A lipidated peptide of Mycobacterium tuberculosis resuscitates the protective efficacy of BCG vaccine by evoking memory T cell immunity

Journal of Translational Medicine

Research

Javed N. Agrewala¹  Pradeep K. Rai¹  Sajid Nadeem¹  Sudeep K. Maurya¹  Susanta Pahari¹  Sathi Babu Chodisetti²  Weiguang Zeng³  David C. Jackson³  Ashok K. Janmeja⁴ 

[1] CSIR-Institute of Microbial Technology, Chandigarh, India;CSIR-Institute of Microbial Technology, Chandigarh, India;Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, 17033, Hershey, PA, USA;Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, 3010, Parkville, VIC, Australia;Department of Pulmonary Medicine, Government Medical College and Hospital, Chandigarh, India;

关键词: Vaccine;    BCG;    L91;    TB;    Mtb;    Th1;    Th17;    Memory T cells;   

DOI  :  10.1186/s12967-017-1301-x

 received in 2017-05-26, accepted in 2017-09-14,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundThe current BCG vaccine induces only short-term protection against Mycobacterium tuberculosis (Mtb), suggesting its failure to generate long-lasting memory T cells. Previously, we have demonstrated that a self-adjuvanting peptide of Mtb (L91), successfully generated enduring memory Th1 cells. Consequently, we investigated if L91 was able to recuperate BCG potency in perpetuating the generation of memory T cells and protection against Mtb infected mice.MethodsIn the present study, we evaluated the potency of a self adjuvanting Mtb peptide vaccine L91 in invigorating BCG immune response against Mtb in mice. Female BALB/c mice were immunized with BCG. Later, they were boosted twice with L91 or an antigenically irrelevant lipidated influenza virus hemagglutinin peptide (LH). Further, PBMCs obtained from BCG vaccinated healthy subjects were cultured in vitro with L91. T cell responses were determined by surface markers and intracellular cytokine staining. Secretion of cytokines was estimated in the culture supernatants (SNs) by ELISA.ResultsCompared to the BCG-vaccinated controls, L91 booster significantly enhanced the percentage of memory Th1 cells and Th17 cells and reduced the mycobacterial burden in BCG primed and L91-boosted (BCG-L91) group, even after 229 days of BCG vaccination. Further, substantial augmentation in the central (CD44hiCD62LhiCD127hi) and effector memory (CD44hiCD62LloCD127lo) CD4 T cells was detected. Furthermore, greater frequency of polyfunctional Th1 cells (IFN-γ+TNF-α+) and Th17 cells (IFN-γ+IL-17A+) was observed. Importantly, BCG-L91 successfully prevented CD4 T cells from exhaustion by decreasing the expression of PD-1 and Tim-3. Additionally, augmentation in the frequency of Th1 cells, Th17 cells and memory CD4 T cells was observed in the PBMCs of the BCG-vaccinated healthy individuals following in vitro stimulation with L91.ConclusionsOur study demonstrated that L91 robustly reinvigorate BCG potency to invoke enduring protection against Mtb. This novel vaccination stratagem involving BCG-priming followed by L91-boosting can be a future prophylactic measure to control TB.

【 授权许可】

CC BY   
© The Author(s) 2017