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

Leike Li, Daniel C. Freed, Yaping Liu, Fengsheng Li, Diane F. Barrett, Wei Xiong, Xiaohua Ye, Stuart P. Adler, Richard E. Rupp, Dai Wang, Ningyan Zhang, Tong Ming Fu, Zhiqiang An

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number79
Journalnpj Vaccines
Volume6
Issue number1
DOIs
StatePublished - Dec 2021

ASJC Scopus subject areas

  • Immunology
  • Pharmacology
  • Infectious Diseases
  • Pharmacology (medical)

Fingerprint

Dive into the research topics of 'A conditionally replication-defective cytomegalovirus vaccine elicits potent and diverse functional monoclonal antibodies in a phase I clinical trial'. Together they form a unique fingerprint.

Cite this