中和
病毒学
免疫原性
抗体依赖性细胞介导的细胞毒性
抗体
人巨细胞病毒
接种疫苗
免疫学
免疫系统
生物
医学
病毒
单克隆抗体
作者
Xintao Hu,Krithika P Karthigeyan,Savannah Herbek,Sarah Valencia,Jennifer A. Jenks,Helen Webster,Itzayana G Miller,M. Connors,Justin Pollara,Caroline Andy,Linda M. Gerber,Emmanuel B. Walter,Kathryn M. Edwards,David I. Bernstein,Jun Hou,Matthew A. Koch,Lori Panther,Andrea Carfı́,Kai Wu,Sallie R. Permar
标识
DOI:10.1093/infdis/jiad593
摘要
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).
科研通智能强力驱动
Strongly Powered by AbleSci AI