HCMV trimer- and pentamer-specific antibodies synergize for virus neutralization but do not correlate with congenital transmission

Adam Vanarsdall, Andrea L. Chin, Jing Liu, Theodore S. Jardetzky, James Mudd, Susan Orloff, Daniel Streblow, Marisa M. Mussi-Pinhata, Aparecida Y. Yamamoto, Geraldo Duarte, William J. Britt, David Johnson

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Human cytomegalovirus (HCMV) causes substantial disease in transplant patients and harms the development of the nervous system in babies infected in utero. Thus, there is a major focus on developing safe and effective HCMV vaccines. Evidence has been presented that a major target of neutralizing antibodies (NAbs) is the HCMV pentamer glycoprotein gH/gL/UL128-131. In some studies, most of the NAbs in animal or human sera were found to recognize the pentamer, which mediates HCMV entry into endothelial and epithelial cells. It was also reported that pentamer-specific antibodies correlate with protection against transmission from mothers to babies. One problem with the studies on pentamer-specific NAbs to date has been that the studies did not compare the pentamer to the other major form of gH/gL, the gH/gL/gO trimer, which is essential for entry into all cell types. Here, we demonstrate that both trimer and pentamer NAbs are frequently found in human transplant patients’ and pregnant mothers’ sera. Depletion of human sera with trimer caused reductions in NAbs similar to that observed following depletion with the pentamer. The trimer- and pentamer-specific antibodies acted in a synergistic fashion to neutralize HCMV and also to prevent virus cell-to-cell spread. Importantly, there was no correlation between the titers of trimer- and pentamer-specific NAbs and transmission of HCMV from mothers to babies. Therefore, both the trimer and pentamer are important targets of NAbs. Nevertheless, these antibodies do not protect against transmission of HCMV from mothers to babies.

Original languageEnglish (US)
Pages (from-to)3728-3733
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume116
Issue number9
DOIs
StatePublished - Feb 26 2019

    Fingerprint

Keywords

  • Cell-to-cell spread
  • Congenital
  • Neutralizing antibodie
  • Transplant
  • Vaccines

ASJC Scopus subject areas

  • General

Cite this