Induction and maintenance of bi-functional (IFN-γ + IL-2+ and IL-2+ TNF-α+) T cell responses by DNA prime MVA boosted subtype C prophylactic vaccine tested in a Phase I trial in India.
Effective vaccine design relies on accurate knowledge of protection against a pathogen, so as to be able to induce relevant and effective protective responses against it. An ideal Human Immunodeficiency virus (HIV) vaccine should induce humoral as well as cellular immune responses to prevent initial...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2019-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0213911 |
| _version_ | 1818403782829015040 |
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| author | Sivasankaran Munusamy Ponnan Sathyamurthy Pattabiram Kannan Thiruvengadam Rajat Goyal Nikhil Singla Joyeeta Mukherjee Shweta Chatrath Philip Bergin Jakub T Kopycinski Jill Gilmour Sriram Kumar Malathy Muthu Sudha Subramaniam Soumya Swaminathan Srikanth Prasad Tripathy Hanna Elizabeth Luke |
| author_facet | Sivasankaran Munusamy Ponnan Sathyamurthy Pattabiram Kannan Thiruvengadam Rajat Goyal Nikhil Singla Joyeeta Mukherjee Shweta Chatrath Philip Bergin Jakub T Kopycinski Jill Gilmour Sriram Kumar Malathy Muthu Sudha Subramaniam Soumya Swaminathan Srikanth Prasad Tripathy Hanna Elizabeth Luke |
| author_sort | Sivasankaran Munusamy Ponnan |
| collection | DOAJ |
| description | Effective vaccine design relies on accurate knowledge of protection against a pathogen, so as to be able to induce relevant and effective protective responses against it. An ideal Human Immunodeficiency virus (HIV) vaccine should induce humoral as well as cellular immune responses to prevent initial infection of host cells or limit early events of viral dissemination. A Phase I HIV-1 prophylactic vaccine trial sponsored by the International AIDS Vaccine Initiative (IAVI) was conducted in India in 2009.The trial tested a HIV-1 subtype C vaccine in a prime-boost regimen, comprising of a DNA prime (ADVAX) and Modified Vaccine Ankara (MVA) (TBC-M4) boost. The trial reported that the vaccine regimen was safe, well tolerated, and resulted in enhancement of HIV-specific immune responses. However, preliminary immunological studies were limited to vaccine-induced IFN-γ responses against the Env and Gag peptides. The present study is a retrospective study to characterize in detail the nature of the vaccine-induced cell mediated immune responses among volunteers, using Peripheral Blood Mononuclear Cells (PBMC) that were archived during the trial. ELISpot was used to measure IFN-γ responses and polyfunctional T cells were analyzed by intracellular multicolor flow cytometry. It was observed that DNA priming and MVA boosting induced Env and Gag specific bi-functional and multi-functional CD4+ and CD8+ T cells expressing IFN-γ, TNF-α and IL-2. The heterologous prime-boost regimen appeared to be slightly superior to the homologous prime-boost regimen in inducing favorable cell mediated immune responses. These results suggest that an in-depth analysis of vaccine-induced cellular immune response can aid in the identification of correlates of an effective immunogenic response, and inform future design of HIV vaccines. |
| first_indexed | 2024-12-14T08:29:44Z |
| format | Article |
| id | doaj.art-fbdda473e15f435db4263384c2bc3a72 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-14T08:29:44Z |
| publishDate | 2019-01-01 |
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| series | PLoS ONE |
| spelling | doaj.art-fbdda473e15f435db4263384c2bc3a722022-12-21T23:09:33ZengPublic Library of Science (PLoS)PLoS ONE1932-62032019-01-01143e021391110.1371/journal.pone.0213911Induction and maintenance of bi-functional (IFN-γ + IL-2+ and IL-2+ TNF-α+) T cell responses by DNA prime MVA boosted subtype C prophylactic vaccine tested in a Phase I trial in India.Sivasankaran Munusamy PonnanSathyamurthy PattabiramKannan ThiruvengadamRajat GoyalNikhil SinglaJoyeeta MukherjeeShweta ChatrathPhilip BerginJakub T KopycinskiJill GilmourSriram KumarMalathy MuthuSudha SubramaniamSoumya SwaminathanSrikanth Prasad TripathyHanna Elizabeth LukeEffective vaccine design relies on accurate knowledge of protection against a pathogen, so as to be able to induce relevant and effective protective responses against it. An ideal Human Immunodeficiency virus (HIV) vaccine should induce humoral as well as cellular immune responses to prevent initial infection of host cells or limit early events of viral dissemination. A Phase I HIV-1 prophylactic vaccine trial sponsored by the International AIDS Vaccine Initiative (IAVI) was conducted in India in 2009.The trial tested a HIV-1 subtype C vaccine in a prime-boost regimen, comprising of a DNA prime (ADVAX) and Modified Vaccine Ankara (MVA) (TBC-M4) boost. The trial reported that the vaccine regimen was safe, well tolerated, and resulted in enhancement of HIV-specific immune responses. However, preliminary immunological studies were limited to vaccine-induced IFN-γ responses against the Env and Gag peptides. The present study is a retrospective study to characterize in detail the nature of the vaccine-induced cell mediated immune responses among volunteers, using Peripheral Blood Mononuclear Cells (PBMC) that were archived during the trial. ELISpot was used to measure IFN-γ responses and polyfunctional T cells were analyzed by intracellular multicolor flow cytometry. It was observed that DNA priming and MVA boosting induced Env and Gag specific bi-functional and multi-functional CD4+ and CD8+ T cells expressing IFN-γ, TNF-α and IL-2. The heterologous prime-boost regimen appeared to be slightly superior to the homologous prime-boost regimen in inducing favorable cell mediated immune responses. These results suggest that an in-depth analysis of vaccine-induced cellular immune response can aid in the identification of correlates of an effective immunogenic response, and inform future design of HIV vaccines.https://doi.org/10.1371/journal.pone.0213911 |
| spellingShingle | Sivasankaran Munusamy Ponnan Sathyamurthy Pattabiram Kannan Thiruvengadam Rajat Goyal Nikhil Singla Joyeeta Mukherjee Shweta Chatrath Philip Bergin Jakub T Kopycinski Jill Gilmour Sriram Kumar Malathy Muthu Sudha Subramaniam Soumya Swaminathan Srikanth Prasad Tripathy Hanna Elizabeth Luke Induction and maintenance of bi-functional (IFN-γ + IL-2+ and IL-2+ TNF-α+) T cell responses by DNA prime MVA boosted subtype C prophylactic vaccine tested in a Phase I trial in India. PLoS ONE |
| title | Induction and maintenance of bi-functional (IFN-γ + IL-2+ and IL-2+ TNF-α+) T cell responses by DNA prime MVA boosted subtype C prophylactic vaccine tested in a Phase I trial in India. |
| title_full | Induction and maintenance of bi-functional (IFN-γ + IL-2+ and IL-2+ TNF-α+) T cell responses by DNA prime MVA boosted subtype C prophylactic vaccine tested in a Phase I trial in India. |
| title_fullStr | Induction and maintenance of bi-functional (IFN-γ + IL-2+ and IL-2+ TNF-α+) T cell responses by DNA prime MVA boosted subtype C prophylactic vaccine tested in a Phase I trial in India. |
| title_full_unstemmed | Induction and maintenance of bi-functional (IFN-γ + IL-2+ and IL-2+ TNF-α+) T cell responses by DNA prime MVA boosted subtype C prophylactic vaccine tested in a Phase I trial in India. |
| title_short | Induction and maintenance of bi-functional (IFN-γ + IL-2+ and IL-2+ TNF-α+) T cell responses by DNA prime MVA boosted subtype C prophylactic vaccine tested in a Phase I trial in India. |
| title_sort | induction and maintenance of bi functional ifn γ il 2 and il 2 tnf α t cell responses by dna prime mva boosted subtype c prophylactic vaccine tested in a phase i trial in india |
| url | https://doi.org/10.1371/journal.pone.0213911 |
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