{"doi":"10.1093/infdis/jiad593","title":"Human Cytomegalovirus mRNA-1647 Vaccine Candidate Elicits Potent and Broad Neutralization and Higher Antibody-Dependent Cellular Cytotoxicity Responses Than the gB/MF59 Vaccine","abstract":"BACKGROUND: MF59-adjuvanted gB subunit (gB/MF59) vaccine demonstrated approximately 50% efficacy against human cytomegalovirus (HCMV) acquisition in multiple clinical trials, suggesting that efforts to improve this vaccine design might yield a vaccine suitable for licensure. METHODS: A messenger RNA (mRNA)-based vaccine candidate encoding HCMV gB and pentameric complex (PC), mRNA-1647, is currently in late-stage efficacy trials. However, its immunogenicity has not been compared to the partially effective gB/MF59 vaccine. We assessed neutralizing and Fc-mediated immunoglobulin G (IgG) effector antibody responses induced by mRNA-1647 in both HCMV-seropositive and -seronegative vaccinees from a first-in-human clinical trial through 1 year following third vaccination using a systems serology approach. Furthermore, we compared peak anti-gB antibody responses in seronegative mRNA-1647 vaccinees to that of seronegative gB/MF59 vaccine recipients. RESULTS: mRNA-1647 vaccination elicited and boosted HCMV-specific IgG responses in seronegative and seropositive vaccinees, respectively, including neutralizing and Fc-mediated effector antibody responses. gB-specific IgG responses were lower than PC-specific IgG responses. gB-specific IgG and antibody-dependent cellular phagocytosis responses were lower than those elicited by gB/MF59. However, mRNA-1647 elicited higher neutralization and antibody-dependent cellular cytotoxicity (ADCC) responses. CONCLUSIONS: Overall, mRNA-1647 vaccination induced polyfunctional and durable HCMV-specific antibody responses, with lower gB-specific IgG responses but higher neutralization and ADCC responses compared to the gB/MF59 vaccine. CLINICAL TRIALS REGISTRATION: NCT03382405 (mRNA-1647) and NCT00133497 (gB/MF59).","journal":"The Journal of Infectious Diseases","year":2024,"id":417125,"datarank":1.543834282554139,"base_score":4.394449154672439,"endowment":4.394449154672439,"self_citation_contribution":0.6591673732008659,"citation_network_contribution":0.884666909353273,"self_endowment_contribution":0.6591673732008659,"citer_contribution":0.884666909353273,"corpus_percentile":null,"corpus_rank":null,"citation_count":80,"citer_count":75,"citers_with_citation_signal":53,"citers_with_endowment":53,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9632,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT03382405","NCT00133497"]},"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":738282,"name":"Krithika P. Karthigeyan","orcid":"0000-0002-1808-6688","position":1,"is_corresponding":false},{"id":811152,"name":"Savannah Herbek","orcid":"0000-0001-9394-3769","position":2,"is_corresponding":false},{"id":398380,"name":"Sarah Valencia","orcid":"0000-0002-8878-8407","position":3,"is_corresponding":false},{"id":344228,"name":"Jennifer A. Jenks","orcid":"0000-0002-6865-5615","position":4,"is_corresponding":false},{"id":398376,"name":"Helen Webster","orcid":"0000-0002-3046-7053","position":5,"is_corresponding":false},{"id":809974,"name":"Itzayana G. Miller","orcid":"0000-0001-9199-8985","position":6,"is_corresponding":false},{"id":1111507,"name":"M. Connors","orcid":"0000-0002-8588-1657","position":7,"is_corresponding":false},{"id":344231,"name":"Justin Pollara","orcid":"0000-0003-1892-4722","position":8,"is_corresponding":false},{"id":734546,"name":"Caroline Andy","orcid":null,"position":9,"is_corresponding":false},{"id":280501,"name":"Linda M. Gerber","orcid":"0000-0003-0081-3338","position":10,"is_corresponding":false},{"id":325734,"name":"Emmanuel B. Walter","orcid":"0000-0001-6502-6736","position":11,"is_corresponding":false},{"id":294609,"name":"Kathryn M. Edwards","orcid":"0000-0003-3912-9832","position":12,"is_corresponding":false},{"id":381556,"name":"David I. Bernstein","orcid":"0000-0002-0100-1991","position":13,"is_corresponding":false},{"id":1162848,"name":"Jacob Hou","orcid":null,"position":14,"is_corresponding":false},{"id":619697,"name":"Matthew Koch","orcid":null,"position":15,"is_corresponding":false},{"id":1162358,"name":"Lori Panther","orcid":"0000-0002-8223-9167","position":16,"is_corresponding":false},{"id":105615,"name":"Andrea Carfı́","orcid":"0000-0001-5508-3809","position":17,"is_corresponding":false},{"id":81062,"name":"Kaichun Wu","orcid":"0000-0002-0699-9666","position":18,"is_corresponding":false},{"id":240902,"name":"Sallie R. 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