Immunogen Design and Development for the Disease X Vaccine Library

This is a pre-proposal type submission in which a high-level summary of planned activities is proposed. The Methodist team will develop vaccine candidates for diseases caused by emerging viruses of interest to CEPI: Lassa virus (LASV), and Nipah virus (NiV). UTMB will perform neutralization assays for both viruses, as well as test vaccine candidates in rodent and non-human primate models within the ABSL-4 facilities. Immunogenicity will be assessed following intramuscular doses of mRNA vaccines, using IgM and IgG ELISA as well as plaque reduction neutralization tests (PRNT). After challenge, animals will be bled at key time points and rises in antibody titers will be assessed to evaluate potential sterilizing immunity following vaccination. Safety of the vaccines will be assessed by following body weights and clinical scores (based on posture and behavior) of vaccinated animals with sham-vaccinated or positive control vaccines (if available) with known human or NHP safety profiles. Efficacy will be evaluated after challenge with virus doses known to produce fatality or measurable disease in the models, such as weight loss, fever and viremia. Following evaluation of up to IO candidates in rodents, up to two vaccine candidates per virus will be selected for immunogenicity and efficacy testing in an NHP model. The design of these experiments will be similar to that used for rodents except that cohort sizes will be adjusted to the minimum required to have 80% power to show a reduction in mortality, fever measured with temperature loggers implanted in the animals for nearly continuous monitoring, viremia, and clinical signs of disease based on a semi-quantitative scoring system.