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- Title
Human Cytomegalovirus mRNA-1647 Vaccine Candidate Elicits Potent and Broad Neutralization and Higher Antibody-Dependent Cellular Cytotoxicity Responses Than the gB/MF59 Vaccine.
- Authors
Hu, Xintao; Karthigeyan, Krithika P; Herbek, Savannah; Valencia, Sarah M; Jenks, Jennifer A; Webster, Helen; Miller, Itzayana G; Connors, Megan; Pollara, Justin; Andy, Caroline; Gerber, Linda M; Walter, Emmanuel B; Edwards, Kathryn M; Bernstein, David I; Hou, Jacob; Koch, Matthew; Panther, Lori; Carfi, Andrea; Wu, Kai; Permar, Sallie R
- 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).
- Subjects
ANTIBODY-dependent cell cytotoxicity; CLINICAL trial registries; ANTIBODY formation; IMMUNOGLOBULIN G; HUMAN cytomegalovirus
- Publication
Journal of Infectious Diseases, 2024, Vol 230, Issue 2, p455
- ISSN
0022-1899
- Publication type
Article
- DOI
10.1093/infdis/jiad593