{"doi":"10.1172/jci152310","title":"Trivalent nucleoside-modified mRNA vaccine yields durable memory B cell protection against genital herpes in preclinical models","abstract":"Nucleoside-modified mRNA vaccines have gained global attention because of COVID-19. We evaluated a similar vaccine approach for preventing a chronic, latent genital infection rather than an acute respiratory infection. We used animal models to compare an HSV-2 trivalent nucleoside-modified mRNA vaccine with the same antigens prepared as proteins, with an emphasis on antigen-specific memory B cell responses and immune correlates of protection. In guinea pigs, serum neutralizing-antibody titers were higher at 1 month and declined far less by 8 months in mRNA- compared with protein-immunized animals. Both vaccines protected against death and genital lesions when infected 1 month after immunization; however, protection was more durable in the mRNA group compared with the protein group when infected after 8 months, an interval representing greater than 15% of the animal's lifespan. Serum and vaginal neutralizing-antibody titers correlated with protection against infection, as measured by genital lesions and vaginal virus titers 2 days after infection. In mice, the mRNA vaccine generated more antigen-specific memory B cells than the protein vaccine at early times after immunization that persisted for up to 1 year. High neutralizing titers and robust B cell immune memory likely explain the more durable protection by the HSV-2 mRNA vaccine.","journal":"Journal of Clinical Investigation","year":2021,"id":165937,"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":35,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9414,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":244594,"name":"James J. Knox","orcid":"0000-0002-3523-0661","position":1,"is_corresponding":false},{"id":475410,"name":"Angela Desmond","orcid":"0000-0002-8325-713X","position":2,"is_corresponding":false},{"id":231967,"name":"Mohamad‐Gabriel Alameh","orcid":"0000-0002-5672-6930","position":3,"is_corresponding":false},{"id":230381,"name":"Brian T. Gaudette","orcid":"0000-0001-6627-3085","position":4,"is_corresponding":false},{"id":691492,"name":"John M. Lubinski","orcid":null,"position":5,"is_corresponding":false},{"id":691493,"name":"Alexis Naughton","orcid":null,"position":6,"is_corresponding":false},{"id":412215,"name":"Lauren M. Hook","orcid":"0000-0002-5540-2459","position":7,"is_corresponding":false},{"id":412214,"name":"Kevin P. Egan","orcid":"0000-0002-6653-6110","position":8,"is_corresponding":false},{"id":54908,"name":"Ying K. Tam","orcid":"0000-0002-4083-5251","position":9,"is_corresponding":false},{"id":54904,"name":"Norbert Pardi","orcid":"0000-0003-1008-6242","position":10,"is_corresponding":false},{"id":230388,"name":"David Allman","orcid":"0000-0001-9345-1502","position":11,"is_corresponding":false},{"id":244597,"name":"Eline T. Luning Prak","orcid":"0000-0002-9478-9211","position":12,"is_corresponding":false},{"id":244598,"name":"Michael P. Cancro","orcid":"0000-0002-8659-3227","position":13,"is_corresponding":false},{"id":20753,"name":"Drew Weissman","orcid":"0000-0002-1501-6510","position":14,"is_corresponding":false},{"id":394965,"name":"Gary H. Cohen","orcid":"0000-0002-8581-8068","position":15,"is_corresponding":false},{"id":412216,"name":"Harvey M. Friedman","orcid":"0000-0002-0765-9460","position":16,"is_corresponding":false},{"id":412217,"name":"Sita Awasthi","orcid":"0000-0001-8230-3635","position":0,"is_corresponding":true}],"reference_count":52,"raw_metadata":null,"created_at":"2026-07-18T23:45:45.220559Z","pmid":"34618692","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":[]}