Pre-Clinical and Clinical Validation of Vaccines Against Hemolytic Uremic Syndrome
Divya Sasitharan1, M. Masilamani Selvam1, Manohar Paul21Department of Biotechnology, Sathyabama University, Chennai, India 2Department of Microbiology,Tamil Nadu University of Veterinary and Animal Sciences,Chennai, India
Abstract: To compare the efficacy of a whole-cell vaccine and a toxoid vaccine prepared for Escherichia coli O157:H7 strain using rats as animal models after pre-clinical methods of testing. Methods: Isolation and identification of study strain from samples such as ground beef, chicken intestine, raw milk and pasteurized milk was followed by confirmation of five selected virulence genes by conventional PCR amplification. Whole cell vaccine and a toxoid vaccine, prepared as protein produced out of stx1 gene variant from an isolate strain of study were subjected to its efficacy test using bioinformatics tools, cell culture technique and clinical tests using rat models after obtaining proper ethical clearance. After challenging with ATCC and isolates, screening performed by histology in liver and kidney on test rats as well as on control rats. Results: Cytopathic effects of prepared vaccines in vero cell lines and SavesV4 software results showed loss of pathogenicity and retainment of immunogenicity of the study strain. Normal histology was seen in liver and kidney specimens of vaccinated and challenged rat groups as well as control un-inoculated unvaccinated rat groups with very few exceptional lesions. However, severe toxic evidences were observed in rat groups which were unvaccinated and challenged with pathogenic strains. Conclusions: Vaccine is believed to have lost its pathogenicity to a greater extent as validated by pre-clinical and animal studies. When comparison was made between whole cell vaccine and toxoid, whole cell vaccine had greater extent of efficiency than toxoid.
Keywords: Escherichia coli O157:H7; Toxoid Vaccine; Whole-cell vaccine; Haemolytic Uremic Syndrome Back to TOC