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

Autor: Madani N; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA. navid_madani@dfci.harvard.edu.; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, 02115, USA. navid_madani@dfci.harvard.edu.; Department of Global Health and Social Medicine, Harvard Medical School, Boston, MA, 02115, USA. navid_madani@dfci.harvard.edu., Princiotto AM; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA., Mach L; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA., Ding S; Centre de Recherche du CHUM, Montreal, QC, H2X 0A9, Canada.; Department of Microbiology, Infectious Diseases and Immunology, Université de Montréal, Montreal, QC, H2X 0A9, Canada., Prevost J; Centre de Recherche du CHUM, Montreal, QC, H2X 0A9, Canada.; Department of Microbiology, Infectious Diseases and Immunology, Université de Montréal, Montreal, QC, H2X 0A9, Canada., Richard J; Centre de Recherche du CHUM, Montreal, QC, H2X 0A9, Canada.; Department of Microbiology, Infectious Diseases and Immunology, Université de Montréal, Montreal, QC, H2X 0A9, Canada., Hora B; Department of Medicine, Department of Immunology, Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC, 27710, USA., Sutherland L; Department of Medicine, Department of Immunology, Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC, 27710, USA., Zhao CA; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA., Conn BP; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA., Bradley T; Department of Medicine, Department of Immunology, Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC, 27710, USA., Moody MA; Department of Medicine, Department of Immunology, Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC, 27710, USA., Melillo B; Department of Chemistry, University of Pennsylvania, Philadelphia, PA, 19104, USA., Finzi A; Centre de Recherche du CHUM, Montreal, QC, H2X 0A9, Canada.; Department of Microbiology, Infectious Diseases and Immunology, Université de Montréal, Montreal, QC, H2X 0A9, Canada., Haynes BF; Department of Medicine, Department of Immunology, Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC, 27710, USA., Smith Iii AB; Department of Chemistry, University of Pennsylvania, Philadelphia, PA, 19104, USA. smithab@sas.upenn.edu., Santra S; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA., Sodroski J; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA. joseph_sodroski@dfci.harvard.edu.; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, 02115, USA. joseph_sodroski@dfci.harvard.edu.; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, 02115, USA. joseph_sodroski@dfci.harvard.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2018 Jun 18; Vol. 9 (1), pp. 2363. Date of Electronic Publication: 2018 Jun 18.
DOI: 10.1038/s41467-018-04758-9
Abstrakt: 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.
Databáze: MEDLINE