TY - JOUR
T1 - Potential role of heterologous flavivirus immunity in preventing urban transmission of yellow fever virus
AU - Shinde, Divya P.
AU - Plante, Jessica
AU - Scharton, Dionna
AU - Mitchell, Brooke
AU - Walker, Jordyn
AU - Azar, Sasha
AU - Kroon Campos, Rafael
AU - Sacchetto, Lívia
AU - Drumond, Betânia P.
AU - Vasilakis, Nikos
AU - Plante, Kenneth S.
AU - Weaver, Scott
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/12
Y1 - 2024/12
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-024-54146-9
DO - 10.1038/s41467-024-54146-9
M3 - Article
C2 - 39523371
AN - SCOPUS:85209479794
SN - 2041-1723
VL - 15
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 9728
ER -