{"doi":"10.1101/2023.08.02.23293386","title":"Human Cytomegalovirus mRNA-1647 Vaccine Candidate Elicits Potent and Broad Neutralization and Higher Antibody-Dependent Cellular Cytotoxicity Responses than that of the Partially Effective gB/MF59 Vaccine","abstract":"ABSTRACT Background The MF59-adjuvanted gB subunit (gB/MF59) vaccine demonstrated ~50% efficacy against human cytomegalovirus (HCMV) acquisition in multiple clinical trials, suggesting efforts to improve this vaccine design might yield a vaccine suitable for licensure. A vaccine candidate employing nucleoside-modified mRNAs encoding HCMV gB and pentameric complex (PC) encapsulated in lipid nanoparticle, mRNA-1647, is currently in late-stage efficacy trials. Yet, its immunogenicity has not been compared to the partially-effective gB/MF59 vaccine. Methods We assessed neutralizing and Fc-mediated IgG effector antibody responses induced by mRNA-1647, a vaccine comprising an equal mass of 6 mRNAs encoding gB and PC antigens, in both HCMV seropositive and seronegative vaccinees from a first-in-human clinical trial through 1-year following 3 rd vaccination using a systems serology approach. Further, we compared peak anti-gB antibody responses in seronegative mRNA-1647 vaccinees to that of seronegative female adolescent gB/MF59 vaccine recipients. Results mRNA-1647 vaccination boosted pre-existing HCMV-specific IgG responses in seropositive vaccinees, including neutralizing and Fc-mediated effector antibody responses. In seronegative vaccinees, mRNA-1647 induced durable and functional HCMV-specific IgG responses. Elicited gB-specific IgG responses were lower than the PC-specific IgG responses. Additionally, gB-specific IgG and antibody-dependent cellular phagocytosis (ADCP) responses were lower than those elicited by gB/MF59. However, mRNA-1647 elicited robust neutralization and high antibody-dependent cellular cytotoxicity (ADCC) responses. Conclusions mRNA-1647 vaccination induced polyfunctional and durable HCMV-specific antibody responses. mRNA-1647-elicited gB-specific IgG responses were lower than PC-specific IgG responses and lower than those elicited by the partially effective gB/MF59. However, higher neutralization and ADCC responses were elicited by mRNA-1647 than gB/MF59. Clinical Trials Registration ClinicalTrials.gov ( NCT03382405 , mRNA-1647) and ( NCT00133497 , gB/MF59). Summary mRNA-1647 HCMV vaccine elicited polyfunctional and durable antibody responses in humans. While the mRNA-1647-elicited glycoprotein B (gB)-specific IgG responses were lower than that of the moderately-effective gB/MF59 vaccine, the pentameric complex (PC)-specific IgG responses were strong.","journal":"medRxiv","year":2023,"id":390569,"datarank":0.3596842909197557,"base_score":2.3978952727983707,"endowment":2.3978952727983707,"self_citation_contribution":0.3596842909197557,"citation_network_contribution":0.0,"self_endowment_contribution":0.3596842909197557,"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":0.9557,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","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. Permar","orcid":"0000-0003-1438-4554","position":19,"is_corresponding":false},{"id":540989,"name":"Xintao Hu","orcid":"0000-0001-5633-3806","position":0,"is_corresponding":true}],"reference_count":34,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:18:37.743462Z","pmid":null,"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":[]}