Improved Elicitation of Neutralizing Antibodies against Primary Human Immunodeficiency Viruses by Soluble Stabilized Envelope Glycoprotein Trimers

Author:

Yang Xinzhen12,Wyatt Richard13,Sodroski Joseph124

Affiliation:

1. Department of Cancer Immunology & AIDS, Dana-Farber Cancer Institute,1

2. Department of Pathology2 and

3. Department of Medicine,3 Harvard Medical School, and

4. Department of Immunology and Infectious Diseases, Harvard School of Public Health,4Boston, Massachusetts 02115

Abstract

ABSTRACT Human immunodeficiency virus (HIV-1) envelope glycoprotein subunits, such as the gp120 exterior glycoprotein, typically elicit antibodies that neutralize T-cell-line-adapted (TCLA), but not primary, clinical isolates of HIV-1. Here we compare the immunogenicity of gp120 and soluble stabilized trimers, which were designed to resemble the functional envelope glycoprotein oligomers of primary and TCLA HIV-1 strains. For both primary and TCLA virus proteins, soluble stabilized trimers generated neutralizing antibody responses more efficiently than gp120 did. Trimers derived from a primary isolate elicited antibodies that neutralized primary and TCLA HIV-1 strains. By contrast, trimers derived from a TCLA isolate generated antibodies that neutralized only the homologous TCLA virus. Thus, soluble stabilized envelope glycoprotein trimers derived from primary HIV-1 isolates represent defined immunogens capable of eliciting neutralizing antibodies that are active against clinically relevant HIV-1 strains.

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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