Specificity and effector functions of non-neutralizing gB-specific monoclonal antibodies isolated from healthy individuals with human cytomegalovirus infection.

Published

Journal Article

Human cytomegalovirus (HCMV) is the most common congenital infection. A glycoprotein B (gB) subunit vaccine (gB/MF59) is the most efficacious clinically tested to date, having achieved 50% protection against primary infection of HCMV-seronegative women. We previously identified that gB/MF59 vaccination primarily elicits non-neutralizing antibody responses, with variable binding to gB genotypes, and protection associated with binding to membrane-associated gB. We hypothesized that gB-specific non-neutralizing antibody binding breadth and function are dependent on epitope and genotype specificity, and ability to interact with membrane-associated gB. We mapped twenty-four gB-specific monoclonal antibodies (mAbs) from naturally HCMV-infected individuals for gB domain specificity, genotype preference, and ability to mediate phagocytosis or NK cell activation. gB-specific mAbs were primarily specific for Domain II and demonstrated variable binding to gB genotypes. Two mAbs facilitated phagocytosis with binding specificities of Domain II and AD2. This investigation provides novel understanding on the relationship between gB domain specificity and antigenic variability on gB-specific antibody effector functions.

Full Text

Duke Authors

Cited Authors

  • Goodwin, ML; Webster, HS; Wang, H-Y; Jenks, JA; Nelson, CS; Tu, JJ; Mangold, JF; Valencia, S; Pollara, J; Edwards, W; McLellan, JS; Wrapp, D; Fu, T-M; Zhang, N; Freed, DC; Wang, D; An, Z; Permar, SR

Published Date

  • September 2020

Published In

Volume / Issue

  • 548 /

Start / End Page

  • 182 - 191

PubMed ID

  • 32838941

Pubmed Central ID

  • 32838941

Electronic International Standard Serial Number (EISSN)

  • 1096-0341

Digital Object Identifier (DOI)

  • 10.1016/j.virol.2020.07.009

Language

  • eng

Conference Location

  • United States