Biol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1007\/978-3-030-41769-7_7","article-title":"Molluscan Hemocyanins","volume":"Volume 94","author":"Hoeger","year":"2020","journal-title":"Vertebrate and Invertebrate Respiratory Proteins, Lipoproteins and other Body Fluid Proteins"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1840","DOI":"10.1016\/j.bbapap.2013.02.020","article-title":"Evolution of Molluscan Hemocyanin Structures","volume":"1834","author":"Markl","year":"2013","journal-title":"Biochim. Biophys. Acta Proteins Proteom."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1007\/s12551-017-0349-4","article-title":"Molluscan Hemocyanin: Structure, Evolution, and Physiology","volume":"10","author":"Kato","year":"2018","journal-title":"Biophys. Rev."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"40731","DOI":"10.1074\/jbc.M505985200","article-title":"Identification and Characterization of Keyhole Limpet Hemocyanin N-Glycans Mediating Cross-Reactivity with Schistosoma mansoni","volume":"280","author":"Geyer","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.carres.2017.06.012","article-title":"N-Glycan Structures of \u03b2-HlH Subunit of Helix lucorum hemocyanin","volume":"449","author":"Velkova","year":"2017","journal-title":"Carbohydr. Res."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1016\/j.bbrc.2005.03.217","article-title":"Mass Spectral Evidence for N-Glycans with Branching on Fucose in a Molluscan Hemocyanin","volume":"331","author":"Gielens","year":"2005","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1016\/j.bbrc.2007.07.098","article-title":"Involvement of Glycan Chains in the Antigenicity of Rapana thomasiana Hemocyanin","volume":"361","author":"Siddiqui","year":"2007","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/S0165-2478(99)00079-6","article-title":"The Adjuvant Effect of Jacalin on the Mouse Humoral Immune Response to Trinitrophenyl and Trypanosoma cruzi","volume":"68","author":"Albuquerque","year":"1999","journal-title":"Immunol. Lett."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1016\/S1567-5769(01)00024-8","article-title":"Cellular and Humoral Adjuvant Activity of Lectins Isolated from Korean Mistletoe (Viscum album colaratum)","volume":"1","author":"Yoon","year":"2001","journal-title":"Int. Immunopharmacol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1820","DOI":"10.3389\/fimmu.2017.01820","article-title":"Targeting and Recognition of Toll-Like Receptors by Plant and Pathogen Lectins","volume":"8","author":"Gay","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"9183","DOI":"10.1016\/j.vaccine.2011.09.136","article-title":"ArtinM, a d-mannose-Binding Lectin from Artocarpus integrifolia, Plays a Potent Adjuvant and Immunostimulatory Role in Immunization against Neospora caninum","volume":"29","author":"Cardoso","year":"2011","journal-title":"Vaccine"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"9247","DOI":"10.1073\/pnas.0502040102","article-title":"Evasion of Toll-like receptor 5 by flagellated bacteria","volume":"102","author":"Smith","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1038\/35074106","article-title":"The Innate Immune Response to Bacterial Flagellin Is Mediated by Toll-like Receptor 5","volume":"410","author":"Hayashi","year":"2001","journal-title":"Nature"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1007\/s12551-017-0378-z","article-title":"Bacterial Flagellar Axial Structure and Its Construction","volume":"10","author":"Imada","year":"2018","journal-title":"Biophys. Rev."},{"key":"ref_131","first-page":"521","article-title":"Role of the Outermost Subdomain of Salmonella flagellin in the Filament Structure Revealed by Electron Cryomicroscopy","volume":"284","author":"Yamashita","year":"1997","journal-title":"J. Mol. Biol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1038\/35066504","article-title":"Structure of the Bacterial Flagellar Protofilament and Implications for a Switch for Supercoiling","volume":"410","author":"Samatey","year":"2001","journal-title":"Nature"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"5667","DOI":"10.1074\/jbc.M307759200","article-title":"Identification of Conserved Domains in Salmonella muenchen Flagellin That Are Essential for Its Ability to Activate TLR5 and to Induce an Inflammatory Response in Vitro","volume":"279","author":"Murthy","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"40456","DOI":"10.1074\/jbc.M206851200","article-title":"Two Nonadjacent Regions in Enteroaggregative Escherichia coli Flagellin Are Required for Activation of Toll-like Receptor 5","volume":"277","author":"Donnelly","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"7009","DOI":"10.4049\/jimmunol.167.12.7009","article-title":"Salmonella Flagellin-Dependent Proinflammatory Responses Are Localized to the Conserved Amino and Carboxyl Regions of the Protein","volume":"167","author":"Wong","year":"2001","journal-title":"J. Immunol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s13567-017-0497-3","article-title":"Recombinant Chicken Interleukin-7 as a Potent Adjuvant Increases the Immunogenicity and Protection of Inactivated Infectious Bursal Disease Vaccine","volume":"49","author":"Cui","year":"2018","journal-title":"Vet. Res."},{"key":"ref_137","doi-asserted-by":"crossref","unstructured":"Rady, H.F., Dai, G., Huang, W., Shellito, J.E., and Ramsay, A.J. (2016). Flagellin Encoded in Gene-Based Vector Vaccines Is a Route-Dependent Immune Adjuvant. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0148701"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1128\/IAI.66.3.1127-1134.1998","article-title":"Salmonella Flagellin Induces Tumor Necrosis Factor Alpha in a Human Promonocytic Cell Line","volume":"66","author":"Blomfield","year":"1998","journal-title":"Infect. Immun."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"3619","DOI":"10.1128\/IAI.67.7.3619-3624.1999","article-title":"Salmonella typhi Flagella Are Potent Inducers of Proinflammatory Cytokine Secretion by Human Monocytes","volume":"67","author":"Wyant","year":"1999","journal-title":"Infect. Immun."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"5525","DOI":"10.1128\/IAI.68.10.5525-5529.2000","article-title":"High-Affinity Interaction between Gram-Negative Flagellin and a Cell Surface Polypeptide Results in Human Monocyte Activation","volume":"68","author":"McDermott","year":"2000","journal-title":"Infect. Immun."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"171","DOI":"10.3389\/fimmu.2020.00171","article-title":"The TLR5 Agonist Flagellin Shapes Phenotypical and Functional Activation of Lung Mucosal Antigen Presenting Cells in Neonatal Mice","volume":"11","author":"Sharma","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1126\/science.1215584","article-title":"Structural Basis of TLR5-Flagellin Recognition and Signaling","volume":"335","author":"Yoon","year":"2012","journal-title":"Science"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"4360","DOI":"10.1128\/IAI.67.9.4360-4366.1999","article-title":"Intranasal Administration of Synthetic Recombinant Peptide-Based Vaccine Protects Mice from Infection by Schistosoma mansoni","volume":"67","author":"Schechtman","year":"1999","journal-title":"Infect. Immun."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1089\/vim.2009.0107","article-title":"A Recombinant Flagellin-Poxvirus Fusion Protein Vaccine Elicits Complement-Dependent Protection Against Respiratory Challenge with Vaccinia Virus in Mice","volume":"23","author":"Delaney","year":"2010","journal-title":"Viral Immunol."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"2818","DOI":"10.1016\/j.vaccine.2010.02.004","article-title":"Immunogenic Properties of a Recombinant Fusion Protein Containing the C-Terminal 19kDa of Plasmodium falciparum Merozoite Surface Protein-1 and the Innate Immunity Agonist FliC Flagellin of Salmonella Typhimurium","volume":"28","author":"Bargieri","year":"2010","journal-title":"Vaccine"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1016\/j.vaccine.2017.12.001","article-title":"Self-Assembling Protein Nanoparticles with Built-In Flagellin Domains Increases Protective Efficacy of a Plasmodium falciparum Based Vaccine","volume":"36","author":"Kaba","year":"2018","journal-title":"Vaccine"},{"key":"ref_147","doi-asserted-by":"crossref","unstructured":"Ajamian, L., Melnychuk, L., Jean-Pierre, P., and Zaharatos, G.J. (2018). DNA Vaccine-Encoded Flagellin Can Be Used as an Adjuvant Scaffold to Augment HIV-1 Gp41 Membrane Proximal External Region Immunogenicity. Viruses, 10.","DOI":"10.3390\/v10030100"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1007\/s10875-007-9138-3","article-title":"Inhibition of Airway Allergic Disease by Co-Administration of Flagellin with Allergen","volume":"28","author":"Lee","year":"2008","journal-title":"J. Clin. Immunol."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1111\/all.12839","article-title":"Intralymphatic Treatment of Flagellin-Ovalbumin Mixture Reduced Allergic Inflammation in Murine Model of Allergic Rhinitis","volume":"71","author":"Kim","year":"2016","journal-title":"Allergy"},{"key":"ref_150","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\u2013Flagellin Fusion Vaccine (VAX125) in Healthy Young Adults","volume":"28","author":"Treanor","year":"2010","journal-title":"Vaccine"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"5761","DOI":"10.1016\/j.vaccine.2012.06.086","article-title":"Development of VAX128, a Recombinant Hemagglutinin (HA) Influenza-Flagellin Fusion Vaccine with Improved Safety and Immune Response","volume":"30","author":"Taylor","year":"2012","journal-title":"Vaccine"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"151962","DOI":"10.1016\/j.imbio.2020.151962","article-title":"Identification of a Novel TLR5 Agonist Derived from the P97 Protein of Mycoplasma hyopneumoniae","volume":"225","author":"Gauthier","year":"2020","journal-title":"Immunobiology"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"18379","DOI":"10.1038\/srep18379","article-title":"Functional Properties of Flagellin as a Stimulator of Innate Immunity","volume":"6","author":"Lu","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1038\/s41419-021-03654-3","article-title":"Synergistic Effect of the TLR5 Agonist CBLB502 and Its Downstream Effector IL-22 against Liver Injury","volume":"12","author":"Melin","year":"2021","journal-title":"Cell Death Dis."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"4719","DOI":"10.4049\/jimmunol.1201206","article-title":"A TLR5 Agonist Enhances CD8+ T Cell-Mediated Graft-versus-Tumor Effect without Exacerbating Graft-versus-Host Disease","volume":"189","author":"Ding","year":"2012","journal-title":"J. Immunol."},{"key":"ref_156","unstructured":"Cummings, R.D., and McEver, R.P. (2009). C-Type Lectins. Essentials of Glycobiology, Cold Spring Harbor. [2nd ed.]."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1111\/cmi.12249","article-title":"Signaling C-Type Lectin Receptors, Microbial Recognition and Immunity","volume":"16","author":"Hoving","year":"2014","journal-title":"Cell. Microbiol."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"2118","DOI":"10.4049\/jimmunol.168.5.2118","article-title":"The Dendritic Cell-Specific Adhesion Receptor DC-SIGN Internalizes Antigen for Presentation to T Cells","volume":"168","author":"Engering","year":"2002","journal-title":"J. Immunol."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"7057","DOI":"10.4049\/jimmunol.1000164","article-title":"Partial Redundancy of the Pattern Recognition Receptors, Scavenger Receptors, and C-Type Lectins for the Long-Term Control of Mycobacterium tuberculosis Infection","volume":"184","author":"Court","year":"2010","journal-title":"J. Immunol."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1016\/j.imbio.2012.06.005","article-title":"Mincle Is Not Essential for Controlling Mycobacterium tuberculosis Infection","volume":"218","author":"Heitmann","year":"2013","journal-title":"Immunobiology"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.fsi.2010.09.018","article-title":"Marine Gastropod Hemocyanins as Adjuvants of Non-Conjugated Bacterial and Viral Proteins","volume":"30","author":"Gesheva","year":"2011","journal-title":"Fish Shellfish Immunol."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.intimp.2015.03.011","article-title":"Helix pomatia Hemocyanin\u2014A Novel Bio-Adjuvant for Viral and Bacterial Antigens","volume":"26","author":"Gesheva","year":"2015","journal-title":"Int. Immunopharmacol."},{"key":"ref_163","first-page":"7076942","article-title":"Immunotherapeutic Potential of Mollusk Hemocyanins in Combination with Human Vaccine Adjuvants in Murine Models of Oral Cancer","volume":"2019","author":"Villar","year":"2019","journal-title":"J. Immunol. Res."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"5165","DOI":"10.4049\/jimmunol.170.10.5165","article-title":"The Toll-Like Receptor 5 Stimulus Bacterial Flagellin Induces Maturation and Chemokine Production in Human Dendritic Cells","volume":"170","author":"Means","year":"2003","journal-title":"J. Immunol."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1038\/s41578-021-00372-2","article-title":"Designing Spatial and Temporal Control of Vaccine Responses","volume":"7","author":"Roth","year":"2021","journal-title":"Nat. Rev. Mater."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1038\/s41577-020-00479-7","article-title":"A Guide to Vaccinology: From Basic Principles to New Developments","volume":"21","author":"Pollard","year":"2021","journal-title":"Nat. Rev. Immunol."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.molimm.2018.12.024","article-title":"Inflammasome Activation and Th17 Responses","volume":"107","author":"Deng","year":"2019","journal-title":"Mol. Immunol."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1038\/sj.onc.1210910","article-title":"TLR Ligand Suppression or Enhancement of Treg Cells? A Double-Edged Sword in Immunity to Tumours","volume":"27","author":"Conroy","year":"2008","journal-title":"Oncogene"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"2889","DOI":"10.4049\/jimmunol.1002955","article-title":"Memory CD4 T Cells That Express CXCR5 Provide Accelerated Help to B Cells","volume":"186","author":"MacLeod","year":"2011","journal-title":"J. Immunol."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1016\/j.immuni.2019.04.011","article-title":"T Follicular Helper Cell Biology: A Decade of Discovery and Diseases","volume":"50","author":"Crotty","year":"2019","journal-title":"Immunity"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/j.immuni.2016.09.001","article-title":"Germinal Center B Cell Dynamics","volume":"45","author":"Mesin","year":"2016","journal-title":"Immunity"},{"key":"ref_172","first-page":"2680160","article-title":"Fundamentals and Methods for T- and B-Cell Epitope Prediction","volume":"2017","author":"Reche","year":"2017","journal-title":"J. Immunol. Res."},{"key":"ref_173","doi-asserted-by":"crossref","unstructured":"Nithichanon, A., Rinchai, D., Gori, A., Lassaux, P., Peri, C., Conchillio-Sol\u00e9, O., Ferrer-Navarro, M., Gourlay, L.J., Nardini, M., and Vila, J. (2015). Sequence- and Structure-Based Immunoreactive Epitope Discovery for Burkholderia pseudomallei Flagellin. PLoS Negl. Trop. Dis., 9.","DOI":"10.1371\/journal.pntd.0003917"},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"283","DOI":"10.3389\/fimmu.2020.00283","article-title":"Designs of Antigen Structure and Composition for Improved Protein-Based Vaccine Efficacy","volume":"11","author":"Saylor","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_175","unstructured":"(2022, June 14). Home\u2014ClinicalTrials.Gov, Available online: https:\/\/clinicaltrials.gov\/ct2\/home."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1126\/science.1154986","article-title":"An Agonist of Toll-Like Receptor 5 Has Radioprotective Activity in Mouse and Primate Models","volume":"320","author":"Burdelya","year":"2008","journal-title":"Science"},{"key":"ref_177","doi-asserted-by":"crossref","unstructured":"Hossain, M.S., Ramachandiran, S., Gewirtz, A.T., and Waller, E.K. (2014). Recombinant TLR5 Agonist CBLB502 Promotes NK Cell-Mediated Anti-CMV Immunity in Mice. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0096165"},{"key":"ref_178","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_179","doi-asserted-by":"crossref","first-page":"6759","DOI":"10.1016\/j.vaccine.2017.09.070","article-title":"A Phase I Safety and Immunogenicity Dose Escalation Trial of Plague Vaccine, Flagellin\/F1\/V, in Healthy Adult Volunteers (DMID 08-0066)","volume":"35","author":"Frey","year":"2017","journal-title":"Vaccine"},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"1773","DOI":"10.1517\/14712598.2015.1088519","article-title":"Update on Mucin-1 Immunotherapy in Cancer: A Clinical Perspective","volume":"15","author":"Rivalland","year":"2015","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_181","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_182","doi-asserted-by":"crossref","first-page":"105","DOI":"10.3390\/vaccines3010105","article-title":"M2e-Based Universal Influenza A Vaccines","volume":"3","author":"Deng","year":"2015","journal-title":"Vaccines"},{"key":"ref_183","doi-asserted-by":"crossref","unstructured":"Talbot, H.K., Rock, M.T., Johnson, C., Tussey, L., Kavita, U., Shanker, A., Shaw, A.R., and Taylor, D.N. (2010). Immunopotentiation of Trivalent Influenza Vaccine When Given with VAX102, a Recombinant Influenza M2e Vaccine Fused to the TLR5 Ligand Flagellin. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0014442"},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"5145","DOI":"10.1016\/j.vaccine.2011.05.041","article-title":"Safety and Immunogenicity of a Recombinant M2e\u2013Flagellin Influenza Vaccine (STF2.4xM2e) in Healthy Adults","volume":"29","author":"Turley","year":"2011","journal-title":"Vaccine"},{"key":"ref_185","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\u2013Flagellin Fusion Vaccine (VAX125, STF2.HA1 SI)","volume":"29","author":"Taylor","year":"2011","journal-title":"Vaccine"},{"key":"ref_186","doi-asserted-by":"crossref","unstructured":"Holmgren, J. (2021). An Update on Cholera Immunity and Current and Future Cholera Vaccines. Trop. Med. Infect. Dis., 6.","DOI":"10.3390\/tropicalmed6020064"},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1111\/j.1365-2249.2004.02520.x","article-title":"Oral Tolerization with Peptide 336\u2013351 Linked to Cholera Toxin B Subunit in Preventing Relapses of Uveitis in Behcet\u2019s Disease","volume":"137","author":"Stanford","year":"2004","journal-title":"Clin. Exp. Immunol."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.1016\/j.vaccine.2019.11.047","article-title":"A Double-Blind, Randomized Controlled Trial to Evaluate the Safety and Immunogenicity of an Intranasally Administered Trivalent Inactivated Influenza Vaccine with the Adjuvant LTh(\u03b1K): A Phase II Study","volume":"38","author":"Pan","year":"2020","journal-title":"Vaccine"},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"713769","DOI":"10.1155\/2011\/713769","article-title":"Bacterial Toxin Fusion Proteins Elicit Mucosal Immunity against a Foot-and-Mouth Disease Virus Antigen When Administered Intranasally to Guinea Pigs","volume":"2011","author":"Challa","year":"2011","journal-title":"Adv. Virol."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"148","DOI":"10.3390\/vaccines3010148","article-title":"Choice and Design of Adjuvants for Parenteral and Mucosal Vaccines","volume":"3","author":"Savelkoul","year":"2015","journal-title":"Vaccines"},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/S1473-3099(19)30571-7","article-title":"Safety and Immunogenicity of the Oral, Inactivated, Enterotoxigenic Escherichia coli Vaccine ETVAX in Bangladeshi Children and Infants: A Double-Blind, Randomised, Placebo-Controlled Phase 1\/2 Trial","volume":"20","author":"Qadri","year":"2020","journal-title":"Lancet Infect. Dis."},{"key":"ref_192","first-page":"473","article-title":"The Human Primary Immune Response to Keyhole Limpet Haemocyanin: Interrelationships of Delayed Hypersensitivity, Antibody Response and In Vitro Blast Transformation","volume":"6","author":"Curtis","year":"1970","journal-title":"Clin. Exp. Immpunol."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/0019-2791(64)90030-8","article-title":"Immunochemical Properties of Hemocyanin","volume":"1","author":"Weigle","year":"1964","journal-title":"Immunochemistry"},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1056\/NEJM196707272770401","article-title":"Immunosuppressive Therapy: The Relation between Clinical Response and Immunologic Competence","volume":"277","author":"Swanson","year":"1967","journal-title":"N. Engl. J. Med."},{"key":"ref_195","first-page":"236","article-title":"Hemocyanins as Immunostimulants","volume":"139","author":"Arancibia","year":"2010","journal-title":"Rev. Med. Chile"},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1111\/bcp.12422","article-title":"Keyhole Limpet Haemocyanin\u2014A Model Antigen for Human Immunotoxicological Studies: KLH as Neoantigen in Human Immunotoxicological Studies","volume":"78","author":"Swaminathan","year":"2014","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/S0022-5347(17)59919-X","article-title":"Immunologic Reduction of Bladder Cancer Recurrence Rate","volume":"111","author":"Olsson","year":"1974","journal-title":"J. Urol."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1016\/S0022-5347(17)42610-3","article-title":"Immunotherapy in Bladder Cancer with Keyhole-Limpet Hemocyanin: A Randomized Study","volume":"139","author":"Jurincic","year":"1988","journal-title":"J. Urol."},{"key":"ref_199","unstructured":"(2022, June 14). Results for KLH at ClinicalTrials.Gov, Available online: https:\/\/clinicaltrials.gov\/ct2\/results?term=KLH."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"2977","DOI":"10.1158\/1078-0432.CCR-06-2189","article-title":"Immunization of High-Risk Breast Cancer Patients with Clustered sTn-KLH Conjugate plus the Immunologic Adjuvant QS-21","volume":"13","author":"Gilewski","year":"2007","journal-title":"Clin. Cancer Res."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1634\/theoncologist.2010-0307","article-title":"Phase III Multicenter Clinical Trial of the Sialyl-TN (STn)-Keyhole Limpet Hemocyanin (KLH) Vaccine for Metastatic Breast Cancer","volume":"16","author":"Miles","year":"2011","journal-title":"Oncologist"},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1002\/(SICI)1097-0215(20000301)85:5<659::AID-IJC11>3.0.CO;2-5","article-title":"Induction of Antibodies against GD3 Ganglioside in Melanoma Patients by Vaccination with GD3-Lactone-KLH Conjugate Plus Immunological Adjuvant QS-21","volume":"85","author":"Ragupathi","year":"2000","journal-title":"Int. J. Cancer"},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"3831","DOI":"10.1200\/JCO.2012.47.9303","article-title":"Adjuvant Ganglioside GM2-KLH\/QS-21 Vaccination Versus Observation After Resection of Primary Tumor > 1.5 mm in Patients with Stage II Melanoma: Results of the EORTC 18961 Randomized Phase III Trial","volume":"31","author":"Eggermont","year":"2013","journal-title":"J. Clin. Oncol."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1158\/1078-0432.CCR-03-0101","article-title":"Vaccination of Small Cell Lung Cancer Patients with Polysialic Acid or N-Propionylated Polysialic Acid Conjugated to Keyhole Limpet Hemocyanin","volume":"10","author":"Krug","year":"2004","journal-title":"Clin. Cancer Res."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1007\/s00262-011-1083-6","article-title":"Immunization with N-Propionyl Polysialic Acid\u2013KLH Conjugate in Patients with Small Cell Lung Cancer Is Safe and Induces IgM Antibodies Reactive with SCLC Cells and Bactericidal against Group B Meningococci","volume":"61","author":"Krug","year":"2012","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1016\/j.intimp.2008.03.008","article-title":"Modulation of the Immune Response Using Rapana thomasiana Hemocyanin","volume":"8","author":"Tchorbanov","year":"2008","journal-title":"Int. Immunopharmacol."},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"R3","DOI":"10.1007\/BF01470992","article-title":"Marine Tumor Vaccine Carriers: Structure of the Molluscan Hemocyanins KLH and HtH","volume":"127","author":"Markl","year":"2001","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1046\/j.1432-1327.1999.00564.x","article-title":"Abalone (Haliotis tuberculata) Hemocyanin Type 1 (HtH1). Organization of the \u2248 400 kDa Subunit, and Amino Acid Sequence of Its Functional Units f, g and h","volume":"264","author":"Keller","year":"1999","journal-title":"Eur. J. Biochem."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"1488","DOI":"10.1038\/bjc.2013.494","article-title":"Tumour Cell Lysate-Loaded Dendritic Cell Vaccine Induces Biochemical and Memory Immune Response in Castration-Resistant Prostate Cancer Patients","volume":"109","author":"Reyes","year":"2013","journal-title":"Br. J. Cancer"},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1097\/CJI.0b013e3181facf48","article-title":"Induction of Cellular Immune Responses in Patients with Stage-I Multiple Myeloma After Vaccination with Autologous Idiotype-pulsed Dendritic Cells","volume":"34","author":"Schmidt","year":"2011","journal-title":"J. Immunother."},{"key":"ref_211","doi-asserted-by":"crossref","unstructured":"Langlais, C., and Korn, B. (2006). Recombinant Protein Expression in Bacteria. Encyclopedic Reference of Genomics and Proteomics in Molecular Medicine, Springer.","DOI":"10.1007\/3-540-29623-9_4800"},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"10457","DOI":"10.1007\/s00253-018-9430-6","article-title":"Glycosylation Control Technologies for Recombinant Therapeutic Proteins","volume":"102","author":"Gupta","year":"2018","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/S0167-7799(97)01155-4","article-title":"Strategies for Optimizing Heterologous Protein Expression in Escherichia coli","volume":"16","author":"Hannig","year":"1998","journal-title":"Trends Biotechnol."},{"key":"ref_214","first-page":"257","article-title":"Expression and Purification of Recombinant Proteins Using the PET System","volume":"13","author":"Mierendorf","year":"1998","journal-title":"Methods Mol. Med."},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/0022-2836(86)90385-2","article-title":"Use of Bacteriophage T7 RNA Polymerase to Direct Selective High-Level Expression of Cloned Genes","volume":"189","author":"Studier","year":"1986","journal-title":"J. Mol. Biol."},{"key":"ref_216","unstructured":"Boisgu\u00e9rin, V. (2006). Recombinant Expression of Molluscan Hemocyanin (KLH) Substructures in a Prokaryotic System: E. Coli. [Ph.D. Dissertation, Johannes Gutenberg-Universit\u00e4t]."},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"5677","DOI":"10.4049\/jimmunol.1002156","article-title":"Flagellin as an Adjuvant: Cellular Mechanisms and Potential","volume":"185","author":"Mizel","year":"2010","journal-title":"J. Immunol."},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1016\/j.vaccine.2018.12.009","article-title":"Recombinant Flagellins with Deletions in Domains D1, D2, and D3: Characterization as Novel Immunoadjuvants","volume":"37","author":"Biedma","year":"2019","journal-title":"Vaccine"},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.4014\/jmb.0812.675","article-title":"Overexpression, Purification, and Immunogenicity of Recombinant Porin Proteins of Salmonella enterica Serovar Typhi (S. typhi)","volume":"19","author":"Verma","year":"2009","journal-title":"J. Microbiol. Biotechnol."},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1128\/IAI.74.1.586-593.2006","article-title":"Construction and Immunological Characterization of a Novel Nontoxic Protective Pneumolysin Mutant for Use in Future Pneumococcal Vaccines","volume":"74","author":"Kirkham","year":"2006","journal-title":"Infect. Immun."},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"1666","DOI":"10.1128\/IAI.01391-13","article-title":"Mucosal Immunization with Recombinant Fusion Protein DnaJ-\u0394A146Ply Enhances Cross-Protective Immunity against Streptococcus pneumoniae Infection in Mice via Interleukin 17A","volume":"82","author":"Liu","year":"2014","journal-title":"Infect. Immun."},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.1586\/14760584.2015.1081067","article-title":"Effect of Vaccine Administration Modality on Immunogenicity and Efficacy","volume":"14","author":"Zhang","year":"2015","journal-title":"Expert Rev. Vaccines"},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1517\/17425247.3.6.747","article-title":"Delivery Systems and Adjuvants for Oral Vaccines","volume":"3","author":"Lavelle","year":"2006","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"645210","DOI":"10.3389\/fimmu.2021.645210","article-title":"Vaccine Inoculation Route Modulates Early Immunity and Consequently Antigen-Specific Immune Response","volume":"12","author":"Rosenbaum","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_225","unstructured":"World Health Organization (2014). Guidelines on the Nonclinical Evaluation of Vaccine Adjuvants and Adjuvanted Vaccines, WHO. Annex 2, TRS No. 987."},{"key":"ref_226","doi-asserted-by":"crossref","unstructured":"Gruber, M.F., and Marshall, V.B. (2018). Regulation and Testing of Vaccines. Plotkin\u2019s Vaccines, Elsevier.","DOI":"10.1016\/B978-0-323-35761-6.00079-1"},{"key":"ref_227","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1038\/s41598-017-00555-4","article-title":"The TLR2 Binding Neisserial Porin PorB Enhances Antigen Presenting Cell Trafficking and Cross-Presentation","volume":"7","author":"Reiser","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"749","DOI":"10.2217\/fmb.10.41","article-title":"Innate Immune Function of the Neisserial Porins and the Relationship to Vaccine Adjuvant Activity","volume":"5","author":"Wetzler","year":"2010","journal-title":"Future Microbiol."},{"key":"ref_229","doi-asserted-by":"crossref","unstructured":"Anderson, J.M. (2012). Biocompatibility. Polymer Science: A Comprehensive Reference, Elsevier.","DOI":"10.1016\/B978-0-444-53349-4.00229-6"},{"key":"ref_230","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/0264-410X(93)90190-9","article-title":"Adjuvants\u2014A Balance between Toxicity and Adjuvanticity","volume":"11","author":"Gupta","year":"1993","journal-title":"Vaccine"},{"key":"ref_231","doi-asserted-by":"crossref","unstructured":"Balaji, A.B., Pakalapati, H., Khalid, M., Walvekar, R., and Siddiqui, H. (2018). Natural and Synthetic Biocompatible and Biodegradable Polymers. Biodegradable and Biocompatible Polymer Composites, Elsevier.","DOI":"10.1016\/B978-0-08-100970-3.00001-8"},{"key":"ref_232","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1111\/j.1574-695X.2008.00460.x","article-title":"Bordetella pertussis Filamentous Hemagglutinin Delivered by Mucosal Routes Enhances Immunoglobulin Levels in Serum and Mucosal Fluids","volume":"54","author":"Vendeville","year":"2008","journal-title":"FEMS Microbiol. Immunol."},{"key":"ref_233","doi-asserted-by":"crossref","unstructured":"Pasquevich, K.A., Iba\u00f1ez, A.E., Coria, L.M., Samartino, C.G., Estein, S.M., Zwerdling, A., Barrionuevo, P., Oliveira, F.S., Seither, C., and Warzecha, H. (2011). An Oral Vaccine Based on U-Omp19 Induces Protection against B. Abortus Mucosal Challenge by Inducing an Adaptive IL-17 Immune Response in Mice. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0016203"},{"key":"ref_234","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1016\/j.biopha.2018.06.026","article-title":"Efficacy and Safety of Immunological Adjuvants. Where Is the Cut-Off?","volume":"105","author":"Carlos","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_235","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_236","doi-asserted-by":"crossref","unstructured":"Wang, Z.-B., and Xu, J. (2020). Better Adjuvants for Better Vaccines: Progress in Adjuvant Delivery Systems, Modifications, and Adjuvant\u2013Antigen Codelivery. Vaccines, 8.","DOI":"10.3390\/vaccines8010128"},{"key":"ref_237","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1080\/03079450600597873","article-title":"Genetic Detoxification and Adjuvant-Activity Retention of Escherichia coli Enterotoxin LT","volume":"35","author":"Vasserman","year":"2006","journal-title":"Avian Pathol."},{"key":"ref_238","doi-asserted-by":"crossref","first-page":"2171","DOI":"10.3389\/fimmu.2020.02171","article-title":"Immunogenicity and Toxicity of Different Adjuvants Can Be Characterized by Profiling Lung Biomarker Genes After Nasal Immunization","volume":"11","author":"Sasaki","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_239","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.jbiotec.2014.01.037","article-title":"In Silico and In Vivo Studies of Truncated Forms of Flagellin (FliC) of Enteroaggregative Escherichia coli Fused to FimH from Uropathogenic Escherichia coli as a Vaccine Candidate against Urinary Tract Infections","volume":"175","author":"Savar","year":"2014","journal-title":"J. Biotechnol."},{"key":"ref_240","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1038\/nrmicro1681","article-title":"The Perfect Mix: Recent Progress in Adjuvant Research","volume":"5","author":"Guy","year":"2007","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_241","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1016\/j.vaccine.2006.08.013","article-title":"Vaccination with Recombinant Fusion Proteins Incorporating Toll-like Receptor Ligands Induces Rapid Cellular and Humoral Immunity","volume":"25","author":"Huleatt","year":"2007","journal-title":"Vaccine"},{"key":"ref_242","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1038\/s41541-021-00294-8","article-title":"Vaccines for Human Fungal Diseases: Close but Still a Long Way to Go","volume":"6","author":"Oliveira","year":"2021","journal-title":"NPJ Vaccines"},{"key":"ref_243","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.imlet.2015.05.010","article-title":"Endotoxin-Minimized HIV-1 P24 Fused to Murine Hsp70 Activates Dendritic Cells, Facilitates Endocytosis and P24-Specific Th1 Response in Mice","volume":"166","author":"Krupka","year":"2015","journal-title":"Immunol. Lett."},{"key":"ref_244","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1186\/1479-5876-11-300","article-title":"Fusion of Hsp70 to Mage-A1 Enhances the Potency of Vaccine-Specific Immune Responses","volume":"11","author":"Jiang","year":"2013","journal-title":"J. Transl. Med."},{"key":"ref_245","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.imlet.2005.09.004","article-title":"Prophylactic, Therapeutic and Anti-Metastatic Effects of an HPV-16mE6\u0394\/ME7\/TBhsp70\u0394 Fusion Protein Vaccine in an Animal Model","volume":"102","author":"Qian","year":"2006","journal-title":"Immunol. Lett."},{"key":"ref_246","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1128\/IAI.66.4.1513-1520.1998","article-title":"Enhanced Protective Antibody Responses to PspA after Intranasal or Subcutaneous Injections of PspA Genetically Fused to Granulocyte-Macrophage Colony-Stimulating Factor or Interleukin-2","volume":"66","author":"Wortham","year":"1998","journal-title":"Infect. Immun."},{"key":"ref_247","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1016\/j.intimp.2015.02.030","article-title":"Molecular Attributes of Conjugate Antigen Influence Function of Antibodies Induced by Anti-Nicotine Vaccine in Mice and Non-Human Primates","volume":"25","author":"McCluskie","year":"2015","journal-title":"Int. Immunopharmacol."},{"key":"ref_248","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1021\/ar5004187","article-title":"Development of Globo-H Cancer Vaccine","volume":"48","author":"Danishefsky","year":"2015","journal-title":"Acc. Chem. Res."},{"key":"ref_249","doi-asserted-by":"crossref","first-page":"3371","DOI":"10.4049\/jimmunol.179.5.3371","article-title":"B Subunit of Shiga Toxin-Based Vaccines Synergize with \u03b1-Galactosylceramide to Break Tolerance against Self Antigen and Elicit Antiviral Immunity","volume":"179","author":"Adotevi","year":"2007","journal-title":"J. Immunol."},{"key":"ref_250","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1016\/j.intimp.2007.04.012","article-title":"Immunization Prevents DDT Buildup in Mouse Tissues","volume":"7","author":"Hrafnkelsdottir","year":"2007","journal-title":"Int. Immunopharmacol."},{"key":"ref_251","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.intimp.2013.03.021","article-title":"Enhancing Immunogenicity of a 3\u2032aminomethylnicotine-DT-Conjugate Anti-Nicotine Vaccine with CpG Adjuvant in Mice and Non-Human Primates","volume":"16","author":"McCluskie","year":"2013","journal-title":"Int. Immunopharmacol."},{"key":"ref_252","doi-asserted-by":"crossref","unstructured":"Thorn, J.M., Bhattacharya, K., Crutcher, R., Sperry, J., Isele, C., Kelly, B., Yates, L., Zobel, J., Zhang, N., and Davis, H.L. (2017). The Effect of Physicochemical Modification on the Function of Antibodies Induced by Anti-Nicotine Vaccine in Mice. Vaccines, 5.","DOI":"10.3390\/vaccines5020011"},{"key":"ref_253","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.jconrel.2019.11.018","article-title":"Semisynthetic, Self-Adjuvanting Vaccine Development: Efficient, Site-Specific Sortase A-Mediated Conjugation of Toll-like Receptor 2 Ligand FSL-1 to Recombinant Protein Antigens under Native Conditions and Application to a Model Group A Streptococcal Vaccine","volume":"317","author":"Xu","year":"2020","journal-title":"J. Control. Release"},{"key":"ref_254","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1186\/s12951-017-0289-y","article-title":"A Versatile Papaya Mosaic Virus (PapMV) Vaccine Platform Based on Sortase-Mediated Antigen Coupling","volume":"15","author":"Carignan","year":"2017","journal-title":"J. Nanobiotechnol."},{"key":"ref_255","doi-asserted-by":"crossref","unstructured":"Lalibert\u00e9-Gagn\u00e9, M.\u00c8., Bolduc, M., Th\u00e9rien, A., Garneau, C., Casault, P., Savard, P., Estaquier, J., and Leclerc, D. (2019). Increased Immunogenicity of Full-Length Protein Antigens through Sortase-Mediated Coupling on the PapMV Vaccine Platform. Vaccines, 7.","DOI":"10.3390\/vaccines7020049"},{"key":"ref_256","doi-asserted-by":"crossref","first-page":"10834","DOI":"10.1021\/nn404211j","article-title":"Engineering an Effective Immune Adjuvant by Designed Control of Shape and Crystallinity of Aluminum Oxyhydroxide Nanoparticles","volume":"7","author":"Sun","year":"2013","journal-title":"ACS Nano"},{"key":"ref_257","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.jconrel.2013.10.032","article-title":"Aluminum Hydroxide Nanoparticles Show a Stronger Vaccine Adjuvant Activity than Traditional Aluminum Hydroxide Microparticles","volume":"173","author":"Li","year":"2014","journal-title":"J. Control. Release"},{"key":"ref_258","doi-asserted-by":"crossref","first-page":"1700426","DOI":"10.1002\/advs.201700426","article-title":"Turning the Old Adjuvant from Gel to Nanoparticles to Amplify CD8+ T Cell Responses","volume":"5","author":"Jiang","year":"2018","journal-title":"Adv. Sci."},{"key":"ref_259","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1038\/nri3547","article-title":"Age-Dependent Dysregulation of Innate Immunity","volume":"13","author":"Shaw","year":"2013","journal-title":"Nat. Rev. Immunol."},{"key":"ref_260","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/j.immuni.2006.05.001","article-title":"Aging of the Immune System: How Much Can the Adaptive Immune System Adapt?","volume":"24","author":"Weng","year":"2006","journal-title":"Immunity"},{"key":"ref_261","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/j.arr.2010.10.008","article-title":"Influenza Vaccine Responses in Older Adults","volume":"10","author":"McElhaney","year":"2011","journal-title":"Ageing Res. Rev."},{"key":"ref_262","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1016\/S0140-6736(05)67339-4","article-title":"Efficacy and Effectiveness of Influenza Vaccines in Elderly People: A Systematic Review","volume":"366","author":"Jefferson","year":"2005","journal-title":"Lancet"},{"key":"ref_263","doi-asserted-by":"crossref","first-page":"2518","DOI":"10.4049\/jimmunol.0901022","article-title":"Age-Associated Decrease in TLR Function in Primary Human Dendritic Cells Predicts Influenza Vaccine Response","volume":"184","author":"Panda","year":"2010","journal-title":"J. Immunol."},{"key":"ref_264","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1111\/j.1474-9726.2011.00759.x","article-title":"Age-Associated Elevation in TLR5 Leads to Increased Inflammatory Responses in the Elderly","volume":"11","author":"Qian","year":"2012","journal-title":"Aging Cell"},{"key":"ref_265","doi-asserted-by":"crossref","first-page":"8147","DOI":"10.1016\/j.vaccine.2011.08.027","article-title":"Efficacy of a Vaccine That Links Viral Epitopes to Flagellin in Protecting Aged Mice from Influenza Viral Infection","volume":"29","author":"Leng","year":"2011","journal-title":"Vaccine"},{"key":"ref_266","doi-asserted-by":"crossref","first-page":"e00094-21","DOI":"10.1128\/CMR.00094-21","article-title":"Pathogenesis of Respiratory Viral and Fungal Coinfections","volume":"35","author":"Salazar","year":"2022","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_267","doi-asserted-by":"crossref","first-page":"2456","DOI":"10.1080\/21645515.2016.1181236","article-title":"Mucosal Adjuvants: Opportunities and Challenges: An Overview of Novel Adjuvants Designed for Improving Vaccine Efficacy","volume":"12","author":"Zeng","year":"2016","journal-title":"Hum. Vaccines Immunother."},{"key":"ref_268","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1016\/j.tips.2017.06.002","article-title":"An Overview of Novel Adjuvants Designed for Improving Vaccine Efficacy","volume":"38","author":"Bonam","year":"2017","journal-title":"Trends Pharmacol. Sci."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/14\/8\/1671\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:07:23Z","timestamp":1760141243000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/14\/8\/1671"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,11]]},"references-count":268,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2022,8]]}},"alternative-id":["pharmaceutics14081671"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics14081671","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,11]]}}}