Infection order outweighs the role of CD4+ T cells in tertiary flavivirus exposure

Nicole Marzan-Rivera, Crisanta Serrano-Collazo, Lorna Cruz, Petraleigh Pantoja, Alexandra Ortiz-Rosa, Teresa Arana, Melween I. Martinez, Armando G. Burgos, Chiara Roman, Loyda B. Mendez, Elizabeth Geerling, Amelia K. Pinto, James D. Brien, Carlos A. Sariol

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


The link between CD4+ T and B cells during immune responses to DENV and ZIKV and their roles in cross-protection during heterologous infection is an active area of research. Here we used CD4+ lymphocyte depletions to dissect the impact of cellular immunity on humoral responses during a tertiary flavivirus infection in macaques. We show that CD4+ depletion in DENV/ZIKV-primed animals followed by DENV resulted in dysregulated adaptive immune responses. We show a delay in DENV-specific IgM/IgG antibody titers and binding and neutralization in the DENV/ZIKV-primed CD4-depleted animals but not in ZIKV/DENV-primed CD4-depleted animals. This study confirms the critical role of CD4+ cells in priming an early effective humoral response during sequential flavivirus infections. Our work here suggests that the order of flavivirus exposure affects the outcome of a tertiary infection. Our findings have implications for understanding the complex flavivirus immune responses and for the development of effective flavivirus vaccines.

Original languageEnglish
Article number104764
Issue number8
StatePublished - Aug 19 2022

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  • Immunology
  • Virology

ASJC Scopus subject areas

  • General


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