Post exposure vaccines gainst emerging viruses – EXPUNGER

The current pandemic reminds us the necessity to be prepared for the emergence and re-emergence of human pathogens. The World Health Organization has established a list of priority diseases posing the greatest public health risk due to their epidemic potential and requiring massive research effort towards the development of efficient countermeasures. Among these diseases is Lassa fever (LF), a viral hemorrhagic fever caused by Lassa virus (LASV). LASV is responsible for thousands of deaths each year in Western Africa, but is also the most exported hemorrhagic fever virus. To date, there is no effective treatment or vaccine against LF. We have generated MeV-GPC+NPExoN, a measles-based vaccine expressing LASV antigens that protects cynomolgus monkeys against LF up to a year after vaccination and that is currently in evaluation in clinical trials. Transcriptome analyses of peripheral blood mononuclear cells collected in the early days after vaccination revealed a strong activation of the innate response in immunized monkeys that persists for up to 7 days and is correlated to protection efficacy. This observation prompted us to evaluate the efficacy of MeV-GPC+NPExoN as a post exposure vaccine. Indeed, it is believed that post exposure protection induced by vaccination is conferred by an early innate response that slows down the infection to allow the mounting of an adaptive immune response. But this hypothesis has not been clearly demonstrated and it has even been suggested that an early non-specific innate response may be sufficient to control infection. We propose to test this hypothesis by assessing the innate and adaptive responses following post exposure vaccination in our monkey model of LF using three vaccines: a vaccine inducing innate immunity but expressing no LASV antigens; a vaccine inducing innate immunity and expressing LASV antigens; and a vaccine inducing poorly innate immunity but expressing LASV antigens. The timing of the immune response is also crucial in post exposure vaccination and delayed vaccination may fail to expunge the infection. To determine the time window of post exposure efficacy against LF, we will also test the efficacy of MeV-GPC+NPExoN when given at different times after a LASV infection, with the goal to determine its potential as a therapeutic vaccine.