Antibodies purified from sera of HIV-1-infected patients by affinity on the heptad repeat region 1/heptad repeat region 2 complex of gp41 neutralize HIV-1 primary isolates

AIDS. 2008 Oct 18;22(16):2075-85. doi: 10.1097/QAD.0b013e3283101260.

Abstract

Objective: The objective of this paper was to evaluate the presence and the neutralizing activity of antibodies directed against the complex formed between the two heptad repeat regions (HR1 and HR2) of HIV-1 gp41 in sera of HIV-1-infected patients.

Research designs and methods: The HR1 region was represented by the peptide N36 and the maltose-binding protein (MBP)-HR1, the HR2 region by the peptide C34 and MBP44. Antibodies directed to the HR1/HR2 complex were purified from sera by affinity chromatography using MBP-HR1/C34 adsorbed onto a resin.

Results: First, we demonstrated that human monoclonal antibodies, which are directed specifically to the HR1/HR2 complex recognized in enzyme-linked immunosorbent assay the MBP-HR1/C34 and MBP44/N36 mixtures but not the proteins or the peptides individually. We investigated the ability of 50 sera of HIV-1-infected patients to react with the MBP-HR1/C34 and MBP44/N36 complexes. We found that the majority of sera of HIV-1-infected patients recognized the HR1/HR2 complexes but not or to a lower extent the proteins or the peptides individually. Antibodies purified from sera by affinity chromatography using MBP-HR1/C34 adsorbed to a resin neutralized different primary HIV-1 isolates.

Conclusion: The presence of antibodies directed to the HR1/HR2 complex in sera of HIV-infected patients highlights the immunogenic character of the complex, whereas the neutralizing activity of these antibodies suggests that immunogens representing HIV-1 HR1/HR2 complexes might be used in anti-HIV vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / immunology
  • Carrier Proteins / immunology
  • Enzyme-Linked Immunosorbent Assay / methods
  • HIV Antibodies / blood*
  • HIV Antibodies / isolation & purification
  • HIV Envelope Protein gp41 / immunology*
  • HIV Infections / immunology*
  • HIV-1 / immunology*
  • HIV-1 / isolation & purification
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulin G / isolation & purification
  • Leucine Zippers / immunology
  • Maltose-Binding Proteins
  • Viral Envelope Proteins / immunology

Substances

  • Antibodies, Monoclonal
  • Carrier Proteins
  • HIV Antibodies
  • HIV Envelope Protein gp41
  • Immunoglobulin G
  • Maltose-Binding Proteins
  • Viral Envelope Proteins
  • gp41 protein, Human immunodeficiency virus 1