Cellular T-cell immune response profiling by tetravalent dengue subunit vaccine (DSV4) candidate in mice
While most vaccines aim to develop a solid humoral and neutralizing antibody response against the pathogen, an effective vaccine candidate should be able to stimulate both the B-cell mediated humoral immunity, and T-cell mediated cellular immunity. The focus of vaccinology is rapidly gaining to gene...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1128784/full |
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| author | Charu Aggarwal Viswanathan Ramasamy Amit Garg Rahul Shukla Rahul Shukla Navin Khanna Navin Khanna |
| author_facet | Charu Aggarwal Viswanathan Ramasamy Amit Garg Rahul Shukla Rahul Shukla Navin Khanna Navin Khanna |
| author_sort | Charu Aggarwal |
| collection | DOAJ |
| description | While most vaccines aim to develop a solid humoral and neutralizing antibody response against the pathogen, an effective vaccine candidate should be able to stimulate both the B-cell mediated humoral immunity, and T-cell mediated cellular immunity. The focus of vaccinology is rapidly gaining to generate T cell responses, which can mediate pathogen clearance and help B cells leading to protective antibody responses. Here we evaluate the cellular immune response of the pre-clinical tetravalent dengue subunit vaccine candidate, DSV4, in mice. While we have shown previously that DSV4 induces type-specific neutralizing antibody responses in mice, in this study, we show that the vaccine candidate DSV4 well induces dengue-specific T- cell responses evaluated by their ability to produce IFN-γ. In addition to IFN-γ secretion by both CD4+ and CD8+ T-cells in immunized mice, we observed that DSV4 also induces a higher frequency and cytokine functions of follicular CD4+ helper T-cells (TFH). These cytokines lead to an efficient germinal center reaction and potent B cell antibody response. Apart from TFH response, DSV4 stimulated Type 1 T helper cells (TH1) which is characteristic of a viral infection leading to secretion of pro-inflammatory cytokines and phagocyte-dependent protective immune responses. Our study highlights that DSV4 can mediate both arms of adaptive immunity-humoral and cell-mediated immunity in mice. By elucidating vaccine-specific T cell response, our work has implications in showing DSV4 as an effective, type-specific and safe dengue vaccine candidate. |
| first_indexed | 2024-04-10T06:58:17Z |
| format | Article |
| id | doaj.art-7e2be23384484aa6baf268f7c6432947 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-10T06:58:17Z |
| publishDate | 2023-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-7e2be23384484aa6baf268f7c64329472023-02-28T05:17:31ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-02-011410.3389/fimmu.2023.11287841128784Cellular T-cell immune response profiling by tetravalent dengue subunit vaccine (DSV4) candidate in miceCharu Aggarwal0Viswanathan Ramasamy1Amit Garg2Rahul Shukla3Rahul Shukla4Navin Khanna5Navin Khanna6Translational Health, Molecular Medicine Division, International Centre for Genetic Engineering and Biotechnology, New Delhi, IndiaTranslational Health, Molecular Medicine Division, International Centre for Genetic Engineering and Biotechnology, New Delhi, IndiaTranslational Health, Molecular Medicine Division, International Centre for Genetic Engineering and Biotechnology, New Delhi, IndiaTranslational Health, Molecular Medicine Division, International Centre for Genetic Engineering and Biotechnology, New Delhi, IndiaDivision of Virus Research and Therapeutics, CSIR-Central Drug Research Institute, Lucknow, IndiaTranslational Health, Molecular Medicine Division, International Centre for Genetic Engineering and Biotechnology, New Delhi, IndiaTranslational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad, IndiaWhile most vaccines aim to develop a solid humoral and neutralizing antibody response against the pathogen, an effective vaccine candidate should be able to stimulate both the B-cell mediated humoral immunity, and T-cell mediated cellular immunity. The focus of vaccinology is rapidly gaining to generate T cell responses, which can mediate pathogen clearance and help B cells leading to protective antibody responses. Here we evaluate the cellular immune response of the pre-clinical tetravalent dengue subunit vaccine candidate, DSV4, in mice. While we have shown previously that DSV4 induces type-specific neutralizing antibody responses in mice, in this study, we show that the vaccine candidate DSV4 well induces dengue-specific T- cell responses evaluated by their ability to produce IFN-γ. In addition to IFN-γ secretion by both CD4+ and CD8+ T-cells in immunized mice, we observed that DSV4 also induces a higher frequency and cytokine functions of follicular CD4+ helper T-cells (TFH). These cytokines lead to an efficient germinal center reaction and potent B cell antibody response. Apart from TFH response, DSV4 stimulated Type 1 T helper cells (TH1) which is characteristic of a viral infection leading to secretion of pro-inflammatory cytokines and phagocyte-dependent protective immune responses. Our study highlights that DSV4 can mediate both arms of adaptive immunity-humoral and cell-mediated immunity in mice. By elucidating vaccine-specific T cell response, our work has implications in showing DSV4 as an effective, type-specific and safe dengue vaccine candidate.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1128784/fulldengue vaccineDSV4BALB/ctype-specific immunityADET-cell |
| spellingShingle | Charu Aggarwal Viswanathan Ramasamy Amit Garg Rahul Shukla Rahul Shukla Navin Khanna Navin Khanna Cellular T-cell immune response profiling by tetravalent dengue subunit vaccine (DSV4) candidate in mice Frontiers in Immunology dengue vaccine DSV4 BALB/c type-specific immunity ADE T-cell |
| title | Cellular T-cell immune response profiling by tetravalent dengue subunit vaccine (DSV4) candidate in mice |
| title_full | Cellular T-cell immune response profiling by tetravalent dengue subunit vaccine (DSV4) candidate in mice |
| title_fullStr | Cellular T-cell immune response profiling by tetravalent dengue subunit vaccine (DSV4) candidate in mice |
| title_full_unstemmed | Cellular T-cell immune response profiling by tetravalent dengue subunit vaccine (DSV4) candidate in mice |
| title_short | Cellular T-cell immune response profiling by tetravalent dengue subunit vaccine (DSV4) candidate in mice |
| title_sort | cellular t cell immune response profiling by tetravalent dengue subunit vaccine dsv4 candidate in mice |
| topic | dengue vaccine DSV4 BALB/c type-specific immunity ADE T-cell |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1128784/full |
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