Cellular Immune Responses to Live Attenuated Japanese Encephalitis (JE) Vaccine SA14-14-2 in Adults in a JE/Dengue Co-Endemic Area

Turtle, Lance and Tatullo, Filippo and Bali, Tanushka and Ravi, Vasanthapuram and Soni, Mohammed and Chan, Sajesh and Chib, Savita and Venkataswamy, Manjunatha M. and Fadnis, Prachi and Yaich, Mansour and Fernandez, Stefan and Klenerman, Paul and Satchidanandam, Vijaya and Solomon, Tom (2017) Cellular Immune Responses to Live Attenuated Japanese Encephalitis (JE) Vaccine SA14-14-2 in Adults in a JE/Dengue Co-Endemic Area. In: PLOS NEGLECTED TROPICAL DISEASES, 11 (1).

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Abstract

Background Japanese encephalitis (JE) virus (JEV) causes severe epidemic encephalitis across Asia, for which the live attenuated vaccine SA14-14-2 is being used increasingly. JEV is a flavivirus, and is closely related to dengue virus (DENV), which is co-endemic in many parts of Asia, with clinically relevant interactions. There is no information on the human T cell response to SA14-14-2, or whether responses to SA14-14-2 cross-react with DENV. We used live attenuated JE vaccine SA14-14-2 as a model for studying T cell responses to JEV infection in adults, and to determine whether these T cell responses are cross-reactive with DENV, and other flaviviruses. Methods We conducted a single arm, open label clinical trial (registration: clinicaltrials.gov NCT01656200) to study T cell responses to SA14-14-2 in adults in South India, an area endemic for JE and dengue. Results Ten out of 16 (62.5%) participants seroconverted to JEV SA14-14-2, and geometric mean neutralising antibody (NAb) titre was 18.5. Proliferation responses were commonly present before vaccination in the absence of NAb, indicating a likely high degree of previous flavivirus exposure. Thirteen of 15 (87%) participants made T cell interferon-gamma (IFN gamma) responses against JEV proteins. In four subjects tested, at least some T cell epitopes mapped cross-reacted with DENV and other flaviviruses. Conclusions JEV SA14-14-2 was more immunogenic for T cell IFN gamma than for NAb in adults in this JE/DENV co-endemic area. The proliferation positive, NAb negative combination may represent a new marker of long term immunity/exposure to JE. T cell responses can cross-react between JE vaccine and DENV in a co-endemic area, illustrating a need for greater knowledge on such responses to inform the development of next-generation vaccines effective against both diseases.

Item Type:	Journal Article
Publication:	PLOS NEGLECTED TROPICAL DISEASES
Additional Information:	Copy right for this article belongs to the PUBLIC LIBRARY SCIENCE, 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
Department/Centre:	Division of Biological Sciences > Microbiology & Cell Biology
Date Deposited:	03 Apr 2017 04:50
Last Modified:	03 Apr 2017 04:50
URI:	http://eprints.iisc.ac.in/id/eprint/56457

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