Boosting of HIV-1 Neutralizing Antibody Responses by a Distally Related Retroviral Envelope Protein.

Research output: Contribution to journalArticle

Abstract

Our knowledge of the binding sites for neutralizing Abs (NAb) that recognize a broad range of HIV-1 strains (bNAb) has substantially increased in recent years. However, gaps remain in our understanding of how to focus B cell responses to vulnerable conserved sites within the HIV-1 envelope glycoprotein (Env). In this article, we report an immunization strategy composed of a trivalent HIV-1 (clade B envs) DNA prime, followed by a SIVmac239 gp140 Env protein boost that aimed to focus the immune response to structurally conserved parts of the HIV-1 and simian immunodeficiency virus (SIV) Envs. Heterologous NAb titers, primarily to tier 1 HIV-1 isolates, elicited during the trivalent HIV-1 env prime, were significantly increased by the SIVmac239 gp140 protein boost in rabbits. Epitope mapping of Ab-binding reactivity revealed preferential recognition of the C1, C2, V2, V3, and V5 regions. These results provide a proof of concept that a distally related retroviral SIV Env protein boost can increase pre-existing NAb responses against HIV-1.

Details

Authors
  • Hannes Uchtenhagen
  • Torben Schiffner
  • Emma Bowles
  • Leo Heyndrickx
  • Celia LaBranche
  • Steven E Applequist
  • Marianne Jansson
  • Thushan De Silva
  • Jaap Willem Back
  • Adnane Achour
  • Gabriella Scarlatti
  • Anders Fomsgaard
  • David Montefiori
  • Guillaume Stewart-Jones
  • Anna-Lena Spetz
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Immunology in the medical area
Original languageEnglish
Pages (from-to)5802-5812
JournalJournal of Immunology
Volume192
Issue number12
Publication statusPublished - 2014
Publication categoryResearch
Peer-reviewedYes