Distinct Immunoglobulin Fc Glycosylation Patterns Are Associated with Disease Nonprogression and Broadly Neutralizing Antibody Responses in Children with HIV Infection

Research output: Contribution to journalJournal articleResearchpeer-review

Documents

  • M. Muenchhoff
  • A. W. Chung
  • J. Roider
  • Anne Sophie Dugast
  • Simone Richardson
  • Kløverpris, Henrik Nyhus
  • Alasdair Leslie
  • Thumbi Ndung’u
  • Penny Moore
  • Galit Alter
  • Philip J.R. Gouldera

A prophylactic HIV vaccine would ideally induce protective immunity prior to sexual debut. Children develop broadly neutralizing antibody (bnAb) responses faster and at higher frequencies than adults, but little is known about the underlying mechanisms or the potential role of Fc-mediated effector functions in disease progression. We therefore performed systems immunology, with immunoglobulin profiling, on HIV-infected children with progressive and nonprogressive disease. Pediatric nonprogressors (PNPs) showed distinct immunoglobulin profiles with an increased ability to elicit potent Fc-mediated natural killer (NK)-cell effector functions. In contrast to previous reports in adults, both groups of children showed high levels of gp120-specific IgG Fc glycan sialylation compared to bulk IgG. Importantly, higher levels of Fc glycan sialylation were associated with increased bnAb breadth, providing the first evidence that Fc sialylation may drive affinity maturation of HIV-specific antibodies in children, a mechanism that could be exploited for vaccination strategies.

Original languageEnglish
Article numbere00880-20
JournalmSphere
Volume5
Issue number6
Pages (from-to)1-16
ISSN2379-5042
DOIs
Publication statusPublished - 2020

Bibliographical note

Publisher Copyright:
© 2020 Muenchhoff et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

    Research areas

  • broadly neutralizing antibodies (bnAbs), Fc effector functions, Fc glycosylation, HIV, nonneutralizing antibodies, pediatric, vaccine

ID: 271603736