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Title: Original antigenic sin in Japanese encephalitis vaccination
Author: Tatullo, Filippo
ISNI:       0000 0004 9359 218X
Awarding Body: University of Liverpool
Current Institution: University of Liverpool
Date of Award: 2020
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Japanese encephalitis (JE) virus (JEV) is the main cause of viral encephalitis in South and South-East Asia. JEV is a member of the flavivirus Genus (Family Flaviviridae) and it is transmitted by mosquitoes. A live attenuated vaccine is used in many endemic countries. Dengue virus (DENV) is another flavivirus, closely related to JEV, also transmitted by mosquitoes, which is endemic in all tropical and subtropical countries, including India. This study aimed to analyse the antibody and T cell responses to the live attenuated JE vaccine (LAJV) and their cross-reactivity with the 4 DENV serotypes in adult Indians. Participants were vaccinated with the LAJV and peripheral blood mononuclear cell and serum samples were collected before and after vaccination. Antibody responses specific to JEV and DENV were studied by plaque reduction neutralisation test and ELISA whereas T cell responses were measured by interferon ? - ELISpot and intracellular cytokine staining. Neutralising antibody (NAb) response to the LAJV was observed in 3 out of 16 volunteers (18.75%) with a peak reciprocal geometric mean titre of 20 at 4 weeks after vaccination. Ten volunteers (62.5%) were DENV exposed at baseline, as assessed by IgG ELISA. Interestingly, original antigenic sin (OAS) was observed in approximately 30% of DENV exposed individuals, as shown by the fact that they mounted a NAb response to DENV rather than JEV following vaccination. OAS was observed in responders as well as non responders. In addition, data suggested DENV NAb at baseline could increase immunogenicity of the vaccine. Previous work performed by others on this cohort showed that T cell responses, which peaked at 2 weeks following vaccination, were identified in most volunteers by ELISpot. Furthermore, T cell responses specific to JEV were detected following vaccination even in volunteers without antibody response. Five T cell epitopes were identified after vaccination and 4 of them showed cross-reactivity with one or more DENV variants. Three of them were also detected before vaccination. T cell data indicated that the vaccine was able to induce de novo DENV cross-reactive as well as JEV specific T cell responses. Finally, previous cross-reactive DENV responses did not inhibit de novo T cell responses.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral