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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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Structure and immunogenicity of a stabilized HIV-1 envelope trimer based on a group-M consensus sequence
Kwinten Sliepen1, Byung Woo Han2,3, Ilja Bontjer1
1Department of Medical Microbiology, Amsterdam Infection & Immunity Institute, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, Amsterdam, 1105AZ, The Netherlands.
Nature Communications
|May 31, 2019
Summary
A novel consensus HIV-1 envelope (Env) trimer, ConM, was engineered to improve vaccine design. This stabilized ConM trimer elicits potent neutralizing antibody responses, offering a promising strategy for developing effective HIV-1 vaccines.
Area of Science:
- Virology
- Immunology
- Vaccine Development
Background:
- Stabilized HIV-1 envelope glycoproteins (Env) are crucial for vaccines inducing broadly neutralizing antibodies (bNAbs).
- Rare isolate-specific antigenic residues can limit vaccine efficacy.
- A consensus sequence approach aims to present conserved epitopes for broader immune responses.
Purpose of the Study:
- To engineer a stabilized HIV-1 Env trimer based on a consensus sequence (ConM) of group M isolates.
- To characterize the ConM trimer's structure and antigenic properties.
- To evaluate the immunogenicity of the ConM trimer in eliciting neutralizing antibody (NAb) responses.
Main Methods:
- Generation of a SOSIP trimer based on the ConM sequence.
- Crystal structure determination of the ConM trimer.
- Immunization of rabbits and macaques with the ConM trimer, including presentation on ferritin nanoparticles.
- Assessment of NAb responses against autologous virus.
Main Results:
- The ConM trimer's crystal structure resembles native Env trimers, with a surface displaying few rare residues.
- The ConM trimer elicits strong autologous NAb responses in immunized animals.
- Nanoparticle presentation significantly enhances NAb responses.
- Dominant NAb specificity targets the trimer apex epitope.
Conclusions:
- Consensus-based immunogens, like the ConM trimer, are valuable for HIV-1 vaccine design.
- The ConM trimer presents conserved epitopes effectively, eliciting potent NAb responses.
- This strategy may be applicable to developing vaccines against other viruses.
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