Flaviviruses and alphaviruses are enveloped, single-stranded RNA viruses that cause epidemics of human disease on a global scale, with new family members regularly emerging and causing severe disease. The major goal of our Flavivrus and Alphavirus ReVAMPP (FLARE) Center is to establish optimized design and modular ‘plug-and-play’ technologies for vaccines and antibody therapeutics against prototype flaviviruses and alphaviruses that can be readily applied to newly emerging related threats in this family with pandemic potential. Research in the Correlates of Protection Core E (hereafter, Core E) will use “state-of-the art” immune assays to evaluate vaccine and monoclonal antibody efficacy and safety against a diverse group of highly pathogenic flaviviruses (DENV, WNV, and TBEV) and alphaviruses (CHIKV and VEEV) as models for future emerging agents. Core E, led by Drs. Diamond and DeSilva, with key contributions by Drs. Cherry, Wang, Shresta, Katzelnick, and Goss, will meet this need by establishing high-throughput virological and immunological assays to assess potency, breadth and safety of vaccine responses and monoclonal antibodies. Core E also will leverage the testing of archived clinical specimens from human arbovirus cohort studies and vaccine trials to validate, benchmark, and improve existing assays, and to develop new assays. The main mission of Core E will be to support and guide the five Research Projects and Animal Core D by functionally interrogating monoclonal antibodies and serum samples from vaccinated animals. Core E also will perform univariate and multivariate regression analysis on assimilated data to define key immune correlates of protection or enhancement for different flaviviruses and alphavirus vaccine platforms. Establishing the immune correlates of protection in animals and their relationship to humans will guide Go/No-Go decisions in the individual Projects and inform the rapid development of protective vaccines and antibodies against future emerging flaviviruses and alphaviruses.