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Determination of Molecular Structures of HIV Envelope Glycoproteins using Cryo-Electron Tomography and Automated Sub-tomogram Averaging
Published on: December 1, 2011
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Polyclonal antibody responses to HIV Env immunogens resolved using cryoEM
Aleksandar Antanasijevic1,2, Leigh M Sewall1,2, Christopher A Cottrell1,2
1Department of Integrative, Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.
Nature Communications
|August 11, 2021
Summary
Researchers evaluated HIV vaccine immunogens using cryo-electron microscopy with electron-particle electron microscopy (cryoEMPEM). This method rapidly maps antibody responses, revealing new immunogenic sites on BG505 SOSIP constructs.
Area of Science:
- Immunology
- Structural Biology
- Vaccine Development
Background:
- Engineered BG505 envelope glycoprotein trimers are key HIV vaccine candidates.
- Evaluating immunogenicity and antibody responses is crucial for vaccine efficacy.
Purpose of the Study:
- To assess the immunogenicity of stabilized BG505 SOSIP constructs in rhesus macaques.
- To develop and apply a high-resolution method for mapping polyclonal antibody responses.
- To investigate the neutralization potential of antibodies targeting specific epitopes.
Main Methods:
- Immunization of rhesus macaques with BG505 SOSIP trimers (free and nanoparticle-presented).
- Application of cryo-electron microscopy with electron-particle electron microscopy (cryoEMPEM) for antibody mapping.
- Mutational analysis and neutralization assays to assess epitope-specific antibody function.
Main Results:
- CryoEMPEM enabled rapid, high-resolution mapping of polyclonal antibody responses without monoclonal antibody isolation.
- Structurally distinct antibody classes binding overlapping sites were resolved.
- Commonly targeted epitopes, as well as epitopes on stabilizing mutations and glycosylation sites, were mapped.
Conclusions:
- CryoEMPEM is a powerful tool for analyzing antibody responses against complex immunogens like BG505 SOSIP.
- The study identified novel immunogenic epitopes, including those associated with stabilizing mutations and glycosylation.
- Findings contribute to the rational design of more effective HIV vaccines.
