TY - JOUR 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 T1 - Intranasal immunization with peptide-based immunogenic complex enhances BCG vaccine efficacy in a murine model of tuberculosis PY - 2021/02/22/ 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. JF - JCI Insight JA - JCI Insight SN - 2379-3708 DO - 10.1172/jci.insight.145228 VL - 6 IS - 4 UR - https://doi.org/10.1172/jci.insight.145228 PB - The American Society for Clinical Investigation ER -