Development of a COVID Vaccine Model in NHP

NIH Pandemic-Era Grants

Pandemic Era Grants

2022

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Principal Investigator: ROBERT A SEDER
Organization: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
Fiscal Year: 2022
Award: $332,304
Funding agency: National Institute of Allergy and Infectious Diseases

NHP immunized with 10 and 100g of mRNA-1273 encoding the SARS CoV2 had robust neutralizing antibodiy titers following two immunizations.  mRNA-1273 induced Th1-biased CD4 T cell responses and low or undetectable Th2 or CD8 T responses.  Following an infectious challenge with SARS CoV2 by the intranasal (IN) or intratracheal route (IT), there is no detectable viral replication in the bronchoalveolar lavage (BAL) by day 2 following challenge in 7 out of 8 NHPs, in both 10 and 100 g mRNA-1273-immunized groups and no detectable viral replication in nasal swabs (NS) of all 8 NHPs immunized with 100 g mRNA-1273 by day 2 post-challenge. There was limited inflammation and no detectable virus in the lungs of either vaccine group.  mRNA-1273 vaccination induces robust SARS CoV-2 S neutralizing activity and rapid protection in the upper and lower airways with absence of lung immunopathology in NHP. 

Over the past year we have defined the immune correlates of protection by the mRNA 1273 vaccine in NHP. These data showed that there protection in the lower airway requires less antibody than the upper airway. We have also demonstrated that two doses of mRNA 1273 are optimal for mediating protection against the Beta variant of concern. In addition we have shown that boosting NHP 6 months after their primary immunization with mRNA 1273 leads to significant increase in neutralizing antibodies and protection in the upper and lower airway against the Beta variant.

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