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To address this challenge, we engineered and comprehensively tested three optimized mRNA vaccine candidates, evaluating the kinetics, quality, and magnitude of antibody responses as well as antigen-specific T cell immunity during a prime-boost vaccination regimen in mice. Among the tested candidates, TP2A encoding secreted receptor-binding domains (RBDs) derived from SARS-CoV-2 wild type (WT), Delta and Omicron variants demonstrated superior immunogenicity, inducing an early IgG2a-dominated antibody response against distinct SARS-CoV-2 spike (S) glycoprotein variants. In addition, TP2A elicited IFN-\u03b3-producing T cells in both spleen and draining lymph nodes and antigen-specific cytotoxic T lymphocytes. Notably, beyond broad immunity induced by the vaccine, TP2A functions as a modular platform, thus enabling flexible antigen assembly and rapid vaccine adaptation to newly emerging variants or even other viral pathogens. These findings position TP2A as a promising next-generation mRNA vaccine candidate.<\/jats:p>","DOI":"10.1038\/s41598-026-48481-8","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T10:13:15Z","timestamp":1780481595000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Rational design of a modular mRNA vaccine platform for rapid adaptation to SARS-CoV-2 variants"],"prefix":"10.1038","volume":"16","author":[{"given":"Julia","family":"Rudert","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Volckmar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Jeron","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maike","family":"B\u00e4lkner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pia","family":"Grimpe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henning","family":"Jacobsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dandan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovana Bavia","family":"Bampi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luka","family":"Cicin-Sain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dunja","family":"Bruder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Rosenecker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,3]]},"reference":[{"key":"48481_CR1","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1038\/s41541-025-01242-6","volume":"10","author":"J Pattyn","year":"2025","unstructured":"Pattyn, J. et al. 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