{"doi":"10.1038/s41541-024-00957-2","title":"Broad protection and respiratory immunity of dual mRNA vaccination against SARS-CoV-2 variants","abstract":"While first-generation, spike (S)-based COVID-19 vaccines were effective against early SARS-CoV-2 strains, the rapid evolution of novel Omicron subvariants have substantially reduced vaccine efficacy. As such, broadly protective vaccines against SARS-CoV-2 are needed to prevent future viral emergence. In addition, it remains less clear whether peripheral immunization, especially with mRNA vaccines, elicits effective respiratory immunity. Our group has developed a nucleoside-modified mRNA vaccine expressing the nucleocapsid (N) protein of the ancestral SARS-CoV-2 virus and has tested its use in combination with the S-based mRNA vaccine (mRNA-S). In this study, we examined efficacy of mRNA-N alone or in combination with mRNA-S (mRNA-S+N) against more immune evasive Omicron variants in hamsters. Our data show that mRNA-N alone induces a modest but significant protection against BA.5 and that dual mRNA-S+N vaccination confers complete protection against both BA.5 and BQ.1, preventing detection of virus in the hamster lungs. Analysis of respiratory immune response in mice shows that intramuscular mRNA-S+N immunization effectively induces respiratory S- and N-specific T cell responses in the lungs and in bronchoalveolar lavage (BAL), as well as antigen-specific binding IgG in BAL. Together, our data further support mRNA-S+N as a potential pan-COVID-19 vaccine for broad protection against current and emerging SARS-CoV-2 variants.","journal":"npj Vaccines","year":2024,"id":438986,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9483,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":105300,"name":"Jessica A. Plante","orcid":"0000-0002-4768-7458","position":1,"is_corresponding":false},{"id":94979,"name":"Srinivasa Reddy Bonam","orcid":"0000-0002-2888-2418","position":2,"is_corresponding":false},{"id":555186,"name":"Grace Rafael","orcid":null,"position":3,"is_corresponding":false},{"id":426950,"name":"Yuejin Liang","orcid":"0000-0002-9557-1847","position":4,"is_corresponding":false},{"id":819440,"name":"Nicholas C. Hazell","orcid":null,"position":5,"is_corresponding":false},{"id":923101,"name":"Jordyn Walker","orcid":null,"position":6,"is_corresponding":false},{"id":910269,"name":"Rachel A. Reyna","orcid":"0000-0001-8421-8397","position":7,"is_corresponding":false},{"id":439576,"name":"David H. Walker","orcid":"0000-0002-3309-4360","position":8,"is_corresponding":false},{"id":231967,"name":"Mohamad‐Gabriel Alameh","orcid":"0000-0002-5672-6930","position":9,"is_corresponding":false},{"id":20753,"name":"Drew Weissman","orcid":"0000-0002-1501-6510","position":10,"is_corresponding":false},{"id":105319,"name":"Scott C. Weaver","orcid":"0000-0001-8016-8556","position":11,"is_corresponding":false},{"id":105318,"name":"Kenneth S. Plante","orcid":"0000-0002-7485-3167","position":12,"is_corresponding":false},{"id":426956,"name":"Haitao Hu","orcid":"0000-0002-6964-2314","position":13,"is_corresponding":false},{"id":699239,"name":"Renee L. Hajnik","orcid":"0000-0002-6492-518X","position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":null,"created_at":"2026-07-19T02:00:47.992543Z","pmid":"39232020","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}