@article{30464165b87b4e5892d094afc82d2051,
title = "Pre-existing Immunity to Japanese Encephalitis Virus Alters CD4 T Cell Responses to Zika Virus Inactivated Vaccine",
abstract = "The epidemic spread of Zika virus (ZIKV), associated with devastating neurologic syndromes, has driven the development of multiple ZIKV vaccines candidates. An effective vaccine should induce ZIKV-specific T cell responses, which are shown to improve the establishment of humoral immunity and contribute to viral clearance. Here we investigated how previous immunization against Japanese encephalitis virus (JEV) and yellow fever virus (YFV) influences T cell responses elicited by a Zika purified-inactivated virus (ZPIV) vaccine. We demonstrate that three doses of ZPIV vaccine elicited robust CD4 T cell responses to ZIKV structural proteins, while ZIKV-specific CD4 T cells in pre-immunized individuals with JEV vaccine, but not YFV vaccine, were more durable and directed predominantly toward conserved epitopes, which elicited Th1 and Th2 cytokine production. In addition, T cell receptor repertoire analysis revealed preferential expansion of cross-reactive clonotypes between JEV and ZIKV, suggesting that pre-existing immunity against JEV may prime the establishment of stronger CD4 T cell responses to ZPIV vaccination. These CD4 T cell responses correlated with titers of ZIKV-neutralizing antibodies in the JEV pre-vaccinated group, but not in flavivirus-na{\"i}ve or YFV pre-vaccinated individuals, suggesting a stronger contribution of CD4 T cells in the generation of neutralizing antibodies in the context of JEV-ZIKV cross-reactivity.",
keywords = "CD4 T cell, TCR repertoire, cross-reactivity, flavivirus, vaccine, zika virus",
author = "Lima, {Noemia S.} and Damee Moon and Samuel Darko and {De La Barrera}, {Rafael A.} and Leyi Lin and Koren, {Michael A.} and Jarman, {Richard G.} and Eckels, {Kenneth H.} and Thomas, {Stephen J.} and Michael, {Nelson L.} and Kayvon Modjarrad and Douek, {Daniel C.} and Lydie Trautmann",
note = "Funding Information: The authors would like to thank the study participants of the clinical trial; the members of Lydie Trautmann's lab; the members of the Vaccine Research Center sequencing core: Amy Ransier, Kiera Coy, and Farida Laboune; the Military HIV Research Program flow core; the Vaccine Research Center flow core, particularly David Ambrozak; members of the Walter Reed Army Institute of Research Emerging Infectious Diseases Branch, Viral Diseases Branch, Pilot Bioproduction Facility and Clinical Trials Center as well as all the volunteer participants of the Phase 1 clinical trial who contributed the biologic specimens for this study. The Phase 1 clinical trial was carried out by a Research Collaborative Agreement between WRAIR, NIAID, and BARDA (NIH # Y1-A1-5026-03; USAMRMC # MRMC 15-0001). Funding. This study was funded in part by the Intramural Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. This work was supported by a cooperative agreement (W81XWH-07-2-0067) between the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. and the U.S. Department of Defense (DoD). The U.S. Army Medical Research Acquisition Activity (820 Chandler Street, Fort Detrick, MD 21702-5014, USA) is the awarding and administering acquisition office for the cooperative agreement. The work was also funded by the US Defense Health Agency (0130602D16). The content of this publication does not necessarily reflect the views or policies of the Department of the Army or Department of Defense. Publisher Copyright: {\textcopyright} Copyright {\textcopyright} 2021 Lima, Moon, Darko, De La Barrera, Lin, Koren, Jarman, Eckels, Thomas, Michael, Modjarrad, Douek and Trautmann.",
year = "2021",
month = feb,
day = "24",
doi = "10.3389/fimmu.2021.640190",
language = "English (US)",
volume = "12",
journal = "Frontiers in Immunology",
issn = "1664-3224",
publisher = "Frontiers Media S. A.",
}