A CD4-mimetic compound enhances vaccine efficacy against stringent immunodeficiency virus challenge.

Published online

Journal Article

The envelope glycoprotein (Env) trimer ((gp120/gp41)3) mediates human immunodeficiency virus (HIV-1) entry into cells. The "closed," antibody-resistant Env trimer is driven to more open conformations by binding the host receptor, CD4. Broadly neutralizing antibodies that recognize conserved elements of the closed Env are potentially protective, but are elicited inefficiently. HIV-1 has evolved multiple mechanisms to evade readily elicited antibodies against more open Env conformations. Small-molecule CD4-mimetic compounds (CD4mc) bind the HIV-1 gp120 Env and promote conformational changes similar to those induced by CD4, exposing conserved Env elements to antibodies. Here, we show that a CD4mc synergizes with antibodies elicited by monomeric HIV-1 gp120 to protect monkeys from multiple high-dose intrarectal challenges with a heterologous simian-human immunodeficiency virus (SHIV). The protective immune response persists for at least six months after vaccination. CD4mc should increase the protective efficacy of any HIV-1 Env vaccine that elicits antibodies against CD4-induced conformations of Env.

Full Text

Duke Authors

Cited Authors

  • Madani, N; Princiotto, AM; Mach, L; Ding, S; Prevost, J; Richard, J; Hora, B; Sutherland, L; Zhao, CA; Conn, BP; Bradley, T; Moody, MA; Melillo, B; Finzi, A; Haynes, BF; Smith Iii, AB; Santra, S; Sodroski, J

Published Date

  • June 18, 2018

Published In

Volume / Issue

  • 9 / 1

Start / End Page

  • 2363 -

PubMed ID

  • 29915222

Pubmed Central ID

  • 29915222

Electronic International Standard Serial Number (EISSN)

  • 2041-1723

Digital Object Identifier (DOI)

  • 10.1038/s41467-018-04758-9

Language

  • eng

Conference Location

  • England