Immunogen Design for SARS-CoV-2

NIH Pandemic-Era Grants

Pandemic Era Grants

2024

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Principal Investigator: Tongqing  Zhou
Organization: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
Fiscal Year: 2024
Award: $284,935
Funding agency: National Institute of Allergy and Infectious Diseases

The SARS-CoV-2 spike is the basis of 1st-generation FDA-approved COVID-19 vaccines.

We anticipate the immunogenicity from wild-type or "2P"-stabilized spikes may not be optimal and are currently working to improve. In specific, we and others are working to define spike-based mechanisms by which SARS-CoV-2 evades the humoral immune response as well as to identify antibodies that are effective at preventing SARS-CoV-2 infection. Based on this developing insight, we are using antibody-guided structure-based design to develop domain-based and spike-based immunogens with these immune-evading mechanisms disabled so as to preferentially elicit potently neutralizing antibodies. 

We have coupled these domain-based and spike-based immunogens to highly immunogenic carrier proteins or self-assembling nanoparticles, as multivalent display often yields substantially higher immunogenicity than that of a single spike trimer.

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