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

Nat Commun. 2018 Jun 18;9(1):2363. doi: 10.1038/s41467-018-04758-9.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS Vaccines / immunology*
  • Animals
  • Drug Evaluation, Preclinical
  • Guanidines / chemistry
  • Guanidines / pharmacology*
  • HEK293 Cells
  • HIV Envelope Protein gp120 / immunology*
  • Humans
  • Immunity, Heterologous
  • Immunization
  • Indenes / chemistry
  • Indenes / pharmacology*
  • Lentiviruses, Primate / drug effects*
  • Macaca mulatta


  • AIDS Vaccines
  • BNM-III-170
  • Guanidines
  • HIV Envelope Protein gp120
  • Indenes
  • gp120 protein, Human immunodeficiency virus 1