Encephalitic alphavirus infection induces long-term humoral and cell-mediated responses in seropositive participants...

Encephalitic alphaviruses are an emerging viral threat with a history of large-scale outbreaks. Evaluating the immune response to natural infection in survivors is critical to the rational development of medical countermeasures (MCM), and yet little is known thus far. Here, we describe a comprehensive analysis of adaptive immune responses from a cohort of 37 convalescent seropositive individuals of Venezuelan equine encephalitis and/or Madariaga virus from Panama. We demonstrate persistent and polyfunctional B cell responses, as well as memory T cell cytokine production in response to viral antigen stimulation at least 3 years post-infection. VEEV survivors exhibit a higher proportion of strong responders with wider cross-reactivity than MADV survivors. This work illustrates the importance of a scientific focus on global health and international collaboration, explores several aspects of immunological engagement under-reported in the context of encephalitic alphaviruses, and should be leveraged to inform benchmarks for MCM evaluation and design.