Immune checkpoint modulation enhances HIV-1 antibody induction.

Published online

Journal Article

Eliciting protective titers of HIV-1 broadly neutralizing antibodies (bnAbs) is a goal of HIV-1 vaccine development, but current vaccine strategies have yet to induce bnAbs in humans. Many bnAbs isolated from HIV-1-infected individuals are encoded by immunoglobulin gene rearrangments with infrequent naive B cell precursors and with unusual genetic features that may be subject to host regulatory control. Here, we administer antibodies targeting immune cell regulatory receptors CTLA-4, PD-1 or OX40 along with HIV envelope (Env) vaccines to rhesus macaques and bnAb immunoglobulin knock-in (KI) mice expressing diverse precursors of CD4 binding site HIV-1 bnAbs. CTLA-4 blockade augments HIV-1 Env antibody responses in macaques, and in a bnAb-precursor mouse model, CTLA-4 blocking or OX40 agonist antibodies increase germinal center B and T follicular helper cells and plasma neutralizing antibodies. Thus, modulation of CTLA-4 or OX40 immune checkpoints during vaccination can promote germinal center activity and enhance HIV-1 Env antibody responses.

Full Text

Duke Authors

Cited Authors

  • Bradley, T; Kuraoka, M; Yeh, C-H; Tian, M; Chen, H; Cain, DW; Chen, X; Cheng, C; Ellebedy, AH; Parks, R; Barr, M; Sutherland, LL; Scearce, RM; Bowman, CM; Bouton-Verville, H; Santra, S; Wiehe, K; Lewis, MG; Ogbe, A; Borrow, P; Montefiori, D; Bonsignori, M; Anthony Moody, M; Verkoczy, L; Saunders, KO; Ahmed, R; Mascola, JR; Kelsoe, G; Alt, FW; Haynes, BF

Published Date

  • February 19, 2020

Published In

Volume / Issue

  • 11 / 1

Start / End Page

  • 948 -

PubMed ID

  • 32075963

Pubmed Central ID

  • 32075963

Electronic International Standard Serial Number (EISSN)

  • 2041-1723

Digital Object Identifier (DOI)

  • 10.1038/s41467-020-14670-w

Language

  • eng

Conference Location

  • England