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Principal Investigator: Rosemarie Mason
Organization: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
Fiscal Year: 2024
Award: $1,317,404
Funding agency: National Institute of Allergy and Infectious Diseases
This project is part of a systematic Nipah virus (NiV) program aimed at evaluating a candidate NiV vaccine (mRNA-1215) that has advanced to a Phase I clinical trial (study VRC322). We conducted a pilot study (study VRC-22-0989) in African Green Monkeys (AGM) to demonstrate that the mRNA-1215 vaccine used in VRC322 can elicit protection against a lethal challenge with NiV. We determined that mRNA-1215 was protective against lethal NiV challenge for all doses (2, 10 or 50 mcg) and prime-boost intervals (4-week or 12-week) tested. However, we were unable to identify candidate immune correlates of protection against NiV infection. Therefore, we initiated follow-up studies (study VRC-22-0989-amended and VRC-24-1043) aimed at establishing and testing immune correlates and mechanism of protection against NiV infection.
For VRC322, we have completed assessment of secondary objectives to evaluate antibody responses to the mRNA-1215 vaccine at various doses (10, 25, 50 or 100 mcg) at 2 weeks after last product administration. We have also completed exploratory objectives to evaluate the specificity and functionality of mRNA-1215 vaccine-induced antibodies and the immune response in all study groups at various timepoints. Experiments to evaluate the frequency, magnitude, phenotype, and specificity of B-and T-cell responses at various time points throughout the study are ongoing.
Finally, we used the high-throughput NiV ELISA binding and pseudotyped virus neutralization assays which we developed and optimized to help establish the first International Standard for NiV, the results of which are included in the World Health Organization (WHO) report WHO/BS/2023.2458 WHO 1st International Standard for Nipah virus antibody.
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