{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T10:59:32Z","timestamp":1763981972814,"version":"3.45.0"},"reference-count":38,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T00:00:00Z","timestamp":1763942400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Artgen Biotech PJSC"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Background: Antigen format strongly influences the immunogenicity of gene-based vaccines. Full-length Spike is widely used in licensed COVID-19 vaccines, while truncated subunits such as S1 or the receptor-binding domain (RBD) may simplify vector design but risk reduced potency. We aimed to compare these antigen formats in an AAV9 delivery platform. Methods: BALB\/c mice were immunized intramuscularly with recombinant AAV9 encoding full-length Spike, S1, or RBD at doses of 1 \u00d7 1010 or 1 \u00d7 1011 viral genomes. Immune responses were assessed by serology, virus neutralization, T-cell profiling, and histopathology. Results: All constructs expressed antigen in vitro and in vivo. Only full-length Spike elicited robust neutralizing antibodies at both doses, with titers rising significantly by week 12. High-dose RBD induced neutralization in a minority of animals, whereas S1 failed to do so. Antigen-specific IgG responses scaled with insert length (Spike &gt; S1 &gt; RBD). Cellular immunity was dominated by CD8+ effector memory T cells, strongest in the Spike group, which also induced measurable CD4+ responses. Local transient myositis was observed at the injection site but resolved by week 24, with no systemic pathology. Conclusions: Full-length Spike outperforms truncated subunits in the AAV context, highlighting antigen structure as a critical factor for next-generation coronavirus vaccine design.<\/jats:p>","DOI":"10.3390\/vaccines13121187","type":"journal-article","created":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T10:24:17Z","timestamp":1763979857000},"page":"1187","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Antigen Format Determines Immunogenicity of AAV-Based SARS-CoV-2 Vaccines: Full-Length Spike Versus Truncated Subunits"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7948-1254","authenticated-orcid":false,"given":"Anna V.","family":"Vakhrusheva","sequence":"first","affiliation":[{"name":"Betuvax JSC,  Moscow 119571, Russia"},{"name":"Swiftgen LLC, Moscow 119571, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria E.","family":"Frolova","sequence":"additional","affiliation":[{"name":"Swiftgen LLC, Moscow 119571, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5848-5117","authenticated-orcid":false,"given":"Arthur A.","family":"Isaev","sequence":"additional","affiliation":[{"name":"Artgen Biotech PJSC, Moscow 119571, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,24]]},"reference":[{"unstructured":"World Health Organization (2025, October 21). 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