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Conformational Evaluation of HIV-1 Trimeric Envelope Glycoproteins Using a Cell-based ELISA Assay
Published on: September 14, 2014
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Neutralization tiers of HIV-1
David C Montefiori1, Mario Roederer2, Lynn Morris3
1Department of Surgery, Duke University Medical Center, Durham, North Carolina.
Current Opinion in HIV and AIDS
|December 22, 2017
Summary
Understanding HIV-1 neutralization tiers is key for vaccine development. This study reveals that the dynamic conformations of HIV-1 envelope glycoproteins explain neutralization phenotypes, guiding better antibody response assessments.
Area of Science:
- Virology
- Immunology
- Structural Biology
Background:
- HIV-1 isolates are classified by neutralization 'tier' phenotypes.
- Tier classification impacts monitoring and interpretation of vaccine-elicited neutralizing antibody responses.
- The molecular basis for HIV-1 neutralization phenotypes has been unclear.
Purpose of the Study:
- To present a model explaining HIV-1 neutralization phenotypes based on envelope glycoprotein dynamics.
- To describe a new approach for ranking HIV-1 vaccine-elicited neutralizing antibody responses.
Main Methods:
- Analysis of HIV-1 envelope glycoprotein conformations.
- Correlation of conformational states with neutralization tier phenotypes.
- Development of a novel antibody response ranking method.
Main Results:
- HIV-1 envelope glycoprotein trimers transition through multiple conformations.
- Neutralization tiers (1A, 1B, 2, 3) correlate with trimer conformational states (open, intermediate, closed).
- Closed conformations are stabilized by broadly neutralizing antibodies and are typical of tier 2 viruses.
Conclusions:
- The dynamic nature of HIV-1 envelope glycoproteins and epitope exposure explains neutralization phenotypes.
- Tier 2 viruses, with closed conformations, are a priority target for vaccines.
- Caution is advised when interpreting tier 1A neutralization assays due to non-protective antibody specificities.
