{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Abt ER"],"funding":["HHS | NIH | National Cancer Institute","NCI NIH HHS","HHS | NIH | National Cancer Institute (NCI)","California HIV/AIDS Research Program","California HIV/AIDS Research Program (CHRP)"],"pagination":["e2406332121"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11626164"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["121(49)"],"pubmed_abstract":["Combining a T cell-targeting mRNA vaccine encoding the conserved SARS-CoV-2 RNA-dependent RNA polymerase, RdRp, with a Spike-encoding mRNA vaccine may offer an additional pathway toward COVID-19 protection. Here, we show that a nucleoside-modified RdRp mRNA vaccine raises robust and durable CD8+ T cell responses in mice. Immunization drives a CD8+ T cell response enriched toward a specific RdRp epitope. Unexpectedly, coadministration of mRNA vaccines encoding RdRp or the Spike Receptor Binding Domain (RBD) dampens RBD-specific immune responses. Contralateral administration reduces the suppression of RBD-specific T cell responses while type I interferon signaling blockade restores RBD-specific antibodies. A staggered immunization strategy maintains both RBD vaccine-mediated antibody and T c"],"journal":["Proceedings of the National Academy of Sciences of the United States of America"],"pubmed_title":["Staggered immunization with mRNA vaccines encoding SARS-CoV-2 polymerase or spike antigens broadens the T cell epitope repertoire."],"pmcid":["PMC11626164"],"funding_grant_id":["H22BD4466","R01 CA250529","1R01CA250529-01A1","T32 CA009120"],"pubmed_authors":["Cheng D","Arumugaswami V","Jeyachandran AV","Burton Sojo G","Tran W","Lam AK","Noguchi M","Comai L","Rashid K","Teng PL","McLaughlin J","Tam YK","Nesterenko PA","Creech AL","Henley JE","Pardi N","Witte ON","Wu TT","Abt ER","Mao Z","Radu CG"],"additional_accession":[]},"is_claimable":false,"name":"Staggered immunization with mRNA vaccines encoding SARS-CoV-2 polymerase or spike antigens broadens the T cell epitope repertoire.","description":"Combining a T cell-targeting mRNA vaccine encoding the conserved SARS-CoV-2 RNA-dependent RNA polymerase, RdRp, with a Spike-encoding mRNA vaccine may offer an additional pathway toward COVID-19 protection. Here, we show that a nucleoside-modified RdRp mRNA vaccine raises robust and durable CD8+ T cell responses in mice. Immunization drives a CD8+ T cell response enriched toward a specific RdRp epitope. Unexpectedly, coadministration of mRNA vaccines encoding RdRp or the Spike Receptor Binding Domain (RBD) dampens RBD-specific immune responses. Contralateral administration reduces the suppression of RBD-specific T cell responses while type I interferon signaling blockade restores RBD-specific antibodies. A staggered immunization strategy maintains both RBD vaccine-mediated antibody and T c","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Dec","modification":"2026-06-02T04:38:14.244Z","creation":"2025-04-19T14:36:30.213Z"},"accession":"S-EPMC11626164","cross_references":{"pubmed":["39589869"],"doi":["10.1073/pnas.2406332121"]}}