Cellular Immune Responses to Live Attenuated Japanese Encephalitis (JE) Vaccine SA14-14-2 in Adults in a JE/Dengue Co-Endemic Area.
<h4>Background</h4>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...
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Public Library of Science (PLoS)
2017-01-01
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| Series: | PLoS Neglected Tropical Diseases |
| Online Access: | https://journals.plos.org/plosntds/article/file?id=10.1371/journal.pntd.0005263&type=printable |
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| author | Lance Turtle Filippo Tatullo Tanushka Bali Vasanthapuram Ravi Mohammed Soni Sajesh Chan Savita Chib Manjunatha M Venkataswamy Prachi Fadnis Mansour Yaïch Stefan Fernandez Paul Klenerman Vijaya Satchidanandam Tom Solomon |
| author_facet | Lance Turtle Filippo Tatullo Tanushka Bali Vasanthapuram Ravi Mohammed Soni Sajesh Chan Savita Chib Manjunatha M Venkataswamy Prachi Fadnis Mansour Yaïch Stefan Fernandez Paul Klenerman Vijaya Satchidanandam Tom Solomon |
| author_sort | Lance Turtle |
| collection | DOAJ |
| description | <h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.<h4>Trial registration</h4>clinicaltrials.gov (NCT01656200). |
| format | Article |
| id | doaj-art-3abf8932a4e44098b298ae30b439d7cb |
| institution | Kabale University |
| issn | 1935-2727 1935-2735 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Neglected Tropical Diseases |
| spelling | doaj-art-3abf8932a4e44098b298ae30b439d7cb2025-08-20T03:24:29ZengPublic Library of Science (PLoS)PLoS Neglected Tropical Diseases1935-27271935-27352017-01-01111e000526310.1371/journal.pntd.0005263Cellular Immune Responses to Live Attenuated Japanese Encephalitis (JE) Vaccine SA14-14-2 in Adults in a JE/Dengue Co-Endemic Area.Lance TurtleFilippo TatulloTanushka BaliVasanthapuram RaviMohammed SoniSajesh ChanSavita ChibManjunatha M VenkataswamyPrachi FadnisMansour YaïchStefan FernandezPaul KlenermanVijaya SatchidanandamTom Solomon<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.<h4>Trial registration</h4>clinicaltrials.gov (NCT01656200).https://journals.plos.org/plosntds/article/file?id=10.1371/journal.pntd.0005263&type=printable |
| spellingShingle | Lance Turtle Filippo Tatullo Tanushka Bali Vasanthapuram Ravi Mohammed Soni Sajesh Chan Savita Chib Manjunatha M Venkataswamy Prachi Fadnis Mansour Yaïch Stefan Fernandez Paul Klenerman Vijaya Satchidanandam Tom Solomon 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 |
| title | Cellular Immune Responses to Live Attenuated Japanese Encephalitis (JE) Vaccine SA14-14-2 in Adults in a JE/Dengue Co-Endemic Area. |
| title_full | Cellular Immune Responses to Live Attenuated Japanese Encephalitis (JE) Vaccine SA14-14-2 in Adults in a JE/Dengue Co-Endemic Area. |
| title_fullStr | Cellular Immune Responses to Live Attenuated Japanese Encephalitis (JE) Vaccine SA14-14-2 in Adults in a JE/Dengue Co-Endemic Area. |
| title_full_unstemmed | Cellular Immune Responses to Live Attenuated Japanese Encephalitis (JE) Vaccine SA14-14-2 in Adults in a JE/Dengue Co-Endemic Area. |
| title_short | Cellular Immune Responses to Live Attenuated Japanese Encephalitis (JE) Vaccine SA14-14-2 in Adults in a JE/Dengue Co-Endemic Area. |
| title_sort | cellular immune responses to live attenuated japanese encephalitis je vaccine sa14 14 2 in adults in a je dengue co endemic area |
| url | https://journals.plos.org/plosntds/article/file?id=10.1371/journal.pntd.0005263&type=printable |
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