Magelda MontoyaMatthew CollinsWanwisa DejnirattisaiLeah C. KatzelnickHenry Puerta-GuardoRamesh JadiSamuel SchildhauerPiyada SupasaSirijitt VasanawathanaPrida MalasitJuthathip MongkolsapayaAruna D. De SilvaHasitha TisseraAngel BalmasedaGavin ScreatonAravinda M. De SilvaEva HarrisMinistry of Health ColomboUniversity of Colombo Faculty of MedicineUniversity of OxfordUniversity of California, BerkeleyUniversity of North Carolina School of MedicineImperial College LondonKhon Kaen Regional HospitalThailand National Center for Genetic Engineering and BiotechnologyFaculty of Medicine, Siriraj Hospital, Mahidol UniversityGenetech Research InstituteMinistry of Health2019-08-282019-08-282018-07-13Journal of Infectious Diseases. Vol.218, No.4 (2018), 536-54515376613002218992-s2.0-85049929472https://repository.li.mahidol.ac.th/handle/20.500.14594/46509© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. Background The 4 dengue virus serotypes (DENV1-4) and Zika virus (ZIKV) are related mosquito-borne flaviviruses of major importance globally. While monoclonal antibodies and plasma from DENV-immune donors can neutralize or enhance ZIKV in vitro and in small-animal models, and vice versa, the extent, duration, and significance of cross-reactivity in humans remains unknown, particularly in flavivirus-endemic regions. Methods We studied neutralizing antibodies to ZIKV and DENV1-4 in longitudinal serologic specimens collected through 3 years after infection from people in Latin America and Asia with laboratory-confirmed DENV infections. We also evaluated neutralizing antibodies to ZIKV and DENV1-4 in patients with Zika through 6 months after infection. Results In patients with Zika, the highest neutralizing antibody titers were to ZIKV, with low-level cross-reactivity to DENV1-4 that was greater in DENV-immune individuals. We found that, in primary and secondary DENV infections, neutralizing antibody titers to ZIKV were markedly lower than to the infecting DENV and heterologous DENV serotypes. Cross-neutralization was greatest in early convalescence, then ZIKV neutralization decreased, remaining at low levels over time. Conclusions Patterns of antibody cross-neutralization suggest that ZIKV lies outside the DENV serocomplex. Neutralizing antibody titers can distinguish ZIKV from DENV infections when all viruses are analyzed simultaneously. These findings have implications for understanding natural immunity and vaccines.Mahidol UniversityMedicineArticleSCOPUS10.1093/infdis/jiy164