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- MetE: a promising protective antigen for tuberculosis vaccine developmentPublication . Almujri, Salem Salman; Stylianou, Elena; Nicastri, Annalisa; Satti, Iman; Korompis, Marcellus; Li, Shuailin; Voss, Christopher J. De; Alvarez, Marco Polo Peralta; Tanner, Rachel; Bettencourt, Paulo J. G.; Ternette, Nicola; McShane, HelenIntroduction: Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), remains a significant global health concern. The existing vaccine, Bacillus Calmette-Guérin (BCG), provides inconsistent protection, highlighting the pressing need for a more effective vaccine. We aimed to identify novel MTB antigens and assess their protective efficacy as TB vaccine candidates. Methods: Using immunopeptidomics, we identified 64 and 80 unique mycobacterial antigens derived from BCG and MTB, respectively. We prioritised antigens based on HLA allele coverage through an immunoinformatics approach. Results: The candidates, hisD, metE, and mmpL12, delivered as DNA vaccines, were evaluated for efficacy in mice using the ex vivo Mycobacterial Growth Inhibition Assay (MGIA) and metE was identified as a promising candidate. In vivo murine MTB challenge experiments confirmed the protective efficacy conferred by metE when formulated as recombinant protein with AS01™ or AddaS03™ adjuvants, compared to the naïve group. The immunogenic profiles of metE formulated in the two different adjuvants differed, with metE-AS01™ inducing antigen-specific IFN-?, TNF-?, IL-2, IL-17, IgG1 and IgG2a-c, while metE-AddaS03™ induced TNF-?, IL-2, IL-17, IL-4, IgM, IgG1, IgG2b. Conclusion: Our findings highlight metE as a promising protective antigen for future TB vaccine development.