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Identification of Immune Responses to Japanese Encephalitis Virus Specific T Cell Epitopes.

ABSTRACT: Background: Due to the similarity between the dengue (DENV) and the Japanese encephalitis virus (JEV) there is potential for immune cross-reaction. We sought to identify T cell epitopes that are specific to JEV and do not cross react with DENV. Methodology: 20mer peptides were synthesized from regions which showed >90% conservation. Using IFN? cultured ELISpot assays, we investigated JEV-specific T cell responses in DENV^- and JEV^- non-immune individuals (DENV^-JEV^- = 21), JEV seronegative and had not received the JE vaccine, but who were DENV seropositive (DENV⁺JEV^- = 22), JEV⁺(seropositive for JEV and had received the JE vaccine), but seronegative for DENV (DENV^-JEV⁺ = 23). We further assessed the responses to these peptides by undertaking ex vivo IFN? assays and flow cytometry. Results: None of DENV^-JEV^- individuals responded to any of the 20 JEV-specific peptides. High frequency of responses was seen to 6/20 peptides by individuals who were JEV⁺ but DENV^-, where over 75% of the individuals responded to at least one peptide. P34 was the most immunogenic peptide, recognized by 20/23 (86.9%) individuals who were DENV^-JEV⁺, followed by peptide 3 and peptide 7 recognized by 19/23 (82.6%). Peptide 34 from the NS2a region, showed <25% homology with any flaviviruses, and <20% homology with any DENV serotype. Peptide 20 and 32, which were also from the non-structural protein regions, showed <25% homology with DENV. Ex vivo responses to these peptides were less frequent, with only 40% of individuals responding to peptide 34 and 16-28% to other peptides, probably as 5/6 peptides were recognized by CD4+ T cells. Discussion: We identified six highly conserved, T cell epitopes which are highly specific for JEV, in the Sri Lankan population. Since both JEV and DENV co-circulate in the same regions and since both JE and dengue vaccines are likely to be co-administered in the same geographical regions in future, these JEV-specific T cell epitopes would be useful to study JEV-specific T cell responses, in order to further understand how DENV and JEV-specific cellular immune responses influence each other.

SUBMITTER: Pushpakumara PD

PROVIDER: S-EPMC7029616 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Identification of Immune Responses to Japanese Encephalitis Virus Specific T Cell Epitopes.

Pushpakumara Pradeep Darshana PD Jeewandara Chandima C Wijesinghe Ayesha A Gomes Laksiri L Ogg Graham S GS Goonasekara Charitha Lakshini CL Malavige Gathsaurie Neelika GN

Frontiers in public health 20200212

Background: Due to the similarity between the dengue (DENV) and the Japanese encephalitis virus (JEV) there is potential for immune cross-reaction. We sought to identify T cell epitopes that are specific to JEV and do not cross react with DENV. Methodology: 20mer peptides were synthesized from regions which showed >90% conservation. Using IFNγ cultured ELISpot assays, we investigated JEV-specific T cell responses in DENV- and JEV- non-immune individuals (DENV< ...[more]

PMID: 32117854

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Project description:INTRODUCTION:Although immune responses to the Japanese Encephalitis virus (JEV), and the dengue viruses (DENV) have a potential to modulate the immune responses to each other, this has been poorly investigated. Therefore, we developed an ELISA to identify JEV specific, DENV non cross-reactive antibody responses by identifying JEV specific, highly conserved regions of the virus and proceeded to investigate if the presence of JEV specific antibodies associate with dengue disease severity. METHODOLOGY AND RESULTS:22 JEV specific peptides were identified from highly conserved regions of the virus and the immunogenicity and specificity of these peptides were assessed in individuals who were non-immune to JEV and DENV (JEV-DENV-, N = 30), those who were only immune to the JEV and not DENV (JEV+DENV-, N = 30), those who were only immune to DENV(JEV-DENV+, N = 30) and in those who were immune to both viruses (JEV+DENV+, N = 30). 7/22 peptides were found to be highly immunogenic and specific and these 7 peptides were used as a pool to further evaluate JEV-specific responses. All 30/30 JEV+DENV- and 30/30 JEV+DENV+ individuals, and only 3/30 (10%) JEV-DENV+ individuals responded to this pool. We further evaluated this pool of 7 peptides in patients following primary and secondary dengue infection during the convalescent period and found that the JEV-specific peptides, were unlikely to cross react with DENV IgG antibodies. We further compared this in-house ELISA developed with the peptide pool with an existing commercial JEV IgG assay to identify JEV-specific IgG following vaccination, and our in-house ELISA was found to be more sensitive. We then proceeded to investigate if the presence of JEV-specific antibodies were associated with dengue disease severity, and we found that those who had past severe dengue (n = 175) were significantly more likely (p<0.0001) to have JEV-specific antibodies than those with past non-severe dengue (n = 175) (OR 5.3, 95% CI 3.3 to 8.3). CONCLUSIONS:As our data show that this assay is highly sensitive and specific for detection of JEV-specific antibody responses, it would be an important tool to determine how JEV seropositivity modulate dengue immunity and disease severity when undertaking dengue vaccine trials.

Dataset Information

Identification of Immune Responses to Japanese Encephalitis Virus Specific T Cell Epitopes.

Publications

Identification of Immune Responses to Japanese Encephalitis Virus Specific T Cell Epitopes.

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