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

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 (ifnγ) 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 ifnγ 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. trial registration: clinicaltrials.gov (nct01656200) © 2017 public library of science. all rights reserved.