Development of Nipah virus mRNA vaccine

National Institute Of Allergy And Infectious Diseases

Investigators

Abstract

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 follow-up studies (study VRC-22-0989-amended and VRC-24-1043) in African Green Monkeys (AGM) to evaluate the same mRNA-1215 vaccine used in a phase I human clinical trial (VRC322) in order to establish and test immune correlates and mechanism of protection against NiV infection. For VRC322, we have completed all experiments evaluating primary, secondary and exploratory study objectives and submitted a manuscript detailing our study findings to Nature Medicine. For VRC-22-0989-amended and VRC-24-1043, we used high-throughput NiV ELISA binding, pseudotyped virus neutralization assays, and B- and T-cell assays to assess binding, neutralization and specificity of the immune response to mRNA-1215. We demonstrated that prime-boost with low dose (0.02 mcg) mRNA-1215 is protective against NiV challenge. We also demonstrated that prime-boost with mRNA-1215 provides complete protection against Hendra virus (HeV), a related Henipavirus. Additionally, we demonstrated that a single dose of mRNA-1215 is sufficient to protect against NiV challenge. Finally, we also demonstrated that passive transfer of mRNA-1215-elicited IgG is sufficient to protect against NiV challenge.