Core D: Animal Immunogenicity and Challenge

SUMMARY Flaviviruses and alphaviruses are emerging arthropod-borne viruses that cause severe and often life-threatening disease in humans, and ongoing and recent epidemics have infected millions of people and threaten global health. Currently, no specific treatment is available for any flavivirus or alphavirus, and licensed vaccines are

available for only a few flaviviruses. Given their global health burden, the worldwide spread of mosquito vectors, and expanded global travel, there is a pressing need for the development of countermeasures against these viruses. The major goal of the Flavivirus and Alphavirus ReVAMPP (FLARE) Center is to establish ‘plug-and-

play’ modular platforms with optimized design technologies for vaccines and antibody therapeutics against prototype alphaviruses and flaviviruses that can be readily applied to newly emerging related threats with pandemic potential. Research in our Animal Vaccination, Immunogenicity and Challenge Model Core D

(hereafter, Core D) will use proven animal models for the secondary down-selection of prioritized vaccine candidates generated by Projects 1-4 and lead monoclonal antibodies generated by Project 5 directed against a diverse group of highly pathogenic flaviviruses (Dengue, West Nile, and tick-borne encephalitis viruses) and

alphaviruses (Chikungunya and Venezuelan equine encephalitis viruses) to be used as models for future emerging agents. Core D will also support the testing of late-stage “sprints” including a vaccine against western equine encephalitis virus and mAb combinations against Mayaro virus to validate the modular platforms. Core

D is led by Dr. Streblow with key contributions by Drs. Diamond, Klimstra, Morrison, Rossi, Freiberg, and Shresta. This team of investigators contains the world’s leading experts in alphavirus and flavivirus animal model development and viral pathogenesis with substantial experience in vaccine and therapeutic testing. With input

from other FLARE Center members, Core D will coordinate experimental design, animal usage, vaccine/mAb type and dosage, sample collection and distribution as well as perform immunogenicity and challenge studies. Core D will standardize delivery modes, challenge strains, animal care, blood draw timing and processing, and

necropsy procedures. This coordinated approach will provide the Projects with consistent data of the highest quality that can be cross-compared. The data generated in Core D will be provided back to the Projects and Core B as well as Core E to assess correlates of protection and identify optimal platforms and antigen designs

for preparedness against future emerging flavivirus and alphavirus pandemic threats.