1. Development of a novel chimeric PA-LF antigen of Bacillus anthracis, its immunological characterization and evaluation as a future vaccine candidate in mouse model
- Author
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Vijai Pal, Manoj Kumar, Anshul Varshney, D.P. Nagar, and Ajay Kumar Goel
- Subjects
0301 basic medicine ,Recombinant Fusion Proteins ,Bacterial Toxins ,Bioengineering ,Anthrax Vaccines ,Applied Microbiology and Biotechnology ,Microbiology ,Anthrax ,03 medical and health sciences ,Chimera (genetics) ,Mice ,0302 clinical medicine ,Antigen ,Animals ,030212 general & internal medicine ,Pharmacology ,Antigens, Bacterial ,Mice, Inbred BALB C ,Anthrax vaccines ,General Immunology and Microbiology ,biology ,fungi ,Antibody titer ,Disease Management ,General Medicine ,biology.organism_classification ,Bacillus anthracis ,030104 developmental biology ,Humoral immunity ,biology.protein ,Drug Evaluation ,Female ,Bacterial antigen ,Antibody ,Biotechnology - Abstract
Tremendous efforts are being made to develop an anthrax vaccine with long term protection. The main component of traditional anthrax vaccine is protective antigen (PA) with the trace amount of other proteins and bacterial components. In this study, we developed a recombinant PA-LF chimera antigen of Bacillus anthracis by fusing the PA domain 2-4 with lethal factor (LF) domain 1 and evaluated its protective potential against B. anthracis in mouse model. The anti-PA-LF chimera serum reacted with both PA and LF antigen, individually. The chimera elicited a strong antibody titer in mice with predominance of IgG1 isotype followed by IgG2b, IgG2a and IgG3. Cytokines were assessed in splenocytes of immunized mice and a significant up-regulation in the expression of IL-4, IL-10, IFN-γ and TNF-α was observed. The PA-LF chimera immunized mice exhibited 80% survival after challenge with virulent spores of B. anthracis. Pathological studies showed normal architecture in vital organs (spleen, lung, liver and kidney) of recovered immunized mice on 20 DPI after spore challenge. These findings suggested that PA-LF chimera of B. anthracis elicited good humoral as well as cell mediated immune response in mice, and thus, can be a potent vaccine candidate against anthrax.
- Published
- 2019