Abstract
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 language | English |
|---|---|
| Article number | 104764 |
| Journal | iScience |
| Volume | 25 |
| Issue number | 8 |
| DOIs | |
| State | Published - Aug 19 2022 |
Bibliographical note
Publisher Copyright:© 2022
Funding
This work would have not been possible without the dedication and commitment of the Caribbean Primate Research Center and the Animal Resources Center staff. We thank Dr. Leah C. Katzelnick and her student Guillermo Raimundi and Dr. Daniela Weiskopf for their valuable insights. The authors also recognize the support provided by Dr. Elmer Rodriguez in reviewing the statistics. Funding: This work was supported by R01AI148264 ( NIAID ) to C.A.S. and by P40 OD012217 to C.A.S. and M.I.M. (ORIP, OD, NIH ), and R25GM061838 to N.M.-R. Also, partial support was provided by Grant K22AI104794 to J.D.B. ( NIAID ). This work would have not been possible without the dedication and commitment of the Caribbean Primate Research Center and the Animal Resources Center staff. We thank Dr. Leah C. Katzelnick and her student Guillermo Raimundi and Dr. Daniela Weiskopf for their valuable insights. The authors also recognize the support provided by Dr. Elmer Rodriguez in reviewing the statistics. Funding: This work was supported by R01AI148264 (NIAID) to C.A.S. and by P40 OD012217 to C.A.S. and M.I.M. (ORIP, OD, NIH), and R25GM061838 to N.M.-R. Also, partial support was provided by Grant K22AI104794 to J.D.B. (NIAID). C.A.S. and N.M.-R. developed the experimental design. C.R. M.I.M. A.G.B. supervised and performed sample collection and animal monitoring. N.M.-R. C.S.-C. P.P. A.O.-R. L.C. E.G. T.A. and L.B.M. performed the experiments. N.M.-R, C.A.S. C.S.-C, E.G. J.D.B. and A.K.P. analyzed the data. N.M.-R. and C. A.S. drafted the article. C.A.S. N.M.-R. C.S.-C. L.C. P.P. A.O.-R. T.A. M.I.M. A.G.B. C.R. E.G. J.D.B. A.K.P. and L.B.M. reviewed and corrected the last version. The authors declare no competing interest.
| Funders | Funder number |
|---|---|
| Caribbean Primate Research Center | R01AI148264 |
| National Institutes of Health (NIH) | K22AI104794, R25GM061838 |
| National Institutes of Health (NIH) | |
| National Institute of Allergy and Infectious Diseases | P40 OD012217 |
| National Institute of Allergy and Infectious Diseases |
Keywords
- Immunology
- Virology
ASJC Scopus subject areas
- General
