Acute induction of IFNa is responsible for the attenuation of the live measles vaccine: rmTEC data
The aim of the study with which this data is associated, is to provide a molecular model of LAMV (the live-attenuated measles vaccine) attenuation that could help improve vaccine uptake and inform rational vaccine design. Our study leverages both in vitro and in vivo models of infection to find that acute induction of innate immunity in immune cells is the critical determinant of LAMV attenuation. We show that LAMV, in contrast to pathogenic wild type measles virus (MeV), causes a strong IFNa response in primary human peripheral blood mononuclear cells, which restricts viral replication and spread in a post-entry manner. LAMV can enter, transcribe viral mRNA and translate viral proteins in immune cells, but is not able to form infectious particles and spread from cell to cell. Specifically, we find that mutations conserved across LAMV strains in the P/V/C and H genes contribute to the induction of IFNa and the restriction of infectious virus production. In PBMC cultures and in rhesus macaques, LAMV infection also results in the early acute induction of proinflammatory cytokines that likely play a role in the excellent immunogenicity of the vaccine. Overall, our study provides a virological and immunological framework for LAMV attenuation which can be leveraged in repurposing the LAMV backbone and in future vaccine design.