Pre-clinical Vaccine and Antibody Development for Coronavirus Disease 2019 (COVID-19)

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During the past years, the Virology Laboratory has collaborated with other intramural NIAID labs and other external collaborators to develop a pseudovirus neutralization assay and an mRNA vaccine expressing the prefusion-stabilized SARS-CoV-2 spike trimer (mRNA-1273). For the neutralization assay, we have provided technical and software assistance to other VRC labs, and developed a shared Standard Operating Procedure. Since more SARS-CoV-2 variant viruses continuously arise in the world, we are continuously making various pseudoviruses corresponding to the emerging variant viruses. And more importantly, the pseudovirus neutralization assay also needed to be modified to adapted to the new variant viruses for the assay appropriate usage. The assay is being used by laboratory staff to evaluate human serum samples from individuals recovering from COVID-19 and from volunteers in the clinical trial of the Moderna mRNA1273 vaccine. We are also isolating and characterizing monoclonal antibodies from individuals recovering from COVID-19 disease, assessing for SARS-CoV-2 neutralizing antibodies, which are valuable research reagents with great potential for therapeutic and prevention purposes against the continuously emerging SARS-CoV-2 variants. For the mRNA vaccine, we show that mRNA-1273 induces potent neutralizing antibody responses to the initial strain and variant SARS-CoV-2, as well as high T cells responses. Importantly, this mRNA vaccine in the clinical trial have shown a robust neutralizing response to SARS-CoV-2. We are testing various new designs of non-infectious self-assembly Virus-Like-Particle (VLP) expressing the SARS-CoV-2 spike on the particles' surface as a potential vaccine which may elicit better antibodies. Since the mRNA vaccine has proved to be a highly successful vaccine platform, we will continue to develop the VLP vaccine candidates in genetic (mRNA or DNA) platform.