TY - JOUR
T1 - Intranasal immunization with peptide-based immunogenic complex enhances BCG vaccine efficacy in a murine model of tuberculosis
AU - Kumar, Santosh
AU - Bhaskar, Ashima
AU - Patnaik, Gautam
AU - Sharma, Chetan
AU - Singh, Dhiraj Kumar
AU - Kaushik, Sandeep Rai
AU - Chaturvedi, Shivam
AU - Das, Gobardhan
AU - Dwivedi, Ved Prakash
N1 - Funding Information:
We acknowledge the support of the DBT-supported Tuberculosis Aerosol Challenge Facility (TACF), at the ICGEB, and Animal House (ICGEB, New Delhi, India) and their staff in accomplishing this work. We would like to acknowledge Ranjan Kumar Nanda (Translational Health Group, ICGEB, New Delhi, India) for providing the resources for the study. VPD and AB are the recipients of the DST-INSPIRE Faculty Fellowship from Department of Science and Technology, Government of India (DST/INSPIRE/04/2014/002012 and DST/INSPIRE/04/2014/002069), and VPD is also recipient of Early Career Research Award from Science Engineering Recruitment Board (SERB; Department of Science and Technology, Government of India, ECR/2016/000294). We would like to acknowledge the funding support provided by ICGEB (New Delhi, India). The authors declare no competing financial interests.
Publisher Copyright:
© 2021, Kumar et al. This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License.
PY - 2021/2/22
Y1 - 2021/2/22
N2 - 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.
AB - 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.
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U2 - 10.1172/jci.insight.145228
DO - 10.1172/jci.insight.145228
M3 - Article
C2 - 33444288
AN - SCOPUS:85102143580
VL - 6
JO - JCI insight
JF - JCI insight
SN - 2379-3708
IS - 4
M1 - e145228
ER -