A conditionally replication-defective cytomegalovirus vaccine elicits potent and diverse functional monoclonal antibodies in a phase I clinical trial

• Published in: npj vaccines Vol. 6; no. 1; p. 79
• Main Authors: Li, Leike, Freed, Daniel C., Liu, Yaping, Li, Fengsheng, Barrett, Diane F., Xiong, Wei, Ye, Xiaohua, Adler, Stuart P., Rupp, Richard E., Wang, Dai, Zhang, Ningyan, Fu, Tong-Ming, An, Zhiqiang
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 02.06.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 631/250/2152/2153/1291; 631/326/590/1867; Binding sites; Biomedical and Life Sciences; Biomedicine; Clinical trials; Cytomegalovirus; Infectious Diseases; Medical Microbiology; Monoclonal antibodies; Public Health; Vaccine; Vaccines; Virology
• ISSN: 2059-0105; 2059-0105
• DOI: 10.1038/s41541-021-00342-3

A conditionally replication-defective human cytomegalovirus (HCMV) vaccine, V160, was shown to be safe and immunogenic in a two-part, double-blind, randomized, placebo-controlled phase I clinical trial (NCT01986010). However, the specificities and functional properties of V160-elicited antibodies remain undefined. Here, we characterized 272 monoclonal antibodies (mAbs) isolated from single memory B cells of six V160-vaccinated subjects. The mAbs bind to diverse HCMV antigens, including multiple components of the pentamer, gB, and tegument proteins. The most-potent neutralizing antibodies target the pentamer-UL subunits. The binding sites of the antibodies overlap with those of antibodies responding to natural HCMV infection. The majority of the neutralizing antibodies target the gHgL subunit. The non-neutralizing antibodies predominantly target the gB and pp65 proteins. Sequence analysis indicated that V160 induced a class of gHgL antibodies expressing the HV1-18/KV1-5 germline genes in multiple subjects. This study provides valuable insights into primary targets for anti-HCMV antibodies induced by V160 vaccination.