Antibody cross-reactivity and evidence of susceptibility to emerging Flaviviruses in the dengue-endemic Brazilian Amazon
Salgado, B. B.; Maues, F. C. d. J.; Jordao, M. F.; Pereira, R. L.; Teixeira, D. A. T.; Parise, P. L.; Granja, F.; Souza, H. F. S.; Yamamoto, M. M.; Chiang, J. O.; Martins, L. C.; Boscardin, S. B.; Lalwani, J. D. B.; Vasconcelos, P. F. C.; Modena, J. L. P.; Lalwani, P. J.
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Flaviviruses are vector-borne positive sense RNA viruses with enormous potential to cause a spectrum of severe diseases in naive populations and long-term public health impact. Several of these Flavivirus es can co-circulate; recently, Zika virus (ZIKV) is becoming increasingly prevalent in Dengue virus (DENV) endemic regions. Pre-existing immunity to one virus can modulate the response to a heterologous virus; however, the serological cross-reaction between these emerging viruses in DENV endemic region are poorly understood. In this study, we estimated the seropositivity rates of nine different Flavivirus es among residents of Manaus city in Brazil. Next, we assessed antibody cross-reactivity of DENV-positive individuals with ZIKV using hemagglutination inhibition assay (HIA), purified envelope proteins in an ELISA, and live virus neutralization test. 74.52% of participants were IgG positive (310/416) as estimated by lateral flow tests. Overall, 93.7% of participants were seropositive (419/447) for at least one DENV serotype and the DENV seropositivity ranged between 84.8% and 91.0% as determined by HIA. DENV positive individuals with high antibody titers in HIA or envelope protein domain III (EDIII)-ELISA reacted strongly with ZIKV, whereas individuals with low anti-DENV antibody titers reacted poorly towards ZIKV. Live virus neutralization test with ZIKV confirmed that dengue serogroup and ZIKV-spondweni serogroup are distant and DENV-positive individuals do not cross-neutralize ZIKV efficiently. Taken together, we observed a high prevalence of DENV in the Manaus-Amazon region and a varying degree of serological reactivity against emerging viruses. Ecological and epidemiological conditions in Manaus makes its population susceptible for further arbovirus outbreaks; hence functional vector control program and febrile-syndrome surveillance are essential to identify unforeseen epidemiological threats.
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