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

Author

Listed:
  • Navid Madani

    (Dana-Farber Cancer Institute
    Harvard Medical School
    Harvard Medical School)

  • Amy M. Princiotto

    (Dana-Farber Cancer Institute)

  • Linh Mach

    (Harvard Medical School)

  • Shilei Ding

    (Centre de Recherche du CHUM
    Université de Montréal)

  • Jérémie Prevost

    (Centre de Recherche du CHUM
    Université de Montréal)

  • Jonathan Richard

    (Centre de Recherche du CHUM
    Université de Montréal)

  • Bhavna Hora

    (Duke University Medical Center)

  • Laura Sutherland

    (Duke University Medical Center)

  • Connie A. Zhao

    (Dana-Farber Cancer Institute)

  • Brandon P. Conn

    (Harvard Medical School)

  • Todd Bradley

    (Duke University Medical Center)

  • M. Anthony Moody

    (Duke University Medical Center)

  • Bruno Melillo

    (University of Pennsylvania)

  • Andrés Finzi

    (Centre de Recherche du CHUM
    Université de Montréal)

  • Barton F. Haynes

    (Duke University Medical Center)

  • Amos B. Smith III

    (University of Pennsylvania)

  • Sampa Santra

    (Harvard Medical School)

  • Joseph Sodroski

    (Dana-Farber Cancer Institute
    Harvard Medical School
    Harvard T.H. Chan School of Public Health)

Abstract

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.

Suggested Citation

  • Navid Madani & Amy M. Princiotto & Linh Mach & Shilei Ding & Jérémie Prevost & Jonathan Richard & Bhavna Hora & Laura Sutherland & Connie A. Zhao & Brandon P. Conn & Todd Bradley & M. Anthony Moody & , 2018. "A CD4-mimetic compound enhances vaccine efficacy against stringent immunodeficiency virus challenge," Nature Communications, Nature, vol. 9(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04758-9
    DOI: 10.1038/s41467-018-04758-9
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