GMMA Technology for the Development of Safe Vaccines: Meta-Analysis of Individual Patient Data to Assess the Safety Profile of Shigella sonnei 1790GAHB Vaccine in Healthy Adults, with Special Focus on Neutropenia

Abstract

Introduction Shigellosis is a major health concern among children < 5 years of age from developing countries, and there are no widely available vaccines to prevent it. The GMMA-based 1790GAHB investigational vaccine against Shigella sonnei was well tolerated and immunogenic in phase 1 and 2 studies conducted in healthy adults from Shigella endemic and non-endemic populations. Based on pooled data of five individual trials, we assessed the association between vaccine administration and the risk of neutropenia as well as the overall safety profile of 1790GAHB. Methods The risk ratio (RR) of neutropenia was evaluated between participants receiving 1790GAHB (vaccinees) and active comparator/placebo (controls) using different ethnicity-specific absolute neutrophil count (ANC) thresholds established to define neutropenia. Safety was assessed in terms of solicited, unsolicited, and serious adverse events (AEs). Results Of the 279 participants, 11 (5.5%) vaccinees and 4 (5.0%) controls had ANC below the appropriate threshold within 7 days post-vaccination. RR was 0.96 [95% confidence interval (CI) 0.54–1.70]. When neutrophil counts of participants of African descent were measured against an ethnicity non-specific threshold, they resulted in neutropenia episodes in 30 (37.0%) vaccinees and 16 (30.2%) controls, while only 2 (2.5%) vaccinees and 1 (1.9%) control had neutropenia when the ethnicity-specific threshold was applied. RRs were 0.98 (95% CI 0.75–1.28) and 1.30 (95% CI 0.1–17.6), respectively. Solicited and unsolicited AEs were slightly more frequent among vaccinees than controls. No serious AEs, other than neutropenia cases, were recorded in the vaccine group. Conclusion By applying the appropriate threshold, no increased risk of neutropenia was identified in vaccinees compared with the controls. The frequency of neutropenia events varied drastically when ethnicity-appropriate thresholds were applied. This observation highlights the importance of selecting appropriate cut-off values according to the correct population reference. Overall, the 1790GAHB vaccine demonstrated an acceptable safety profile. Supplementary Information The online version contains supplementary material available at 10.1007/s40121-022-00596-x.

Microbial metabolites are involved in tumorigenesis and development by regulating immune responses

“…Gerke C et al. designed a vaccine (1790GAHB) against Shigella sonnei using the generalized membrane antigen module (GMMA) technology using the O-antigen (OAg) fraction of LPS as the active fraction ( 213 ), which has been proved to be effective and safe by phase II clinical trials ( 214 ). Riddle MS et al.…”

“…For example, the Shigella is a pathogenic bacteria agent of severe diarrhea and dysentery. Gerke C et al designed a vaccine (1790GAHB) against Shigella sonnei using the generalized membrane antigen module (GMMA) technology using the O-antigen (OAg) fraction of LPS as the active fraction (213), which has been proved to be effective and safe by phase II clinical trials (214). Riddle MS et al conjugated the polysaccharide component of the O-antigen of S. flexneri 2a to exotoxin protein A of Pseudomonas aeruginosa (EPA) and developed a novel bioconjugate vaccine (Flexyn2a) against S. flexneri 2a (215), which have been proved promising (216).…”