title: Cellular Immune Responses to Live Attenuated Japanese Encephalitis (JE) Vaccine SA14-14-2 in Adults in a JE/Dengue Co-Endemic Area.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  clinicaltrials.gov (NCT01656200).
authors.affiliation: Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom.|NIHR Health Protection Research Unit for Emerging and Zoonotic Infections, University of Liverpool, Liverpool, United Kingdom.|Tropical & Infectious Disease Unit, Royal Liverpool University Hospital, Liverpool, United Kingdom.
authors.forename: Lance
authors.identifier: 0000-0002-0778-1693
authors.initials: L
authors.lastname: Turtle
authors.affiliation: Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom.|Dept of Neurovirology, National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, India.
authors.forename: Filippo
authors.initials: F
authors.lastname: Tatullo
authors.affiliation: Dept of Microbiology and Cell Biology, Indian Institute of Science, Bengaluru, India.
authors.forename: Tanushka
authors.initials: T
authors.lastname: Bali
authors.affiliation: Dept of Neurovirology, National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, India.
authors.forename: Vasanthapuram
authors.initials: V
authors.lastname: Ravi
authors.affiliation: Dept of Microbiology and Cell Biology, Indian Institute of Science, Bengaluru, India.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Soni
authors.affiliation: Dept of Microbiology and Cell Biology, Indian Institute of Science, Bengaluru, India.
authors.forename: Sajesh
authors.initials: S
authors.lastname: Chan
authors.affiliation: Dept of Microbiology and Cell Biology, Indian Institute of Science, Bengaluru, India.
authors.forename: Savita
authors.initials: S
authors.lastname: Chib
authors.affiliation: Dept of Neurovirology, National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, India.
authors.forename: Manjunatha M
authors.initials: MM
authors.lastname: Venkataswamy
authors.affiliation: Dept of Neurovirology, National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, India.
authors.forename: Prachi
authors.initials: P
authors.lastname: Fadnis
authors.affiliation: Vaxyn Consulting, Paris, Île-de-France, France.
authors.forename: Mansour
authors.initials: M
authors.lastname: Yaïch
authors.affiliation: Dept of Virology, Armed Forces Research Institute of Medical Science (AFRIMS), Bangkok, Thailand.
authors.forename: Stefan
authors.initials: S
authors.lastname: Fernandez
authors.affiliation: Translational Gastroenterology Unit, Nuffield Dept. of Medicine, University of Oxford, Peter Medawar Building for Pathogen Research, Oxford, United Kingdom.
authors.forename: Paul
authors.initials: P
authors.lastname: Klenerman
authors.affiliation: Dept of Microbiology and Cell Biology, Indian Institute of Science, Bengaluru, India.
authors.forename: Vijaya
authors.initials: V
authors.lastname: Satchidanandam
authors.affiliation: Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom.|NIHR Health Protection Research Unit for Emerging and Zoonotic Infections, University of Liverpool, Liverpool, United Kingdom.|Walton Centre NHS Foundation Trust, Liverpool, United Kingdom.
authors.forename: Tom
authors.initials: T
authors.lastname: Solomon
mesh_terms: D000328:Adult; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D003429:Cross Reactions; D003715:Dengue / Q000453:epidemiology; D003716:Dengue Virus / Q000235:genetics; D004664:Encephalitis Virus, Japanese / Q000276:immunology; D004672:Encephalitis, Japanese / Q000453:epidemiology / Q000517:prevention & control*; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D007194:India / Q000453:epidemiology; D007371:Interferon-gamma / Q000097:blood; D022321:Japanese Encephalitis Vaccines / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D011446:Prospective Studies; D013601:T-Lymphocytes / Q000276:immunology*; D014611:Vaccination / Q000379:methods; D014613:Vaccines, Attenuated / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D022321:Japanese Encephalitis Vaccines; D014613:Vaccines, Attenuated; D007371:Interferon-gamma