171. Efficacy and Immunogenicity of WRSs2, a Live Attenuated Shigella sonnei Vaccine Candidate, to Protect Against Shigellosis After Challenge with a Wild-type S. sonnei strain 53G

Abstract

Background

Shigella is a leading cause of bacterial diarrhea. The live attenuated S. sonnei vaccine candidate WRSs2, lacking virG (icsA), senA, and senB, was evaluated for its efficacy in preventing shigellosis.

Serum LPS IgG GMT, By Group Over Time

Stool Shedding, WRSs2

Methods

Adults aged 18-49 years received 2 doses of study product 28 days apart (1 or 2 doses of 10⁶ colony forming units (cfu) of WRSs2 or placebo). 4 weeks after vaccination, using a controlled human infection model (CHIM), participants were administered 1500 cfu of virulent S. sonnei (53G) in an inpatient unit. After challenge, participants were evaluated daily and stools were graded and cultured for Shigella. 5 days post-challenge, ciprofloxacin (500 mg BID x 3 days) was administered. Discharge home was based on antibiotic completion and 2 stool cultures negative for S. sonnei. Blood samples were collected at various times after each vaccination as well as after challenge. Shigellosis was defined as signs and symptoms of Shigella along with Shigella isolated from the stool. Vaccine efficacy was calculated as 1 – (attack rate of shigellosis in WRSs2 group /attack rate of shigellosis in placebo group).

Stool Shedding (53G) After Challenge, By Culture

Efficacy of WRSs2 in Prevention of Shigellosis After Challenge with 53G

Results

108 participants were randomized to receive 1 or 2 doses of WRSs2 (n=23 and n=48 respectively) or 2 doses of placebo (n=37). 73 participants (13 one-dose WRSs2, 34 two-dose WRSs2, 26 placebo) received a dose of 53G. The vaccine was generally well tolerated. 2 participants developed Grade 3 diarrhea with no alternative etiology resulting in a vaccine dose reduction to 5x10⁵ cfu and limiting remaining enrollments to two arms (2 doses WRSs2 vs. 2 doses placebo).

Among participants receiving 2 doses of WRSs2, vaccine efficacy was 89% (95% CI: 71-96%), p< 0.001 (9% shigellosis in vaccinees vs 81% in placebo recipients). No participant in the 1 dose WRSs2 group developed shigellosis (VE=100% (95% CI: 71-100%)).

Following vaccination, most participants mounted serum IgA and IgG responses to Invaplex and LPS. The responder rates to these antigen or isotypes among vaccine recipients varied from 45-73% vs 0-6% among placebo recipients.

Conclusion

Using a S. sonnei CHIM, the live attenuated oral S. sonnei vaccine WRSs2 demonstrated high efficacy against shigellosis. These findings support further evaluation of WRSs2 in field trials to assess its effectiveness in endemic settings.

Disclosures

All Authors: No reported disclosures