Shigella sonnei live vaccine candidate WRSS1, which had previously been tested on volunteers in the United States, Israel, and Thailand, was given orally to Bangladeshi adults and children to examine its safety, clinical tolerability, and immunogenicity. 39 adults and 64 children were enrolled in a randomized, placebo-controlled, dose-escalation, age-descending trial. Each adult group was given one dosage of 3×104, three doses of 3105, or three doses of 3106 colony-forming unit (CFU) of WRSS1 or a placebo. Each kid group got one dosage of 3×103, three doses of 3×104, three doses of 3×105, or three doses of 3106 CFU WRSS1 or placebo. In adults and children, WRSS1 induced generally modest and transitory reactogenicity. The vaccine was shed by 50% of adults in the 3 106 dose group, but not by children. At the highest dosage, all adults and 40% of children had a 4-fold rise in S. sonnei LPS-specific IgA antibodies in lymphocyte supernatant (ALS). At the same dosage, IgA seroconverted 63 percent of adults and 70 percent of children to LPS, whereas placebo seroconverted 33 percent of adults and 18 percent of children. Both the vaccinees and the placebos produced fecal IgA in response to LPS, showing that they had been exposed to Shigella infections for an extended period of time.
Finally, in adults and children in Bangladesh, WRSS1 was found to be safe up to 106 CFU doses and immunogenic. These findings suggest that live, oral Shigella vaccine candidates, including WRSS1, may be tested in toddlers and babies, the target group in an endemic setting.
Reference: https://www.tandfonline.com/doi/full/10.1080/21645515.2019.1575165
