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Pro-Glu/Pro-Pro-Glu (PE/PPE) family proteins in Mycobacterium tuberculosis (Mtb) are contributors to pathogenesis and immune evasion. These proteins have a unique structure in which the sequence is conserved. We investigated the vaccine potential of ESAT-6 fused with the consensus CD4 T-cell epitopes of PE/PPE proteins against a highly pathogenic Mtb strain HN878 in a murine model.We selected the consensus CD4 T-cell epitopes of PE/PPE proteins by multiple alignments and by investigating their IFN-γ response during Mtb infection, and produced their fused ESAT-6 vaccine antigens. Our results showed that an increased immune response was observed in the PE/PPE peptide + ESAT-6 protein immunization group compared with that in the ESAT-6 only immunization group. After challenging with Mtb, we observed induced CD4 T-cells secreting double-positive cytokine IL-2/IFN-γ, which is associated with protective T-cell immunity. Also, lower numbers of colony-forming units were observed in the spleen of the fusion protein immunization groups than in the single ESAT-6 group. Thus, conjugation of the consensus CD4 T-cell epitopes in N terminus of PE/PPE to vaccine antigens could potentially increase the protective efficacy of as a subunit vaccine.
This article was published in the following journal.
Name: Biochemical and biophysical research communications
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