Towards a conjugate vaccine based on anthrax protective antigen
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Abstract
Anthrax toxin is an AB toxin and made up of two components. The A components are Lethal Factor and Edema factor. B component is protective antigen (PA). PA is the part of the toxin that directly targets and disrupts host immune cells. PA has high affinity binding to capillary morphogenesis protein 2 (CMG2) which promotes cellular toxicity within the host cell. CMG2 is a receptor expressed on antigen presenting cells such as dendritic cells or macrophages. Antigen presenting cells can produce naïve and memory T cells, which helps with immunity towards a bacterium. We are looking at high affinity between PA and CMG2 specifically on dendritic cells to create a hybrids vaccine which will advance T cell levels. To test this, we are first looking at a conjugate between PA and Spy0469, a surface protein on Streptococcus pyogenes. We are looking at Spy0469 because humans already have high T cells which respond to Spy0469 due to infections in childhood. Using this information, we want to make a Pa conjugate based on the Spytag Spycatcher system. Spytag is a peptide that has a high binding affinity to the surface protein Spycatcher. Using PCR (Polymerase Chain Reaction) and mutagenesis we look at making a mutant E. coli bacterium.
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Research project completed at the Department of Chemistry and Biochemistry.