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

Turtle, LCW ORCID: 0000-0002-0778-1693, Tatullo, Filippo, Bali, Tanushka, Ravi, Vasanthapuram, Soni, Mohammed, Chan, Sajesh, Chib, Savita, Venkataswamy, Manjunatha M, Fadnis, Prachi, Yaïch, Mansour
et al (show 4 more authors) (2017) Cellular Immune Responses to Live Attenuated Japanese Encephalitis (JE) Vaccine SA14-14-2 in Adults in a JE/dengue Co- Endemic Area. PLoS Neglected Tropical Diseases, 11 (01).

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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.

Item Type: Article
Uncontrolled Keywords: T-Lymphocytes, Animals, Humans, Dengue Virus, Encephalitis Virus, Japanese, Dengue, Encephalitis, Japanese, Vaccines, Attenuated, Japanese Encephalitis Vaccines, Antibodies, Viral, Vaccination, Prospective Studies, Cross Reactions, Immunity, Cellular, Adult, India, Female, Male, Interferon-gamma, Young Adult, Antibodies, Neutralizing
Depositing User: Symplectic Admin
Date Deposited: 02 Feb 2017 10:07
Last Modified: 19 Jan 2023 07:19
DOI: 10.1371/journal.pntd.0005263
Open Access URL: http://journals.plos.org/plosntds/article?id=10.13...
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URI: https://livrepository.liverpool.ac.uk/id/eprint/3005521