Booster Vaccination With GVGH Shigella sonnei 1790GAHB GMMA Vaccine Compared to Single Vaccination in Unvaccinated Healthy European Adults: Results From a Phase 1 Clinical Trial

Front Immunol. 2019 Mar 8;10:335. doi: 10.3389/fimmu.2019.00335. eCollection 2019.

Abstract

The investigational Shigella sonnei vaccine (1790GAHB) based on GMMA (generalized modules for membrane antigens) is immunogenic, with an acceptable safety profile in adults. However, pre-vaccination anti-S. sonnei lipopolysaccharide (LPS) antibody levels seemed to impact vaccine-related immune responses. This phase 1, open-label, non-randomized extension study (ClinicalTrials.gov: NCT03089879) evaluated immunogenicity of a 1790GAHB booster dose in seven adults with undetectable antibodies prior to priming with three 1790GAHB vaccinations 2-3 years earlier (boosted group), compared to one dose in 28 vaccine-naïve individuals (vaccine-naïve group). Anti-S. sonnei LPS serum IgG geometric mean concentrations and seroresponse (increase of ≥25 EU or ≥50% from baseline antibody ≤ 50 EU and ≥50 EU, respectively) rates were calculated at vaccination (day [D]1), D8, D15, D29, D85. Safety was assessed. Geometric mean concentrations at D8 were 168 EU (boosted group) and 32 EU (vaccine-naïve group). Response peaked at D15 (883 EU) and D29 (100 EU) for the boosted and vaccine-naïve groups. Seroresponse rates at D8 were 86% (boosted group) and 24% (vaccine-naïve group) and increased at subsequent time points. Across both groups, pain (local) and fatigue (systemic) were the most frequent solicited adverse events (AEs). Unsolicited AEs were reported by 57% of boosted and 25% of vaccine-naïve participants. No deaths, serious AEs, or AEs of special interest (except one mild neutropenia case, possibly vaccination-related) were reported. One 1790GAHB dose induced a significant booster response in previously-primed adults, regardless of priming dose, and strong immune response in vaccine-naïve individuals. Vaccination was well tolerated.

Keywords: 1790GAHB; GMMA (generalized modules for membrane antigen); Shigella sonnei; antibody persistence; booster response; safety.

Publication types

  • Clinical Trial, Phase I

MeSH terms

  • Adult
  • Antibodies, Bacterial / blood
  • Female
  • Healthy Volunteers
  • Humans
  • Immunization, Secondary* / adverse effects
  • Immunoglobulin G / blood
  • Immunologic Memory
  • Lipopolysaccharides / immunology
  • Male
  • Middle Aged
  • Shigella Vaccines* / adverse effects
  • Shigella sonnei / immunology*
  • Vaccination / adverse effects
  • Vaccination / methods*

Substances

  • Antibodies, Bacterial
  • Immunoglobulin G
  • Lipopolysaccharides
  • Shigella Vaccines

Associated data

  • ClinicalTrials.gov/NCT03089879