Intranasal Immunization with Peptide-based Immunogenic Complex Enhances BCG Vaccine Efficacy in murine model of Tuberculosis

Santosh Kumar; Ashima Bhaskar; Gautam Patnaik; Chetan Sharma; Dhiraj K. Singh; Sandeep Kaushik; Shivam Chaturvedi; Gobardhan Das; Ved Prakash Dwivedi

doi:10.1172/jci.insight.145228

Intranasal Immunization with Peptide-based Immunogenic Complex Enhances BCG Vaccine Efficacy in murine model of Tuberculosis

Santosh Kumar,¹ Ashima Bhaskar,² Gautam Patnaik,³ Chetan Sharma,⁴ Dhiraj K. Singh,⁵ Sandeep Kaushik,⁶ Shivam Chaturvedi,¹ Gobardhan Das,⁷ and Ved Prakash Dwivedi¹

Published January 14, 2021 - More info

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Abstract

Novel 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 (PTLs; peptide-TLR agonist-liposomes) induced significant activation of CD4⁺ T cells and IFNγ production in the PBMCs derived from PPD⁺ healthy individuals as compared to PPD^- controls. Furthermore, intranasal delivery of PTLs significantly reduced the bacterial burden in the infected mice by inducing M.tb specific polyfunctional (IFNγ⁺IL17⁺TNFα⁺IL2⁺) 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, PTLs immunization significantly boosted the BCG-primed immune responses against TB. The greatly enhanced efficacy of BCG-PTLs vaccine model in controlling pulmonary TB projects PTLs as an adjunct vaccine against TB.

Intranasal Immunization with Peptide-based Immunogenic Complex Enhances BCG Vaccine Efficacy in murine model of Tuberculosis

Santosh Kumar,¹ Ashima Bhaskar,² Gautam Patnaik,³ Chetan Sharma,⁴ Dhiraj K. Singh,⁵ Sandeep Kaushik,⁶ Shivam Chaturvedi,¹ Gobardhan Das,⁷ and Ved Prakash Dwivedi¹

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Intranasal Immunization with Peptide-based Immunogenic Complex Enhances BCG Vaccine Efficacy in murine model of Tuberculosis

Santosh Kumar,1 Ashima Bhaskar,2 Gautam Patnaik,3 Chetan Sharma,4 Dhiraj K. Singh,5 Sandeep Kaushik,6 Shivam Chaturvedi,1 Gobardhan Das,7 and Ved Prakash Dwivedi1

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Santosh Kumar,¹ Ashima Bhaskar,² Gautam Patnaik,³ Chetan Sharma,⁴ Dhiraj K. Singh,⁵ Sandeep Kaushik,⁶ Shivam Chaturvedi,¹ Gobardhan Das,⁷ and Ved Prakash Dwivedi¹