Potential role of heterologous flavivirus immunity in preventing urban transmission of yellow fever virus

Divya P. Shinde, Jessica A. Plante, Dionna Scharton, Brooke Mitchell, Jordyn Walker, Sasha R. Azar, Rafael K. Campos, Lívia Sacchetto, Betânia P. Drumond, Nikos Vasilakis, Kenneth S. Plante () and Scott C. Weaver ()
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Divya P. Shinde: University of Texas Medical Branch
Jessica A. Plante: University of Texas Medical Branch
Dionna Scharton: University of Texas Medical Branch
Brooke Mitchell: University of Texas Medical Branch
Jordyn Walker: University of Texas Medical Branch
Sasha R. Azar: University of Texas Medical Branch
Rafael K. Campos: University of Texas Medical Branch
Lívia Sacchetto: São José do Rio Preto
Betânia P. Drumond: Universidade Federal de Minas Gerais
Nikos Vasilakis: University of Texas Medical Branch
Kenneth S. Plante: University of Texas Medical Branch
Scott C. Weaver: University of Texas Medical Branch

Nature Communications, 2024, vol. 15, issue 1, 1-11

Abstract: Abstract During the recent yellow fever (YF) epidemics in Brazil, human cases were attributed to spillover infections via sylvatic mosquito transmission. Despite YF virus (YFV) transmission in major urban centers with insufficient vaccination coverage and abundant populations of the domestic vector, Aedes aegypti, there was no evidence of human-amplified transmission. Furthermore, the historic absence of YF in Asia, despite abundant Ae. aegypti and an immunologically naive human population, is unexplained. We tested the hypothesis that pre-existing, heterologous flavivirus immunity, specifically from dengue (DENV) and Zika (ZIKV) viruses, limits YFV viremia and transmission by Ae. aegypti. We infected cynomolgus macaques with DENV or ZIKV, then challenged them 6–9 months later with YFV. We then measured viremia and disease and allowed Ae. aegypti mosquitoes to feed during peak macaque viremia. Although prior heterologous immunity had variable effects on disease, DENV and ZIKV immunity consistently suppressed YFV viremia. Despite no statistical difference due to a small sample size, the suppression in viremia led to a significant reduction in Ae. aegypti infection and a lack of transmission potential. These results support the hypothesis that, in DENV- and ZIKV-endemic regions such as South America and Asia, human flavivirus immunity suppresses YFV human amplification potential, reducing the risk of urban outbreaks.

Date: 2024
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DOI: 10.1038/s41467-024-54146-9

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