{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T01:35:11Z","timestamp":1788572111839,"version":"build-2803163510"},"reference-count":94,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T00:00:00Z","timestamp":1770940800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"National Science Centre","doi-asserted-by":"publisher","award":["2019\/35\/B\/NZ6\/04002"],"award-info":[{"award-number":["2019\/35\/B\/NZ6\/04002"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>The development of a universal SARS-CoV-2 vaccine holds great promise for achieving broad and durable protection against existing and future coronavirus variants. The identification, selection, and rational redesign of conserved viral epitopes constitute the direct immunological foundation of universal SARS-CoV-2 vaccine development. The breadth and durability of protection are therefore primarily determined at the level of antigen and epitope design, whereas adjuvants, delivery platforms, and routes of administration serve as enabling and amplifying components rather than primary drivers of universality. Accordingly, this review discusses key determinants of universal vaccine design, including antigen selection, adjuvant utilization, and route of administration. The spike protein, particularly its receptor-binding domain, is a major antigenic target, but its high mutation rate challenges long-term vaccine efficacy. Strategies focusing on conserved epitopes in antigen designs show potential to elicit cross-neutralizing immune responses. Nanoparticle-based vaccines capable of presenting multiple homologous or heterologous antigens have demonstrated enhanced immunogenicity, broad protection in preclinical models and safety in clinical trials. The addition of next-generation adjuvants further amplifies humoral and cellular immunity beyond the capabilities of traditional aluminum-based adjuvants. Moreover, mucosal vaccine delivery may provide superior local protection at viral entry sites and limit transmission. Importantly, integrating these technological advances with epitope-centered antigen design and immunological data from vaccinated individuals will accelerate the identification of conserved epitopes and inform future vaccine design. A multidisciplinary approach combining optimized antigen engineering, novel adjuvant systems, and innovative delivery strategies is essential for the realization of a broadly protective universal SARS-CoV-2 vaccine.<\/jats:p>","DOI":"10.3390\/vaccines14020173","type":"journal-article","created":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T09:09:19Z","timestamp":1770973759000},"page":"173","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Challenges and Prospects in the Development of a Universal SARS-CoV-2 Vaccine"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2679-3112","authenticated-orcid":false,"given":"Kacper","family":"Karczmarzyk","sequence":"first","affiliation":[{"name":"Department of Biomedical Research, National Medicines Institute, Che\u0142mska 30\/34, 00-725 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1363-7986","authenticated-orcid":false,"given":"Ma\u0142gorzata","family":"K\u0119sik-Brodacka","sequence":"additional","affiliation":[{"name":"Department of Biomedical Research, National Medicines Institute, Che\u0142mska 30\/34, 00-725 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,13]]},"reference":[{"key":"ref_1","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":"2020","journal-title":"Nat. Rev. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"D7","DOI":"10.1016\/j.vaccine.2011.06.080","article-title":"The eradication of smallpox\u2014An overview of the past, present, and future","volume":"29","author":"Henderson","year":"2011","journal-title":"Vaccine"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1038\/nri3694","article-title":"From empiricism to rational design: A personal perspective of the evolution of vaccine development","volume":"14","author":"Rappuoli","year":"2014","journal-title":"Nat. Rev. Immunol."},{"key":"ref_4","first-page":"17","article-title":"The Genome Revolution in Vaccine Research","volume":"6","author":"Capecchi","year":"2004","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1111\/cei.13295","article-title":"Emerging viruses and current strategies for vaccine intervention","volume":"196","author":"Afrough","year":"2019","journal-title":"Clin. Exp. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1002\/jmv.25593","article-title":"Why are vaccines against many human viral diseases still unavailable; an historic perspective?","volume":"92","author":"Tannock","year":"2019","journal-title":"J. Med. Virol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1038\/s41541-022-00597-4","article-title":"Challenges and developments in universal vaccine design against SARS-CoV-2 variants","volume":"7","author":"Zhao","year":"2022","journal-title":"npj Vaccines"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1038\/s41591-021-01413-7","article-title":"Evidence for increased breakthrough rates of SARS-CoV-2 variants of concern in BNT162b2-mRNA-vaccinated individuals","volume":"27","author":"Kustin","year":"2021","journal-title":"Nat. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2331","DOI":"10.1016\/S0140-6736(21)01290-3","article-title":"Neutralising antibody activity against SARS-CoV-2 VOCs B.1.617.2 and B.1.351 by BNT162b2 vaccination","volume":"397","author":"Wall","year":"2021","journal-title":"Lancet"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1056\/NEJMc2206576","article-title":"Neutralization Escape by SARS-CoV-2 Omicron Subvariants BA.2.12.1, BA.4, and BA.5","volume":"387","author":"Hachmann","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.1056\/NEJMc2201849","article-title":"Neutralization of the SARS-CoV-2 Omicron BA.1 and BA.2 Variants","volume":"386","author":"Yu","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1586\/erv.10.123","article-title":"Cross-protective immunity to influenza A viruses","volume":"9","author":"Epstein","year":"2010","journal-title":"Expert Rev. Vaccines"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1038\/s41423-023-01116-8","article-title":"In search of a pan-coronavirus vaccine: Next-generation vaccine design and immune mechanisms","volume":"21","author":"Cankat","year":"2023","journal-title":"Cell. Mol. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1056\/NEJMp2118468","article-title":"Universal Coronavirus Vaccines\u2014An Urgent Need","volume":"386","author":"Morens","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Dangi, T., Palacio, N., Sanchez, S., Park, M., Class, J., Visvabharathy, L., Ciucci, T., Koralnik, I.J., Richner, J.M., and Penaloza-MacMaster, P. (2021). Cross-protective immunity following coronavirus vaccination and coronavirus infection. J. Clin. Investig., 131.","DOI":"10.1172\/JCI151969"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Wang, C.Y., Hwang, K.-P., Kuo, H.-K., Peng, W.-J., Shen, Y.-H., Kuo, B.-S., Huang, J.-H., Liu, H., Ho, Y.-H., and Lin, F. (2022). A multitope SARS-CoV-2 vaccine provides long-lasting B cell and T cell immunity against Delta and Omicron variants. J. Clin. Investig., 132.","DOI":"10.1172\/JCI157707"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"13922","DOI":"10.1038\/s41598-022-18279-5","article-title":"Infections with the SARS-CoV-2 Delta variant exhibit fourfold increased viral loads in the upper airways compared to Alpha or non-variants of concern","volume":"12","author":"Dingemans","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.1056\/NEJMoa2110345","article-title":"Safety and Efficacy of the BNT162b2 mRNA COVID-19 Vaccine through 6 Months","volume":"385","author":"Thomas","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"msac091","DOI":"10.1093\/molbev\/msac091","article-title":"Genetic and Structural Analysis of SARS-CoV-2 Spike Protein for Universal Epitope Selection","volume":"39","author":"Markosian","year":"2022","journal-title":"Mol. Biol. Evol."},{"key":"ref_20","first-page":"523","article-title":"A universal flu vaccine","volume":"61","author":"Plucienniczak","year":"2014","journal-title":"Acta Biochim. Pol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e2123477119","DOI":"10.1073\/pnas.2123477119","article-title":"Researchers getting closer to a \u201cuniversal\u201d flu vaccine","volume":"119","author":"Beans","year":"2022","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"102369","DOI":"10.1016\/j.eclinm.2023.102369","article-title":"The potential epidemiologic, clinical, and economic value of a universal coronavirus vaccine: A modelling study","volume":"68","author":"Bartsch","year":"2024","journal-title":"eClinicalMedicine"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1038\/s41586-020-2739-1","article-title":"The coding capacity of SARS-CoV-2","volume":"589","author":"Finkel","year":"2020","journal-title":"Nature"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1038\/s41586-020-2852-1","article-title":"SARS-CoV-2 neutralizing antibody structures inform therapeutic strategies","volume":"588","author":"Barnes","year":"2020","journal-title":"Nature"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.bbrc.2014.07.090","article-title":"Antibody-dependent SARS coronavirus infection is mediated by antibodies against spike proteins","volume":"451","author":"Wang","year":"2014","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e02015","DOI":"10.1128\/JVI.02015-19","article-title":"Molecular Mechanism for Antibody-Dependent Enhancement of Coronavirus Entry","volume":"94","author":"Wan","year":"2020","journal-title":"J. Virol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"5853","DOI":"10.1021\/acs.jcim.0c00501","article-title":"Decoding SARS-CoV-2 Transmission and Evolution and Ramifications for COVID-19 Diagnosis, Vaccine, and Medicine","volume":"60","author":"Wang","year":"2020","journal-title":"J. Chem. Inf. Model."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Guo, Y., He, W., Mou, H., Zhang, L., Chang, J., Peng, S., Ojha, A., Tavora, R., Parcells, M.S., and Luo, G. (2021). An Engineered Receptor-Binding Domain Improves the Immunogenicity of Multivalent SARS-CoV-2 Vaccines. mBio, 12.","DOI":"10.1128\/mBio.00930-21"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1038\/s41392-021-00750-w","article-title":"The self-assembled nanoparticle-based trimeric RBD mRNA vaccine elicits robust and durable protective immunity against SARS-CoV-2 in mice","volume":"6","author":"Sun","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1038\/s41586-022-04980-y","article-title":"BA.2.12.1, BA.4 and BA.5 escape antibodies elicited by Omicron infection","volume":"608","author":"Cao","year":"2022","journal-title":"Nature"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1038\/s41586-022-04594-4","article-title":"Antibody evasion properties of SARS-CoV-2 Omicron sublineages","volume":"604","author":"Iketani","year":"2022","journal-title":"Nature"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1016\/j.immuni.2023.02.005","article-title":"Broadly neutralizing anti-S2 antibodies protect against all three human betacoronaviruses that cause deadly disease","volume":"56","author":"Zhou","year":"2023","journal-title":"Immunity"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1038\/s41591-018-0042-6","article-title":"Epitope-based vaccine design yields fusion peptide-directed antibodies that neutralize diverse strains of HIV-1","volume":"24","author":"Xu","year":"2018","journal-title":"Nat. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1038\/s41591-020-1118-7","article-title":"A chimeric hemagglutinin-based universal influenza virus vaccine approach induces broad and long-lasting immunity in a randomized, placebo-controlled phase I trial","volume":"27","author":"Nachbagauer","year":"2020","journal-title":"Nat. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1038\/s41392-023-01472-x","article-title":"Targetable elements in SARS-CoV-2 S2 subunit for the design of pan-coronavirus fusion inhibitors and vaccines","volume":"8","author":"Guo","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"eabn3715","DOI":"10.1126\/scitranslmed.abn3715","article-title":"SARS-CoV-2 S2\u2013targeted vaccination elicits broadly neutralizing antibodies","volume":"14","author":"Ng","year":"2022","journal-title":"Sci. Transl. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"104341","DOI":"10.1016\/j.ebiom.2022.104341","article-title":"Multivalent S2-based vaccines provide broad protection against SARS-CoV-2 variants of concern and pangolin coronaviruses","volume":"86","author":"Halfmann","year":"2022","journal-title":"eBioMedicine"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1111\/imm.13443","article-title":"New-onset autoimmune phenomena post-COVID-19 vaccination","volume":"165","author":"Chen","year":"2022","journal-title":"Immunology"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Gracia-Ramos, A.E., Martin-Nares, E., and Hern\u00e1ndez-Molina, G. (2021). New Onset of Autoimmune Diseases Following COVID-19 Diagnosis. Cells, 10.","DOI":"10.3390\/cells10123592"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2991","DOI":"10.3390\/v6082991","article-title":"The Coronavirus Nucleocapsid Is a Multifunctional Protein","volume":"6","author":"McBride","year":"2014","journal-title":"Viruses"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.1126\/science.1085953","article-title":"The Genome Sequence of the SARS-Associated Coronavirus","volume":"300","author":"Marra","year":"2003","journal-title":"Science"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/j.chom.2020.03.002","article-title":"A Sequence Homology and Bioinformatic Approach Can Predict Candidate Targets for Immune Responses to SARS-CoV-2","volume":"27","author":"Grifoni","year":"2020","journal-title":"Cell Host Microbe"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Cong, Y., Ulasli, M., Schepers, H., Mauthe, M., V\u2019Kovski, P., Kriegenburg, F., Thiel, V., de Haan, C.A.M., and Reggiori, F. (2020). Nucleocapsid Protein Recruitment to Replication-Transcription Complexes Plays a Crucial Role in Coronaviral Life Cycle. J. Virol., 94.","DOI":"10.1128\/JVI.01925-19"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Hensen, L., Illing, P.T., Rowntree, L.C., Davies, J., Miller, A., Tong, S.Y.C., Habel, J.R., van de Sandt, C.E., Flanagan, K.L., and Purcell, A.W. (2022). T Cell Epitope Discovery in the Context of Distinct and Unique Indigenous HLA Profiles. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.812393"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1038\/s41423-022-00838-5","article-title":"T cell epitopes in SARS-CoV-2 proteins are substantially conserved in the Omicron variant","volume":"19","author":"Choi","year":"2022","journal-title":"Cell. Mol. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"111995","DOI":"10.1016\/j.celrep.2023.111995","article-title":"Prevalent and immunodominant CD8 T cell epitopes are conserved in SARS-CoV-2 variants","volume":"42","author":"Meyer","year":"2023","journal-title":"Cell Rep."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Wang, C.Y., Peng, W.-J., Kuo, B.-S., Ho, Y.-H., Wang, M.-S., Yang, Y.-T., Chang, P.-Y., Shen, Y.-H., and Hwang, K.-P. (2023). Toward a pan-SARS-CoV-2 vaccine targeting conserved epitopes on spike and non-spike proteins for potent, broad and durable immune responses. PLOS Pathog., 19.","DOI":"10.1371\/journal.ppat.1010870"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Prakash, S., Dhanushkodi, N.R., Zayou, L., Ibraim, I.C., Quadiri, A., Coulon, P.G., Tifrea, D.F., Suzer, B., Shaik, A.M., and Chilukuri, A. (2024). Cross-protection induced by highly conserved human B, CD4+, and CD8+ T-cell epitopes-based vaccine against severe infection, disease, and death caused by multiple SARS-CoV-2 variants of concern. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1328905"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"16731","DOI":"10.1038\/s41598-022-21207-2","article-title":"A novel vaccine based on SARS-CoV-2 CD4+ and CD8+ T cell conserved epitopes from variants Alpha to Omicron","volume":"12","author":"Wallace","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1016\/j.cell.2021.01.007","article-title":"Adaptive immunity to SARS-CoV-2 and COVID-19","volume":"184","author":"Sette","year":"2021","journal-title":"Cell"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.csbj.2015.11.001","article-title":"Self-assembling protein nanoparticles in the design of vaccines","volume":"14","author":"Malito","year":"2016","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/j.vaccine.2013.11.069","article-title":"Nanoparticle vaccines","volume":"32","author":"Zhao","year":"2014","journal-title":"Vaccine"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1080\/14760584.2019.1578216","article-title":"Immunological basis for enhanced immunity of nanoparticle vaccines","volume":"18","author":"Kelly","year":"2019","journal-title":"Expert Rev. Vaccines"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1126\/science.abf6840","article-title":"Mosaic nanoparticles elicit cross-reactive immune responses to zoonotic coronaviruses in mice","volume":"371","author":"Cohen","year":"2021","journal-title":"Science"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"103699","DOI":"10.1016\/j.ebiom.2021.103699","article-title":"Current and future nanoparticle vaccines for COVID-19","volume":"74","author":"Vu","year":"2021","journal-title":"EBioMedicine"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e2301034","DOI":"10.1002\/advs.202301034","article-title":"A Mosaic Nanoparticle Vaccine Elicits Potent Mucosal Immune Response with Significant Cross-Protection Activity against Multiple SARS-CoV-2 Sublineages","volume":"10","author":"Zhang","year":"2023","journal-title":"Adv. Sci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"4291","DOI":"10.1016\/j.apsb.2023.01.010","article-title":"A novel heterologous receptor-binding domain dodecamer universal mRNA vaccine against SARS-CoV-2 variants","volume":"13","author":"Qin","year":"2023","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Qin, J., Jeon, J.H., Xu, J., Langston, L.K., Marasini, R., Mou, S., Montoya, B., Melo-Silva, C.R., Jeon, H.J., and Zhu, T. (2023). Design and preclinical evaluation of a universal SARS-CoV-2 mRNA vaccine. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1126392"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"5554","DOI":"10.1016\/j.cell.2024.07.052","article-title":"Mosaic sarbecovirus nanoparticles elicit cross-reactive responses in pre-vaccinated animals","volume":"187","author":"Cohen","year":"2024","journal-title":"Cell"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"110624","DOI":"10.1016\/j.isci.2024.110624","article-title":"SARS-CoV-2 ferritin nanoparticle vaccines produce hyperimmune equine sera with broad sarbecovirus activity","volume":"27","author":"Martinez","year":"2024","journal-title":"iScience"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2149","DOI":"10.1038\/s41467-023-37417-9","article-title":"A ferritin-based COVID-19 nanoparticle vaccine that elicits robust, durable, broad-spectrum neutralizing antisera in non-human primates","volume":"14","author":"Weidenbacher","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"110143","DOI":"10.1016\/j.celrep.2021.110143","article-title":"SARS-CoV-2 ferritin nanoparticle vaccines elicit broad SARS coronavirus immunogenicity","volume":"37","author":"Joyce","year":"2021","journal-title":"Cell Rep."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"eabi5735","DOI":"10.1126\/scitranslmed.abi5735","article-title":"A SARS-CoV-2 ferritin nanoparticle vaccine elicits protective immune responses in nonhuman primates","volume":"14","author":"Joyce","year":"2022","journal-title":"Sci. Transl. Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"e581","DOI":"10.1016\/S2666-5247(23)00410-X","article-title":"SARS-CoV-2 recombinant spike ferritin nanoparticle vaccine adjuvanted with Army Liposome Formulation containing monophosphoryl lipid A and QS-21: A phase 1, randomised, double-blind, placebo-controlled, first-in-human clinical trial","volume":"5","author":"Shepherd","year":"2024","journal-title":"Lancet Microbe"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1080\/14760584.2023.2211153","article-title":"Advances in SARS-CoV-2 receptor-binding domain-based COVID-19 vaccines","volume":"22","author":"Guan","year":"2023","journal-title":"Expert Rev. Vaccines"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1038\/s41541-024-00922-z","article-title":"Universal subunit vaccine protects against multiple SARS-CoV-2 variants and SARS-CoV","volume":"9","author":"Wang","year":"2024","journal-title":"npj Vaccines"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"e15821","DOI":"10.15252\/emmm.202215821","article-title":"A universal SARS-CoV DNA vaccine inducing highly cross-reactive neutralizing antibodies and T cells","volume":"14","author":"Appelberg","year":"2022","journal-title":"EMBO Mol. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2265","DOI":"10.1016\/j.cell.2022.04.029","article-title":"Protective prototype-Beta and Delta-Omicron chimeric RBD-dimer vaccines against SARS-CoV-2","volume":"185","author":"Xu","year":"2022","journal-title":"Cell"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Kang, X., Liu, S., Han, P., Lei, W., Xu, K., Xu, Z., Gao, Z., Zhou, X., and An, Y. (2023). Broad protective RBD heterotrimer vaccines neutralize SARS-CoV-2 including Omicron sub-variants XBB\/BQ.1.1\/BF.7. PLOS Pathog., 19.","DOI":"10.1371\/journal.ppat.1011659"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1038\/s41422-022-00720-z","article-title":"mRNA vaccines expressing homo-prototype\/Omicron and hetero-chimeric RBD-dimers against SARS-CoV-2","volume":"32","author":"Han","year":"2022","journal-title":"Cell Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"109719","DOI":"10.1016\/j.isci.2024.109719","article-title":"A spike virosome vaccine induces pan-sarbecovirus antibody responses in mice","volume":"27","author":"Brinkkemper","year":"2024","journal-title":"iScience"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Verma, S.K., Mahajan, P., Singh, N.K., Gupta, A., Aggarwal, R., Rappuoli, R., and Johri, A.K. (2023). New-age vaccine adjuvants, their development, and future perspective. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1043109"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.fmre.2021.01.010","article-title":"Immunoengineered adjuvants for universal vaccines against respiratory viruses","volume":"1","author":"Wang","year":"2021","journal-title":"Fundam. Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"51","DOI":"10.4110\/in.2015.15.2.51","article-title":"Recent Advances of Vaccine Adjuvants for Infectious Diseases","volume":"15","author":"Lee","year":"2015","journal-title":"Immune Netw."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.it.2008.09.006","article-title":"New horizons in adjuvants for vaccine development","volume":"30","author":"Reed","year":"2009","journal-title":"Trends Immunol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/S0169-409X(98)00008-8","article-title":"Aluminum compounds as vaccine adjuvants","volume":"32","author":"Gupta","year":"1998","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_77","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_78","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1038\/s41392-023-01371-1","article-title":"Universal selenium nanoadjuvant with immunopotentiating and redox-shaping activities inducing high-quality immunity for SARS-CoV-2 vaccine","volume":"8","author":"Lai","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_79","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_80","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1111\/j.1365-3083.2009.02319.x","article-title":"Mucosal Immunity: Induction, Dissemination, and Effector Functions","volume":"70","author":"Brandtzaeg","year":"2009","journal-title":"Scand. J. Immunol."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Karczmarzyk, K., and K\u0119sik-Brodacka, M. (2022). Attacking the Intruder at the Gate: Prospects of Mucosal Anti SARS-CoV-2 Vaccines. Pathogens, 11.","DOI":"10.3390\/pathogens11020117"},{"key":"ref_82","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":"2021","journal-title":"Nat. Rev. Immunol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1038\/s41385-022-00511-0","article-title":"Systemic and mucosal IgA responses are variably induced in response to SARS-CoV-2 mRNA vaccination and are associated with protection against subsequent infection","volume":"15","author":"Isho","year":"2022","journal-title":"Mucosal Immunol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"eabl9105","DOI":"10.1126\/sciimmunol.abl9105","article-title":"SARS-CoV-2 infection generates tissue-localized immunological memory in humans","volume":"6","author":"Poon","year":"2021","journal-title":"Sci. Immunol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"3010","DOI":"10.1038\/s41467-021-23333-3","article-title":"Peripheral and lung resident memory T cell responses against SARS-CoV-2","volume":"12","author":"Massana","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"eadd4853","DOI":"10.1126\/sciimmunol.add4853","article-title":"Respiratory mucosal immunity against SARS-CoV-2 after mRNA vaccination","volume":"7","author":"Tang","year":"2022","journal-title":"Sci. Immunol."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Ren, C., Gao, Y., Zhang, C., Zhou, C., Hong, Y., Qu, M., Zhao, Z., Du, Y., Yang, L., and Liu, B. (2022). Respiratory Mucosal Immunity: Kinetics of Secretory Immunoglobulin A in Sputum and Throat Swabs From COVID-19 Patients and Vaccine Recipients. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.782421"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1056\/NEJMoa2203965","article-title":"Effects of Previous Infection and Vaccination on Symptomatic Omicron Infections","volume":"387","author":"Altarawneh","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1016\/S0140-6736(22)02465-5","article-title":"Past SARS-CoV-2 infection protection against re-infection: A systematic review and meta-analysis","volume":"401","author":"Stein","year":"2023","journal-title":"Lancet"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1038\/s41591-022-01816-0","article-title":"Infectious viral load in unvaccinated and vaccinated individuals infected with ancestral, Delta or Omicron SARS-CoV-2","volume":"28","author":"Puhach","year":"2022","journal-title":"Nat. Med."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"6762","DOI":"10.1038\/s41467-023-42349-5","article-title":"An interferon-integrated mucosal vaccine provides pan-sarbecovirus protection in small animal models","volume":"14","author":"Yuen","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Hyun, H., Nham, E., Seong, H., Yoon, J.G., Noh, J.Y., Cheong, H.J., Kim, W.J., Yoon, S.K., Park, S.-J., and Gwak, W. (2024). Long-term humoral and cellular immunity against vaccine strains and Omicron subvariants (BQ.1.1, BN.1, XBB.1, and EG.5) after bivalent COVID-19 vaccination. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1385135"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1038\/s41421-024-00648-1","article-title":"Potent and broadly neutralizing antibodies against sarbecoviruses induced by sequential COVID-19 vaccination","volume":"10","author":"Zhao","year":"2024","journal-title":"Cell Discov."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"4748","DOI":"10.1038\/s41467-025-60024-9","article-title":"Comparative duration of neutralizing responses and protections of COVID-19 vaccination and correlates of protection","volume":"16","author":"Liu","year":"2025","journal-title":"Nat. Commun."}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/14\/2\/173\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T09:28:55Z","timestamp":1770974935000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/14\/2\/173"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,13]]},"references-count":94,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["vaccines14020173"],"URL":"https:\/\/doi.org\/10.3390\/vaccines14020173","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,13]]}}}