Immunogenicity and protective efficacy of a live, oral cholera vaccine formulation stored outside-the-cold-chain for 140 days.

Background: Cholera, an acute watery diarrhoeal disease caused by Vibrio cholerae serogroup O1 and O139 across the continents. Replacing the existing WHO licensed killed multiple-dose oral cholera vaccines that demand 'cold chain supply' at 2-8 °C with a live, single-dose and cold chain-free vaccine would relieve the significant bottlenecks and cost determinants in cholera vaccination campaigns. In this direction, a prototype cold chain-free live attenuated cholera vaccine formulation (LACV) was developed against the toxigenic wild-type (WT) V.

Repeated dose toxicity evaluation of a cold chain-free, live, attenuated oral cholera vaccine in Sprague Dawley rats.

The repeated dose toxicity of a prototype cold chain-free, live, attenuated oral cholera vaccine containing 5 × 10 CFU/mL of the VCUSM14P strain was evaluated in Sprague Dawley (SD) rats (single dose administered daily for 30 days) to ascertain its safety for clinical use. Repeated dose toxicity studies for cholera vaccines in the literature have administered 2 or 3 fixed doses at 7, 14, 21 or 69 day intervals. The present study reports an evaluation of 30 repeated doses of cholera vaccine administered at three different concentrations (Group II (1.

Construction and characterization of rtxA and rtxC mutants of auxotrophic O139 Vibrio cholerae.

Vibrio cholerae is a Gram-negative bacterium that causes diarrheal disease. V. cholerae O1 and O139 serogroups are toxigenic and are known to cause epidemic cholera.

Construction and evaluation of a O139 Vibrio cholerae vaccine candidate based on a hemA gene mutation.

In this paper, we describe the development of VCUSM2, a live metabolic auxotroph of Vibrio cholerae O139. Auxotrophy was achieved by mutating a house keeping gene, hemA, that encodes for glutamyl-tRNA reductase, an important enzyme in the C5 pathway for delta-aminolevulenic acid (ALA) biosynthesis, which renders this strain dependent on exogenous ALA for survival. Experiments using the infant mouse and adult rabbit models show that VCUSM2 is a good colonizer of the small intestine and elicits greater than a four-fold rise in vibriocidal antibodies in vaccinated rabbits.