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ResearchIn-Press PreviewImmunologyInfectious disease Open Access | 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

1Department of Immunobiology, International Centre for Genetic Engineering and Biotechnology, New Delhi, India

2Signal Transduction Laboratory-1, National Institute of Immunology, New Delhi, India

3Department of Molecular Medicine, Jawaharlal Nehru University, New Delhi, India

4Department of Immunobiology, International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India

5Molecular Medicine, Jawaharlal Nehru University, New Delhi, India

6Department of Immunology, International Centre for Genetic Engineering and Biotechnology, New Delhi, India

7Center for Molecular Medicine, Jawaharlal Nehru University, New Delhi, India

Find articles by Kumar, S. in: JCI | PubMed | Google Scholar |

1Department of Immunobiology, International Centre for Genetic Engineering and Biotechnology, New Delhi, India

2Signal Transduction Laboratory-1, National Institute of Immunology, New Delhi, India

3Department of Molecular Medicine, Jawaharlal Nehru University, New Delhi, India

4Department of Immunobiology, International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India

5Molecular Medicine, Jawaharlal Nehru University, New Delhi, India

6Department of Immunology, International Centre for Genetic Engineering and Biotechnology, New Delhi, India

7Center for Molecular Medicine, Jawaharlal Nehru University, New Delhi, India

Find articles by Bhaskar, A. in: JCI | PubMed | Google Scholar

1Department of Immunobiology, International Centre for Genetic Engineering and Biotechnology, New Delhi, India

2Signal Transduction Laboratory-1, National Institute of Immunology, New Delhi, India

3Department of Molecular Medicine, Jawaharlal Nehru University, New Delhi, India

4Department of Immunobiology, International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India

5Molecular Medicine, Jawaharlal Nehru University, New Delhi, India

6Department of Immunology, International Centre for Genetic Engineering and Biotechnology, New Delhi, India

7Center for Molecular Medicine, Jawaharlal Nehru University, New Delhi, India

Find articles by Patnaik, G. in: JCI | PubMed | Google Scholar

1Department of Immunobiology, International Centre for Genetic Engineering and Biotechnology, New Delhi, India

2Signal Transduction Laboratory-1, National Institute of Immunology, New Delhi, India

3Department of Molecular Medicine, Jawaharlal Nehru University, New Delhi, India

4Department of Immunobiology, International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India

5Molecular Medicine, Jawaharlal Nehru University, New Delhi, India

6Department of Immunology, International Centre for Genetic Engineering and Biotechnology, New Delhi, India

7Center for Molecular Medicine, Jawaharlal Nehru University, New Delhi, India

Find articles by Sharma, C. in: JCI | PubMed | Google Scholar |

1Department of Immunobiology, International Centre for Genetic Engineering and Biotechnology, New Delhi, India

2Signal Transduction Laboratory-1, National Institute of Immunology, New Delhi, India

3Department of Molecular Medicine, Jawaharlal Nehru University, New Delhi, India

4Department of Immunobiology, International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India

5Molecular Medicine, Jawaharlal Nehru University, New Delhi, India

6Department of Immunology, International Centre for Genetic Engineering and Biotechnology, New Delhi, India

7Center for Molecular Medicine, Jawaharlal Nehru University, New Delhi, India

Find articles by Singh, D. in: JCI | PubMed | Google Scholar |

1Department of Immunobiology, International Centre for Genetic Engineering and Biotechnology, New Delhi, India

2Signal Transduction Laboratory-1, National Institute of Immunology, New Delhi, India

3Department of Molecular Medicine, Jawaharlal Nehru University, New Delhi, India

4Department of Immunobiology, International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India

5Molecular Medicine, Jawaharlal Nehru University, New Delhi, India

6Department of Immunology, International Centre for Genetic Engineering and Biotechnology, New Delhi, India

7Center for Molecular Medicine, Jawaharlal Nehru University, New Delhi, India

Find articles by Kaushik, S. in: JCI | PubMed | Google Scholar |

1Department of Immunobiology, International Centre for Genetic Engineering and Biotechnology, New Delhi, India

2Signal Transduction Laboratory-1, National Institute of Immunology, New Delhi, India

3Department of Molecular Medicine, Jawaharlal Nehru University, New Delhi, India

4Department of Immunobiology, International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India

5Molecular Medicine, Jawaharlal Nehru University, New Delhi, India

6Department of Immunology, International Centre for Genetic Engineering and Biotechnology, New Delhi, India

7Center for Molecular Medicine, Jawaharlal Nehru University, New Delhi, India

Find articles by Chaturvedi, S. in: JCI | PubMed | Google Scholar

1Department of Immunobiology, International Centre for Genetic Engineering and Biotechnology, New Delhi, India

2Signal Transduction Laboratory-1, National Institute of Immunology, New Delhi, India

3Department of Molecular Medicine, Jawaharlal Nehru University, New Delhi, India

4Department of Immunobiology, International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India

5Molecular Medicine, Jawaharlal Nehru University, New Delhi, India

6Department of Immunology, International Centre for Genetic Engineering and Biotechnology, New Delhi, India

7Center for Molecular Medicine, Jawaharlal Nehru University, New Delhi, India

Find articles by Das, G. in: JCI | PubMed | Google Scholar

1Department of Immunobiology, International Centre for Genetic Engineering and Biotechnology, New Delhi, India

2Signal Transduction Laboratory-1, National Institute of Immunology, New Delhi, India

3Department of Molecular Medicine, Jawaharlal Nehru University, New Delhi, India

4Department of Immunobiology, International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India

5Molecular Medicine, Jawaharlal Nehru University, New Delhi, India

6Department of Immunology, International Centre for Genetic Engineering and Biotechnology, New Delhi, India

7Center for Molecular Medicine, Jawaharlal Nehru University, New Delhi, India

Find articles by Dwivedi, V. in: JCI | PubMed | Google Scholar

Published January 14, 2021 - More info

JCI Insight. https://doi.org/10.1172/jci.insight.145228.
Copyright © 2021, Kumar et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published January 14, 2021 - Version history
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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.

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