Pre-clinical Vaccine Development for Emerging and Re-emerging Infectious Diseases

NIH Pandemic-Era Grants

Pandemic Era Grants

2024

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Principal Investigator: Wing Pui  Kong
Organization: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
Fiscal Year: 2024
Award: $912,113
Funding agency: National Institute of Allergy and Infectious Diseases

The Virology Core has collaborated with other intramural NIAID labs help to develop a pan-coronaviruses spike protein subunit vaccine and re-emerging infectious diseases.  

During the past year, we focused on developing the potent SARS-CoV2 vaccine against most recent SARA-CoV2 variants. We successfully designed and expressed some hybrid immunogens of the SARS-CoV2 Spike RBD  fused with SARS-CoV1 spike tandemly into one protein immunogen. The hybrid immunogens contained both epitopes of the two sarbecoviruses in one protein. Various mutations at different regions at the spikes proteins were evaluated for broadening binding of different SARs-CoV2 variants. We produced and assessed self-assembling nanoparticles displaying RBDs from WA1 and BA.5 strains by using the SpyTag:SpyCatcher system for coupling. Murine immunizations revealed that the stabilized RBD-nanoparticles induced ~100-fold higher autologous neutralization titers than the prefusion-stabilized (S2P) spike. Assessment against a panel of β-coronavirus variants revealed both the stabilized BA.5-RBD nanoparticle and the stabilized WA1-BA.5-(mosaic)-RBD nanoparticle to elicit much higher neutralization breadth than the stabilized WA1-RBD nanoparticle. The extraordinary titer and high neutralization breadth elicited by stabilized RBD nanoparticles from strain BA.5 make them strong candidates for next-generation COVID-19 vaccines.

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