{"doi":"10.1038/s41541-024-00821-3","title":"Multivalent cytomegalovirus glycoprotein B nucleoside modified mRNA vaccines did not demonstrate a greater antibody breadth","abstract":"Human cytomegalovirus (HCMV) remains the most common congenital infection and infectious complication in immunocompromised patients. The most successful HCMV vaccine to date, an HCMV glycoprotein B (gB) subunit vaccine adjuvanted with MF59, achieved 50% efficacy against primary HCMV infection. A previous study demonstrated that gB/MF59 vaccinees were less frequently infected with HCMV gB genotype strains most similar to the vaccine strain than strains encoding genetically distinct gB genotypes, suggesting strain-specific immunity accounted for the limited efficacy. To determine whether vaccination with multiple HCMV gB genotypes could increase the breadth of anti-HCMV gB humoral and cellular responses, we immunized 18 female rabbits with monovalent (gB-1), bivalent (gB-1+gB-3), or pentavalent (gB-1+gB-2+gB-3+gB-4+gB-5) gB lipid nanoparticle-encapsulated nucleoside-modified RNA (mRNA-LNP) vaccines. The multivalent vaccine groups did not demonstrate a higher magnitude or breadth of the IgG response to the gB ectodomain or cell-associated gB compared to that of the monovalent vaccine. Also, the multivalent vaccines did not show an increase in the breadth of neutralization activity and antibody-dependent cellular phagocytosis against HCMV strains encoding distinct gB genotypes. Interestingly, peripheral blood mononuclear cell-derived gB-2-specific T-cell responses elicited by multivalent vaccines were of a higher magnitude compared to that of monovalent vaccinated animals against a vaccine-mismatched gB genotype at peak immunogenicity. Yet, no statistical differences were observed in T cell response against gB-3 and gB-5 variable regions among the three vaccine groups. Our data suggests that the inclusion of multivalent gB antigens is not an effective strategy to increase the breadth of anti-HCMV gB antibody and T cell responses. Understanding how to increase the HCMV vaccine protection breadth will be essential to improve the vaccine efficacy.","journal":"npj Vaccines","year":2024,"id":431987,"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":15,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.959,"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":644231,"name":"Leike Li","orcid":"0000-0002-1379-1396","position":1,"is_corresponding":false},{"id":344227,"name":"Cody S. Nelson","orcid":"0000-0002-1046-455X","position":2,"is_corresponding":false},{"id":286037,"name":"Richard Barfield","orcid":"0000-0002-6276-7704","position":3,"is_corresponding":false},{"id":398380,"name":"Sarah Valencia","orcid":"0000-0002-8878-8407","position":4,"is_corresponding":false},{"id":432169,"name":"Cliburn Chan","orcid":"0000-0001-5901-6806","position":5,"is_corresponding":false},{"id":20749,"name":"Hiromi Muramatsu","orcid":"0000-0003-1544-1493","position":6,"is_corresponding":false},{"id":234005,"name":"Paulo J.C. Lin","orcid":null,"position":7,"is_corresponding":false},{"id":54904,"name":"Norbert Pardi","orcid":"0000-0003-1008-6242","position":8,"is_corresponding":false},{"id":105313,"name":"Zhiqiang An","orcid":"0000-0001-9309-2335","position":9,"is_corresponding":false},{"id":20753,"name":"Drew Weissman","orcid":"0000-0002-1501-6510","position":10,"is_corresponding":false},{"id":240902,"name":"Sallie R. Permar","orcid":"0000-0003-1438-4554","position":11,"is_corresponding":false},{"id":398377,"name":"Hsuan-Yuan Wang","orcid":"0000-0001-9248-4281","position":0,"is_corresponding":true}],"reference_count":73,"raw_metadata":null,"created_at":"2026-07-19T01:59:30.747263Z","pmid":"38378950","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":[]}