Immunogenicity and protective efficacy of Burkholderia pseudomallei BLF1-N and BLF1-C terminal domains against BLF1 toxin.

Immunogenicity and protective efficacy of Burkholderia pseudomallei BLF1-N and BLF1-C terminal domains against BLF1 toxin. Int Immunopharmacol. 2019 Oct 29;77:105917 Authors: Singh K, Singh AK, Uppalapati SR, Kingston JJ, Parida M Abstract Burkholderia lethal factor 1 (BLF1), a glutamine deamidase, is a key virulence factor that plays significant role in B. pseudomallei pathogenesis. To elucidate the BLF1 immunological responses, two truncated BLF1 structural units, BLF1-C (90-211 amino acids) with structural similarity to T. maritima Chemoreceptor glutamine deamidase (CheD) protein, and BLF1-N (1-89 amino acids) disparate to CheD were identified from the 23 kDa BLF1 protein. Both the components were devoid of toxicity in mice and elicited an antibody titer of 1:16,000 that reacted with the respective truncated proteins and BLF1. A549 cell lines supplemented with anti BLF1-N and BLF1-C antibodies exhibited 73.47% and 83.24% survival when treated with BLF1 toxin. Passive i.p. transfer with antibodies elicited by BLF1-C that contained LSGC active site resulted in 80% protection while anti BLF1-N (devoid of LSGC) antibodies provided 51.4% protection, establishing the role of BLF1-N terminal also in deamidase action. The truncated proteins also elicited cell mediated immune responses through proliferation of CD4+ T cells, IFN-γ and IL-4 cytokines but with bias towards Th2 subsets. BLF1-C and BLF1-N immunization resulted in 80% and 60%...
Source: International Immunopharmacology - Category: Allergy & Immunology Authors: Tags: Int Immunopharmacol Source Type: research