A lipidated bi-epitope vaccine comprising of MHC-I and MHC-II binder peptides elicits protective CD4 T cell and CD8 T cell immunity against Mycobacterium tuberculosis
Abstract Background The clinical trials conducted at Chingleput India suggest that BCG fails to protect against tuberculosis (TB) in TB-endemic population. Recent studies advocate that non-tuberculous mycobacteria and latent Mycobacterium tuberculosis (Mtb) infection interferes in the antigen proces...
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| Format: | Article |
| Language: | English |
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BMC
2018-10-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12967-018-1653-x |
| _version_ | 1819017035407949824 |
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| author | Pradeep K. Rai Sathi Babu Chodisetti Sudeep K. Maurya Sajid Nadeem Weiguang Zeng Ashok K. Janmeja David C. Jackson Javed N. Agrewala |
| author_facet | Pradeep K. Rai Sathi Babu Chodisetti Sudeep K. Maurya Sajid Nadeem Weiguang Zeng Ashok K. Janmeja David C. Jackson Javed N. Agrewala |
| author_sort | Pradeep K. Rai |
| collection | DOAJ |
| description | Abstract Background The clinical trials conducted at Chingleput India suggest that BCG fails to protect against tuberculosis (TB) in TB-endemic population. Recent studies advocate that non-tuberculous mycobacteria and latent Mycobacterium tuberculosis (Mtb) infection interferes in the antigen processing and presentation of BCG in inducing protective immunity against Mtb. Thereby, indicating that any vaccine that require extensive antigen processing may not be efficacious in TB-endemic zones. Recently, we have demonstrated that the vaccine candidate L91, which is composed of lipidated promiscuous MHC-II binder epitope, derived from latency associated Acr1 antigen of Mtb is immunogenic in the murine and Guinea pig models of TB and conferred better protection than BCG against Mtb. Methods In this study, we have used a multi-stage based bi-epitope vaccine, namely L4.8, comprising of MHC-I and MHC-II binding peptides of active (TB10.4) and latent (Acr1) stages of Mtb antigens, respectively. These peptides were conjugated to the TLR-2 agonist Pam2Cys. Results L4.8 significantly elicited both CD8 T cells and CD4 T cells immunity, as evidenced by increase in the enduring polyfunctional CD8 T cells and CD4 T cells. L4.8 efficiently declined Mtb-burden and protected animals better than BCG and L91, even at the late stage of Mtb infection. Conclusions The BCG-L4.8 prime boost strategy imparts a better protection against TB than the BCG alone. This study emphatically denotes that L4.8 can be a promising future vaccine candidate for controlling active and latent TB. |
| first_indexed | 2024-12-21T02:57:07Z |
| format | Article |
| id | doaj.art-657a45b5c2694d859269eae6c3f5c7f6 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-12-21T02:57:07Z |
| publishDate | 2018-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-657a45b5c2694d859269eae6c3f5c7f62022-12-21T19:18:17ZengBMCJournal of Translational Medicine1479-58762018-10-0116111210.1186/s12967-018-1653-xA lipidated bi-epitope vaccine comprising of MHC-I and MHC-II binder peptides elicits protective CD4 T cell and CD8 T cell immunity against Mycobacterium tuberculosisPradeep K. Rai0Sathi Babu Chodisetti1Sudeep K. Maurya2Sajid Nadeem3Weiguang Zeng4Ashok K. Janmeja5David C. Jackson6Javed N. Agrewala7CSIR-Institute of Microbial TechnologyCSIR-Institute of Microbial TechnologyCSIR-Institute of Microbial TechnologyCSIR-Institute of Microbial TechnologyDepartment of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of MelbourneDepartment of Pulmonary Medicine, Government Medical College and HospitalDepartment of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of MelbourneCSIR-Institute of Microbial TechnologyAbstract Background The clinical trials conducted at Chingleput India suggest that BCG fails to protect against tuberculosis (TB) in TB-endemic population. Recent studies advocate that non-tuberculous mycobacteria and latent Mycobacterium tuberculosis (Mtb) infection interferes in the antigen processing and presentation of BCG in inducing protective immunity against Mtb. Thereby, indicating that any vaccine that require extensive antigen processing may not be efficacious in TB-endemic zones. Recently, we have demonstrated that the vaccine candidate L91, which is composed of lipidated promiscuous MHC-II binder epitope, derived from latency associated Acr1 antigen of Mtb is immunogenic in the murine and Guinea pig models of TB and conferred better protection than BCG against Mtb. Methods In this study, we have used a multi-stage based bi-epitope vaccine, namely L4.8, comprising of MHC-I and MHC-II binding peptides of active (TB10.4) and latent (Acr1) stages of Mtb antigens, respectively. These peptides were conjugated to the TLR-2 agonist Pam2Cys. Results L4.8 significantly elicited both CD8 T cells and CD4 T cells immunity, as evidenced by increase in the enduring polyfunctional CD8 T cells and CD4 T cells. L4.8 efficiently declined Mtb-burden and protected animals better than BCG and L91, even at the late stage of Mtb infection. Conclusions The BCG-L4.8 prime boost strategy imparts a better protection against TB than the BCG alone. This study emphatically denotes that L4.8 can be a promising future vaccine candidate for controlling active and latent TB.http://link.springer.com/article/10.1186/s12967-018-1653-xMultistage vaccinePromiscuous peptideTLR-2TBMtbTh1 cells |
| spellingShingle | Pradeep K. Rai Sathi Babu Chodisetti Sudeep K. Maurya Sajid Nadeem Weiguang Zeng Ashok K. Janmeja David C. Jackson Javed N. Agrewala A lipidated bi-epitope vaccine comprising of MHC-I and MHC-II binder peptides elicits protective CD4 T cell and CD8 T cell immunity against Mycobacterium tuberculosis Journal of Translational Medicine Multistage vaccine Promiscuous peptide TLR-2 TB Mtb Th1 cells |
| title | A lipidated bi-epitope vaccine comprising of MHC-I and MHC-II binder peptides elicits protective CD4 T cell and CD8 T cell immunity against Mycobacterium tuberculosis |
| title_full | A lipidated bi-epitope vaccine comprising of MHC-I and MHC-II binder peptides elicits protective CD4 T cell and CD8 T cell immunity against Mycobacterium tuberculosis |
| title_fullStr | A lipidated bi-epitope vaccine comprising of MHC-I and MHC-II binder peptides elicits protective CD4 T cell and CD8 T cell immunity against Mycobacterium tuberculosis |
| title_full_unstemmed | A lipidated bi-epitope vaccine comprising of MHC-I and MHC-II binder peptides elicits protective CD4 T cell and CD8 T cell immunity against Mycobacterium tuberculosis |
| title_short | A lipidated bi-epitope vaccine comprising of MHC-I and MHC-II binder peptides elicits protective CD4 T cell and CD8 T cell immunity against Mycobacterium tuberculosis |
| title_sort | lipidated bi epitope vaccine comprising of mhc i and mhc ii binder peptides elicits protective cd4 t cell and cd8 t cell immunity against mycobacterium tuberculosis |
| topic | Multistage vaccine Promiscuous peptide TLR-2 TB Mtb Th1 cells |
| url | http://link.springer.com/article/10.1186/s12967-018-1653-x |
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