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

@article{cohen2026encephalitic,
  title = {{Encephalitic alphavirus infection induces long-term humoral and cell-mediated responses in seropositive participants from Panama}},
  author = {Courtney A. Cohen and Jean Paul Carrera and Josefrancisco Galué and Davis Beltran and Rita Corrales and Luis Felipe Rivera and Zumara Chaverra and Yelissa Suarez and Jennifer Marciaga and Michelle L. Rock and Megan C. Ha and Darrell L. Wetzel and Erick V. O’Brien and Dafna Abelson and Zachary A. Bornholdt and Crystal L. Moyer and Larry Zeitlin and Juan M. Pascale and John M. Dye and Sandra López-Vergés and Andrew S. Herbert},
  journal = {PLOS Neglected Tropical Diseases},
  year = {2026},
  month = sep,
  doi = {10.1371/journal.pntd.0014660},
  url = {https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0014660},
  note = {CC BY 4.0},
}

TY  - JOUR
TI  - Encephalitic alphavirus infection induces long-term humoral and cell-mediated responses in seropositive participants from Panama
AU  - Courtney A. Cohen
AU  - Jean Paul Carrera
AU  - Josefrancisco Galué
AU  - Davis Beltran
AU  - Rita Corrales
AU  - Luis Felipe Rivera
AU  - Zumara Chaverra
AU  - Yelissa Suarez
AU  - Jennifer Marciaga
AU  - Michelle L. Rock
AU  - Megan C. Ha
AU  - Darrell L. Wetzel
AU  - Erick V. O’Brien
AU  - Dafna Abelson
AU  - Zachary A. Bornholdt
AU  - Crystal L. Moyer
AU  - Larry Zeitlin
AU  - Juan M. Pascale
AU  - John M. Dye
AU  - Sandra López-Vergés
AU  - Andrew S. Herbert
PY  - 2026
DA  - 2026/09/11
JO  - PLOS Neglected Tropical Diseases
DO  - 10.1371/journal.pntd.0014660
UR  - https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0014660
AB  - 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.
SN  - 1935-2735
ER  -