Intranasal immunization with peptide-based immunogenic complex enhances BCG vaccine efficacy in a murine model of tuberculosis
Santosh Kumar, Ashima Bhaskar, Gautam Patnaik, Chetan Sharma, Dhiraj Kumar Singh, Sandeep Rai Kaushik, Shivam Chaturvedi, Gobardhan Das, Ved Prakash Dwivedi
Santosh Kumar, Ashima Bhaskar, Gautam Patnaik, Chetan Sharma, Dhiraj Kumar Singh, Sandeep Rai Kaushik, Shivam Chaturvedi, Gobardhan Das, Ved Prakash Dwivedi
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Research Article Immunology Infectious disease

Intranasal immunization with peptide-based immunogenic complex enhances BCG vaccine efficacy in a murine model of tuberculosis

Abstract

Prime-boost immunization strategies are required to control the global tuberculosis (TB) pandemic, which claims approximately 3 lives every minute. Here, we have generated an immunogenic complex against Mycobacterium tuberculosis (M.tb), consisting of promiscuous T cell epitopes (M.tb peptides) and TLR ligands assembled in liposomes. Interestingly, this complex (peptide–TLR agonist–liposomes; PTL) induced significant activation of CD4+ T cells and IFN-γ production in the PBMCs derived from PPD+ healthy individuals as compared with PPD– controls. Furthermore, intranasal delivery of PTL significantly reduced the bacterial burden in the infected mice by inducing M.tb-specific polyfunctional (IFN-γ+IL-17+TNF-α+IL-2+) immune responses and long-lasting central memory responses, thereby reducing the risk of TB recurrence in DOTS-treated infected animals. The transcriptome analysis of peptide-stimulated immune cells unveiled the molecular basis of enhanced protection. Furthermore, PTL immunization significantly boosted the Bacillus Calmette-Guerin–primed (BCG-primed) immune responses against TB. The greatly enhanced efficacy of the BCG-PTL vaccine model in controlling pulmonary TB projects PTL as an adjunct vaccine against TB.

Authors

Santosh Kumar, Ashima Bhaskar, Gautam Patnaik, Chetan Sharma, Dhiraj Kumar Singh, Sandeep Rai Kaushik, Shivam Chaturvedi, Gobardhan Das, Ved Prakash Dwivedi

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Figure 5

PTL immunization induces T cell activation in the lungs and the spleens of infected animals.

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PTL immunization induces T cell activation in the lungs and the spleens ...
T lymphocytes were isolated from the lungs of all experimental groups and stained with 7AAD, anti-CD3, anti-CD4, anti-CD8, anti-CD25, and anti-CD69 antibodies. (A) Gating strategy employed to quantify the T cell activation. (B–D) Percentage of CD4+ T cells (B) and expression of CD69 (C) and CD25 (D) on CD4+ T cells in the lungs of infected animals. (E–G) Percentage of CD8+ T cells (E) and expression of CD69 (F) and CD25 (G) on CD8+ T cells in the lungs of infected animals. (H–M) T lymphocytes were isolated from the spleens of all experimental groups and stained with 7AAD, anti-CD3, anti-CD4, anti-CD8, anti-CD25, and anti-CD69 antibodies. (H–J) Percentage of CD4+ (H), CD4+CD69+ (I), and CD4+CD25+ (J) T cells in the spleens of infected animals. (K–M) Percentage of CD8+ (K), CD8+CD69+ (L), and CD8+CD25+ (M) T cells in the spleens of infected animals. One-way ANOVA, followed by multiple Tukey tests, was performed for statistical analysis. Data are representative of 2 independent experiments (n = 5 mice/group). *P < 0.05, **P < 0.005, ***P < 0.0005.