DEVELOPMENT AND EVALUATION OF hemA MUTANTS OF Vibrio cholerae 0139 BENGAL AS A POTENTIAL VACCINE
| dc.contributor.author | ALI, SYED ATIF | |
| dc.date.accessioned | 2016-01-12T03:26:57Z | |
| dc.date.available | 2016-01-12T03:26:57Z | |
| dc.date.issued | 2005-02 | |
| dc.description.abstract | This thesis describes the development of live attenuated oral vaccine strains VCUSMI and VCUSM2 against Vibrio cholerae 0139 Bengal. These strains are metabolic auxotrophs and require exogenous aminolevulinic acid (ALA) for their survival. The auxotrophy is achieved by mutating a house-keeping gene hemA that encodes for glutamyl tRNA reductase, an important enzyme of the C5 pathway of ALA biosynthesis. Experiments carried out in infant mice and adult rabbits have shown that these vaccine strains are good colonizers of the small intestine. Subsequent experiments have revealed that these strains shed for a maximum of 4 days in the stool and elicit greater than a four fold rise in vibriocidal antibodies in the vaccinated rabbits. Rabbits vaccinated with VCUSMI and VCUSM2 were fully protected against subsequent challenges with virulent wild type. Dose optimization studies have shown that as little as lxl06 CFU of VCUSMI and VCUSM2 given orally two weeks apart yielded 100% protection against subsequent challenge. Experiments carried out in ligated 'ileal loops of rabbits have shown that these strains are not absolutely non-reactogenic; however, they are 2.5 fold less toxic at doses of lxl06 CFU. VCUSMI and VCUSM2 survived no longer than 6 days in environmental waters as compared to the wild type that was detectable on day 20 post-inoculation. In summary, these results suggest that VCUSMI and VCUSM2 are promising least toxic and highly immunogenic vaccine candidates against V. cholerae 0139 Bengal. | en_US |
| dc.identifier.uri | http://hdl.handle.net/123456789/1370 | |
| dc.subject | DEVELOPMENT AND EVALUATION OF hemA MUTANTS OF Vibrio cholerae | en_US |
| dc.title | DEVELOPMENT AND EVALUATION OF hemA MUTANTS OF Vibrio cholerae 0139 BENGAL AS A POTENTIAL VACCINE | en_US |
| dc.type | Thesis | en_US |
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