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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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Ability of nucleoside-modified mRNA to encode HIV-1 envelope trimer nanoparticles
Zekun Mu1, Kevin Wiehe2,3, Kevin O Saunders1,2,4,5
1Department of Immunology, Duke University School of Medicine, Durham, NC, 27710, USA.
Biorxiv : the Preprint Server for Biology
|August 17, 2021
Summary
Messenger RNA (mRNA) lipid nanoparticles can now encode complex HIV-1 nanoparticle immunogens. This advance enables the development of novel HIV vaccines targeting broadly neutralizing antibody precursor B cells.
Area of Science:
- Vaccinology
- Immunology
- Molecular Biology
Background:
- Nucleoside-modified messenger RNAs (mRNAs) in lipid nanoparticles (LNPs) have revolutionized vaccine development, as seen with COVID-19 vaccines.
- For Human Immunodeficiency Virus type 1 (HIV-1) vaccine design, multivalent envelope (Env) trimer protein nanoparticles are more effective immunogens than trimers alone for initiating broadly neutralizing antibody (bnAb) B cell lineages.
Approach:
- This study demonstrates the successful expression of complex multivalent nanoparticle immunogens using mRNA technology.
- Researchers engineered mRNAs to encode antigenic Env trimers displayed on ferritin nanoparticles.
- The immunogens were tested in bnAb precursor VH + VL knock-in mice to assess their immunogenicity.
Key Points:
- mRNA-LNP encoded nanoparticle immunogens successfully initiated bnAb precursor B cell expansion in mice.
- The approach induced serum autologous tier 2 neutralizing activity.
- Next-generation sequencing revealed the acquisition of critical mutations in the antibodies generated, and monoclonal antibodies capable of neutralizing heterologous HIV-1 isolates were successfully isolated.
Conclusions:
- Messenger RNA-lipid nanoparticle (mRNA-LNP) technology can effectively encode complex immunogens for vaccine development.
- This platform is promising for designing germline-targeting and sequential boosting immunogens for future HIV-1 vaccines.
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