{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T03:27:01Z","timestamp":1776482821363,"version":"3.51.2"},"reference-count":61,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2020,1,13]],"date-time":"2020-01-13T00:00:00Z","timestamp":1578873600000},"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","doi-asserted-by":"publisher","award":["1132975"],"award-info":[{"award-number":["1132975"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Group A Streptococcus (GAS)-associated rheumatic heart disease is a leading cause of death caused by GAS infection. While antibiotics can treat the infection in most cases, growing antibiotic resistance, late medical intervention, and recurrent infection are major obstacles to the effective treatment of GAS-associated diseases. As GAS infection typically originates from the bacterial colonization of mucosal tissue in the throat, an oral vaccine that can generate both systemic and mucosal immune responses would solve problems associated with traditional medical interventions. Moreover, orally delivered vaccines are more easily administered and less expensive for mass immunization. In this study, the B-cell epitope J8, derived from GAS M protein, and universal T-helper Pan HLA-DR-binding epitope peptide (PADRE), were conjugated to poly (methyl acrylate) (PMA) to form a self-assembled nanoparticle vaccine candidate (PMA-P-J8). Strong systemic and mucosal immune responses were induced upon single oral immunization of mice with the conjugate. The antibodies generated were opsonic against GAS clinical isolates as measured after boost immunization. Thus, we developed a simple conjugate as an effective, adjuvant-free oral peptide-based vaccine.<\/jats:p>","DOI":"10.3390\/vaccines8010023","type":"journal-article","created":{"date-parts":[[2020,1,15]],"date-time":"2020-01-15T03:20:22Z","timestamp":1579058422000},"page":"23","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Polyacrylate\u2013Peptide Antigen Conjugate as a Single-Dose Oral Vaccine against Group A Streptococcus"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3932-3515","authenticated-orcid":false,"given":"Mohammad Omer","family":"Faruck","sequence":"first","affiliation":[{"name":"School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, Brisbane, QLD 4072, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lili","family":"Zhao","sequence":"additional","affiliation":[{"name":"School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, Brisbane, QLD 4072, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Waleed M.","family":"Hussein","sequence":"additional","affiliation":[{"name":"School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, Brisbane, QLD 4072, Australia"},{"name":"Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Helwan University, Helwan 11795, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zeinab G.","family":"Khalil","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4072, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8341-7754","authenticated-orcid":false,"given":"Robert J.","family":"Capon","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4072, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7257-807X","authenticated-orcid":false,"given":"Mariusz","family":"Skwarczynski","sequence":"additional","affiliation":[{"name":"School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, Brisbane, QLD 4072, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Istvan","family":"Toth","sequence":"additional","affiliation":[{"name":"School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, Brisbane, 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, Brisbane, QLD 4102, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,1,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1038\/nrd2224","article-title":"More than one reason to rethink the use of peptides in vaccine design","volume":"6","author":"Purcell","year":"2007","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_2","unstructured":"Koutsopoulos, S. (2018). Peptide-based vaccines. Peptide Applications in Biomedicine, Biotechnology and Bioengineering, Woodhead Publishing."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1038\/nchembio.1383","article-title":"Designing immunogenic peptides","volume":"9","author":"Flower","year":"2013","journal-title":"Nat. Chem. Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1039\/C5SC03892H","article-title":"Peptide-based synthetic vaccines","volume":"7","author":"Skwarczynski","year":"2016","journal-title":"Chem. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"778","DOI":"10.4161\/hv.27332","article-title":"Recent progress in adjuvant discovery for peptide-based subunit vaccines","volume":"10","author":"Azmi","year":"2014","journal-title":"Hum. Vaccines Immunother."},{"key":"ref_6","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_7","doi-asserted-by":"crossref","unstructured":"Zheng, J., Gao, S., Cui, X., Sun, D., and Zhao, K. (2019). Adjuvants and delivery systems based on polymeric nanoparticles for mucosal vaccines. Int. J. Pharm., 118731.","DOI":"10.1016\/j.ijpharm.2019.118731"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1080\/21645515.2016.1239668","article-title":"Current prospects and future challenges for nasal vaccine delivery","volume":"13","author":"Yusuf","year":"2017","journal-title":"Hum. Vaccines Immunother."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.addr.2017.04.008","article-title":"Current state and challenges in developing oral vaccines","volume":"114","author":"Sharpe","year":"2017","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1586\/14760584.2014.936852","article-title":"Oral delivery of nanoparticle-based vaccines","volume":"13","author":"Marasini","year":"2014","journal-title":"Expert Rev. Vaccines"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1097\/QCO.0b013e3283458f7e","article-title":"New understandings in Streptococcus pyogenes","volume":"24","author":"Lynskey","year":"2011","journal-title":"Curr. Opin. Infect. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1016\/S1473-3099(05)70267-X","article-title":"The global burden of group A streptococcal diseases","volume":"5","author":"Carapetis","year":"2005","journal-title":"Lancet Infect. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1128\/CMR.13.3.470","article-title":"Pathogenesis of group A streptococcal infections","volume":"13","author":"Cunningham","year":"2000","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_14","unstructured":"Sanyahumbi, A.S., Colquhoun, S., Wyber, R., and Carapetis, J.R. (2019, December 12). Global disease burden of group A Streptococcus, Streptococcus Pyogenes: Basic Biology to Clinical Manifestations [Internet], Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK333415\/."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.1016\/j.amjcard.2010.01.364","article-title":"Prevalence of Rheumatic Heart Disease in Children and Young Adults in Nicaragua","volume":"105","author":"Paar","year":"2010","journal-title":"Am. J. Cardiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1056\/NEJMoa1603693","article-title":"Global, Regional, and National Burden of Rheumatic Heart Disease, 1990\u20132015","volume":"377","author":"Watkins","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1038\/nrcardio.2009.162","article-title":"Prevention and treatment of rheumatic heart disease in the developing world","volume":"6","author":"Steer","year":"2009","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1053\/j.spid.2006.07.001","article-title":"Group A Streptococcus","volume":"17","author":"Martin","year":"2006","journal-title":"Semin. Pediatr. Infect. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2953","DOI":"10.1016\/j.vaccine.2016.03.073","article-title":"Status of research and development of vaccines for Streptococcus pyogenes","volume":"34","author":"Steer","year":"2016","journal-title":"Vaccine"},{"key":"ref_20","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_21","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1097\/QCO.0b013e328332bbfe","article-title":"Group A streptococcal vaccines: Facts versus fantasy","volume":"22","author":"Steer","year":"2009","journal-title":"Curr. Opin. Infect. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1365-2958.2005.04967.x","article-title":"Domains of group A streptococcal M protein that confer resistance to phagocytosis, opsonization and protection: Implications for vaccine development","volume":"59","author":"McArthur","year":"2006","journal-title":"Mol. Microbiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/S0020-7519(01)00360-5","article-title":"Adapting immunity with subunit vaccines: Case studies with group A Streptococcus and malaria","volume":"32","author":"Good","year":"2002","journal-title":"Int. J. Parasitol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1038\/74719","article-title":"New multi-determinant strategy for a group A streptococcal vaccine designed for the Australian Aboriginal population","volume":"6","author":"Brandt","year":"2000","journal-title":"Nat. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"E222","DOI":"10.1111\/1469-0691.12134","article-title":"Updated model of group A Streptococcus M proteins based on a comprehensive worldwide study","volume":"19","author":"McMillan","year":"2013","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1093\/intimm\/6.8.1235","article-title":"Identification of T cell autoepitopes that cross-react with the C-terminal segment of the M protein of group A streptococci","volume":"6","author":"Pruksakorn","year":"1994","journal-title":"Int. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1016\/S0140-6736(94)92083-4","article-title":"Towards a vaccine for rheumatic fever: Identification of a conserved target epitope on M protein of group A streptococci","volume":"344","author":"Pruksakorn","year":"1994","journal-title":"Lancet"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Sekuloski, S., Batzloff, M.R., Griffin, P., Parsonage, W., Elliott, S., Hartas, J., O\u2018Rourke, P., Marquart, L., Pandey, M., and Rubin, F.A. (2018). Evaluation of safety and immunogenicity of a group A streptococcus vaccine candidate (MJ8VAX) in a randomized clinical trial. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0198658"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"13786","DOI":"10.1038\/s41598-017-14157-7","article-title":"Physicochemical characterisation, immunogenicity and protective efficacy of a lead streptococcal vaccine: Progress towards Phase I trial","volume":"7","author":"Pandey","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1086\/505580","article-title":"Intranasal administration is an effective mucosal vaccine delivery route for self-adjuvanting lipid core peptides targeting the group A streptococcal M protein","volume":"194","author":"Olive","year":"2006","journal-title":"J. Infect. Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2635","DOI":"10.1016\/S0264-410X(02)00206-2","article-title":"Parenteral and mucosal delivery of a novel multi-epitope M protein-based group A streptococcal vaccine construct: Investigation of immunogenicity in mice","volume":"20","author":"Dunn","year":"2002","journal-title":"Vaccine"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.2217\/nnm.16.36","article-title":"Multilayer engineered nanoliposomes as a novel tool for oral delivery of lipopeptide-based vaccines against group A Streptococcus","volume":"11","author":"Marasini","year":"2016","journal-title":"Nanomedicine"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"183","DOI":"10.33218\/prnano1(3).181003.1","article-title":"Liposomal formulation of polyacrylate-peptide conjugate as a new vaccine candidate against cervical cancer","volume":"1","author":"Khongkow","year":"2018","journal-title":"Prec. Nanomed."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"601","DOI":"10.4155\/tde-2016-0037","article-title":"Linear and branched polyacrylates as a delivery platform for peptide-based vaccines","volume":"7","author":"Chandrudu","year":"2016","journal-title":"Ther. Deliv."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4372","DOI":"10.1016\/j.bmc.2016.07.036","article-title":"Multiantigenic peptide-polymer conjugates as therapeutic vaccines against cervical cancer","volume":"24","author":"Hussein","year":"2016","journal-title":"Bioorg. Med. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3","DOI":"10.2174\/1567201811666141001155729","article-title":"Self-Adjuvanting Therapeutic Peptide-Based Vaccine Induce CD8+ Cytotoxic T Lymphocyte Responses in a Murine Human Papillomavirus Tumor Model","volume":"12","author":"Liu","year":"2015","journal-title":"Curr. Drug Deliv."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1021\/jm501514h","article-title":"Polyacrylate-Based Delivery System for Self-adjuvanting Anticancer Peptide Vaccine","volume":"58","author":"Liu","year":"2015","journal-title":"J. Med. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"35","DOI":"10.2217\/nnm.13.7","article-title":"Polymer-peptide hybrids as a highly immunogenic single-dose nanovaccine","volume":"9","author":"Fuaad","year":"2014","journal-title":"Nanomedicine"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.nano.2010.10.002","article-title":"Self-adjuvanting polyacrylic nanoparticulate delivery system for group A streptococcus (GAS) vaccine","volume":"7","author":"Zaman","year":"2011","journal-title":"Nanomed. Nanotechnol. Biol. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"5742","DOI":"10.1002\/anie.201002221","article-title":"Polyacrylate Dendrimer Nanoparticles: A Self-Adjuvanting Vaccine Delivery System","volume":"49","author":"Skwarczynski","year":"2010","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3223","DOI":"10.2217\/nnm-2016-0291","article-title":"Double adjuvanting strategy for peptide-based vaccines: Trimethyl chitosan nanoparticles for lipopeptide delivery","volume":"11","author":"Marasini","year":"2016","journal-title":"Nanomedicine"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1007\/978-1-4939-3387-7_36","article-title":"The Use of Microwave-Assisted Solid-Phase Peptide Synthesis and Click Chemistry for the Synthesis of Vaccine Candidates Against Hookworm Infection","volume":"1403","author":"Skwarczynski","year":"2016","journal-title":"Methods Mol. Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.eurpolymj.2019.03.009","article-title":"Polymers for subunit vaccine delivery","volume":"114","author":"Nevagi","year":"2019","journal-title":"Eur. Polym. J."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.actbio.2014.11.050","article-title":"Effective polymer adjuvants for sustained delivery of protein subunit vaccines","volume":"14","author":"Adams","year":"2015","journal-title":"Acta Biomater."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Sahdev, P., Ochyl, L.J., and Moon, J.J. (2014). Biomaterials for Nanoparticle Vaccine Delivery Systems. Pharm. Res., 2563\u20132582.","DOI":"10.1007\/s11095-014-1419-y"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2657","DOI":"10.2217\/nnm.14.187","article-title":"Recent advances in peptide-based subunit nanovaccines","volume":"9","author":"Skwarczynski","year":"2014","journal-title":"Nanomedicine"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"4937","DOI":"10.1021\/acsbiomaterials.9b01135","article-title":"Polyelectrolyte-Based Platforms for the Delivery of Peptides and Proteins","volume":"5","author":"Zhao","year":"2019","journal-title":"ACS Biomater. Sci. Eng."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.2174\/1568026614666140329232757","article-title":"Liposomes as nanovaccine delivery systems","volume":"14","author":"Ghaffar","year":"2014","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1080\/10611860410001670017","article-title":"Immunological aspects of polymer microsphere vaccine delivery systems","volume":"11","author":"Eyles","year":"2003","journal-title":"J. Drug Target."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"117","DOI":"10.2174\/187221107780831897","article-title":"Recent developments in particulate-based vaccines","volume":"1","author":"Perrie","year":"2007","journal-title":"Recent Pat. Drug Deliv. Formul."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1158\/2326-6066.CIR-18-0166","article-title":"Nanoparticle Conjugation of Human Papillomavirus 16 E7-long Peptides Enhances Therapeutic Vaccine Efficacy against Solid Tumors in Mice","volume":"6","author":"Galliverti","year":"2018","journal-title":"Cancer Immunol. Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/j.actbio.2018.09.037","article-title":"Polyglutamic acid-trimethyl chitosan-based intranasal peptide nano-vaccine induces potent immune responses against group A streptococcus","volume":"80","author":"Nevagi","year":"2018","journal-title":"Acta Biomater."},{"key":"ref_53","first-page":"18","article-title":"Self-assembled peptide-polymer conjugates as vaccines","volume":"32","author":"Liu","year":"2014","journal-title":"Chim. Oggi."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1038\/s41563-018-0256-5","article-title":"Antigens reversibly conjugated to a polymeric glyco-adjuvant induce protective humoral and cellular immunity","volume":"18","author":"Wilson","year":"2019","journal-title":"Nat. Mater."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1625","DOI":"10.4049\/jimmunol.164.3.1625","article-title":"Linear PADRE T helper epitope and carbohydrate B cell epitope conjugates induce specific high titer IgG antibody responses","volume":"164","author":"Alexander","year":"2000","journal-title":"J. Immunol."},{"key":"ref_56","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_57","doi-asserted-by":"crossref","first-page":"2798","DOI":"10.1021\/bm400626w","article-title":"Self-Adjuvanting Polymer-Peptide Conjugates As Therapeutic Vaccine Candidates against Cervical Cancer","volume":"14","author":"Liu","year":"2013","journal-title":"Biomacromolecules"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1111\/j.1365-2567.2006.02368.x","article-title":"Oral tolerance induction by mucosal administration of cholera toxin B-coupled antigen involves T-cell proliferation in vivo and is not affected by depletion of CD25(+) T cells","volume":"118","author":"Chandy","year":"2006","journal-title":"Immunology"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"8278","DOI":"10.4049\/jimmunol.181.12.8278","article-title":"B Lymphocytes Promote Expansion of Regulatory T Cells in Oral Tolerance: Powerful Induction by Antigen Coupled to Cholera Toxin B Subunit","volume":"181","author":"Sun","year":"2008","journal-title":"J. Immunol."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Stratmann, T. (2015). Cholera Toxin Subunit B as Adjuvant\u2014An Accelerator in Protective Immunity and a Break in Autoimmunity. Vaccines, 3.","DOI":"10.3390\/vaccines3030579"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Bartlett, S., Eichenberger, R.M., Nevagi, R.J., Ghaffar, K.A., Marasini, N., Dai, Y., Loukas, A., Toth, I., and Skwarczynski, M. (2019). Lipopeptide-based oral vaccine against hookworm infection. J. Infect. Dis.","DOI":"10.1093\/infdis\/jiz528"}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/8\/1\/23\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T14:05:03Z","timestamp":1760364303000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/8\/1\/23"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,13]]},"references-count":61,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,3]]}},"alternative-id":["vaccines8010023"],"URL":"https:\/\/doi.org\/10.3390\/vaccines8010023","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,13]]}}}