Comparing Human Pediatric Immune Responses to Primary Infection with Dengue, Chikungunya and Zika Viruses

Lewis Elwood Tomalin¹Sandra Bos²Rafael Fenutria¹Yitong Chen¹Seunghee Kim-schulze¹Adeeb H Rahman¹Angel Balmaseda³Ana Fernandez-Sesma¹Eva Harris^2*Mayte Suarez-Farinas^1*

• ¹Icahn School of Medicine at Mount Sinai, New York, United States
• ²University of California Berkeley, Berkeley, United States
• ³Laboratorio Nacional de Virología, Centro Nacional de Diagnóstico y Referencia, Ministerio de Salud, Managua, Nicaragua, Managua, Nicaragua

The four dengue virus serotypes (DENV1-4), Zika virus (ZIKV) and chikungunya virus (CHIKV) have similar epidemiology and transmission cycles and are the most prevalent arthropod-borne viruses in humans, with half the world's population at risk of infection. Although clinical symptoms are similar and often mild, all three viruses can lead to severe and life-threatening complications that differ among the three viruses. We characterized the immune responses to DENV, ZIKV and CHIKV by measuring cytokine/chemokine/growth-factor profiles in plasma/serum samples, and immune-cell profiles in peripheral blood mononuclear cells, collected from children during acute (~1-3 days) primary infection with DENV1/DENV3 (n=32), ZIKV (n=50) or CHIKV (n=45), and during infection recovery (~14-21 days). The innate immune responses to CHIKV and DENV were similar in terms of acute cytokine concentrations and monocyte frequencies. The innate immune response to ZIKV was mild, and the adaptive response was delayed, showing much lower concentrations of inflammatory cytokines and delayed T-cell/B-cell activation. Overall, the immune response to CHIKV and DENV were most similar, despite DENV and ZIKV belonging to the same flavivirus genus. Immune response to ZIKV was the most distinct, showing rapid B-cell expansion but attenuated/delayed B-cell activation. These findings highlight distinct immune responses to arbovirus infection.