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

Abstract

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. Author summary: The impacts of globalization and climate change continue to promote the emergence and spread of infectious viral diseases. Although encephalitic alphaviruses have caused significant human outbreaks for decades, there are no approved therapeutics or vaccines available for human use. Much work has described the impact of various immune responses on the pathology of and recovery from alphavirus infection in animals, and yet little is known about immune responses in humans. Here we describe persistent humoral and cell-mediated memory responses in a cohort of convalescent seropositive human participants from the Darién region of Panama, where pathogenic alphaviruses regularly circulate in rural agricultural communities. We did not identify a specific immunological signature of recovery, but rather a diverse range of memory responses that may be associated with age upon infection, time post-infection, severity of clinical symptoms or co-morbidities. The baseline assessment of immune profiles of alphavirus survivors presented here, and the established framework of international collaboration and cooperation, offers an opportunity for future studies focused on understanding how specific immune responses may influence severity and persistence of clinical symptoms or impact protection from co-circulating alphaviruses, as well as informing rational anti-VEEV and broader anti-neurotropic alphaviruses therapeutic and vaccine design through targeted immune engagement.

Original publication: PLOS Neglected Tropical Diseases (2026-09-11). Source. Source DOI: 10.1371/journal.pntd.0014660.