Intranasal immunization with peptide-based immunogenic complex enhances BCG vaccine efficacy in a murine model of tuberculosis
Santosh Kumar, … , Gobardhan Das, Ved Prakash Dwivedi
Santosh Kumar, … , Gobardhan Das, Ved Prakash Dwivedi
Published January 14, 2021
Citation Information: JCI Insight. 2021;6(4):e145228. https://doi.org/10.1172/jci.insight.145228.
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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 4

PTL enhances the efficacy of BCG and protects mice against TB.

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PTL enhances the efficacy of BCG and protects mice against TB. (A) Lung ...
(A) Lung section to show the accumulation of liposomes. Liposomes were stained with PKH67 dye. Original magnification, ×100. (B) Quantification of the fluorescent images. (C) Layout to show the experimental plan wherein naive C57BL/6 mice or mice vaccinated with BCG/PTL or a combination of both were challenged with H37Rv via the aerosol route with a low-dose inoculum of ~150 CFU/mice. Mice were sacrificed at various time points, and lungs, spleen, and liver were harvested for observance of bacterial burden, as well as profiling of immune responses. (D) Lungs were harvested, preserved in 4% paraformaldehyde, and processed for sectioning and staining with H&E. Original magnification, ×100. (E) Quantification of the granuloma (inflammatory lesions) in all experimental groups. (F–H) CFU from the lung (F), spleen (G), and liver homogenates (H) at 50 days after infection. Two-tailed Student’s t test 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.