PMID- 29375556
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220131
IS  - 1664-3224 (Print)
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 8
DP  - 2017
TI  - A Phase 2a Randomized Study to Evaluate the Safety and Immunogenicity of the 
      1790GAHB Generalized Modules for Membrane Antigen Vaccine against Shigella sonnei 
      Administered Intramuscularly to Adults from a Shigellosis-Endemic Country.
PG  - 1884
LID - 10.3389/fimmu.2017.01884 [doi]
LID - 1884
AB  - Shigellosis is a mild-to-severe diarrheal infection, caused by the genus 
      Shigella, and is responsible for significant morbidity and mortality worldwide. 
      We evaluated the safety and immunogenicity of an investigational Shigella sonnei 
      vaccine (1790GAHB) based on generalized modules for membrane antigens (GMMA) in 
      Kenya, a Shigella-endemic country. This phase 2a, observer-blind, controlled 
      randomized study (NCT02676895) enrolled 74 healthy adults aged 18-45 years, of 
      whom 72 were vaccinated. Participants received, in a 1:1:1 ratio, two 
      vaccinations with the 1790GAHB vaccine at doses of either 1.5/25 mug of O antigen 
      (OAg)/protein (group 1.5/25 mug) or 5.9/100 mug (group 5.9/100 mug) at day (D) 1 and 
      D29, or vaccination with a quadrivalent meningococcal vaccine at D1 and tetanus, 
      diphtheria, and acellular pertussis vaccine at D29 (control group). Solicited and 
      unsolicited adverse events (AEs), serious AEs (SAEs), and AEs of special interest 
      (neutropenia and reactive arthritis) were collected. Anti-S. sonnei 
      lipopolysaccharide (LPS) serum immunoglobulin G (IgG) geometric mean 
      concentrations (GMC) were evaluated at D1, D29, and D57 and compared to anti-S. 
      sonnei LPS antibody levels in convalescent patients naturally exposed to S. 
      sonnei. The percentages of participants with seroresponse were also calculated. 
      The most frequently reported solicited local and systemic AEs across all groups 
      were pain and headache, respectively. Only one case of severe systemic reaction 
      was reported (severe headache after first vaccination in group 5.9/100 mug). Seven 
      and three episodes of neutropenia, assessed as probably or possibly related to 
      vaccination respectively, were reported in the investigational and control 
      groups, respectively. No other SAEs were reported. Despite very high baseline 
      anti-S. sonnei LPS serum IgG levels, the 1790GAHB vaccine induced robust antibody 
      responses. At D29, GMC increased 2.10- and 4.43-fold from baseline in groups 
      1.5/25 and 5.9/100 mug, respectively, whereas no increase was observed in the 
      control group. Antibody titers at D57 were not statistically different from those 
      at D29. Seroresponse was 68% at D29 and 90% at D57 in group 1.5/25 mug, and 96% 
      after each vaccination in group 5.9/100 mug. The 1790GAHB vaccine was well 
      tolerated and highly immunogenic in a population of African adults, regardless of 
      the GMMA OAg/protein content used.
FAU - Obiero, Christina W
AU  - Obiero CW
AD  - KEMRI-Wellcome Trust Research Programme, Clinical Research Department, Kilifi, 
      Kenya.
FAU - Ndiaye, Augustin G W
AU  - Ndiaye AGW
AD  - GSK Vaccines Institute for Global Health, Siena, Italy.
FAU - Scire, Antonella Silvia
AU  - Scire AS
AD  - GSK Vaccines Institute for Global Health, Siena, Italy.
FAU - Kaunyangi, Bonface M
AU  - Kaunyangi BM
AD  - KEMRI-Wellcome Trust Research Programme, Clinical Research Department, Kilifi, 
      Kenya.
FAU - Marchetti, Elisa
AU  - Marchetti E
AD  - GSK Vaccines Institute for Global Health, Siena, Italy.
FAU - Gone, Ann M
AU  - Gone AM
AD  - KEMRI-Wellcome Trust Research Programme, Clinical Research Department, Kilifi, 
      Kenya.
FAU - Schutte, Lena Dorothee
AU  - Schutte LD
AD  - GSK Vaccines Clinical Laboratory Sciences, Marburg, Germany.
FAU - Riccucci, Daniele
AU  - Riccucci D
AD  - GSK Vaccines Institute for Global Health, Siena, Italy.
FAU - Auerbach, Joachim
AU  - Auerbach J
AD  - GSK Vaccines Institute for Global Health, Siena, Italy.
FAU - Saul, Allan
AU  - Saul A
AD  - GSK Vaccines Institute for Global Health, Siena, Italy.
FAU - Martin, Laura B
AU  - Martin LB
AD  - GSK Vaccines Institute for Global Health, Siena, Italy.
FAU - Bejon, Philip
AU  - Bejon P
AD  - Clinical Tropical Medicine, Nuffield Department of Medicine, University of 
      Oxford, Headington, United Kingdom.
FAU - Njuguna, Patricia
AU  - Njuguna P
AD  - KEMRI-Wellcome Trust Research Programme, Clinical Research Department, Kilifi, 
      Kenya.
AD  - Department of Public Health, Pwani University, Kilifi, Kenya.
FAU - Podda, Audino
AU  - Podda A
AD  - GSK Vaccines Institute for Global Health, Siena, Italy.
LA  - eng
GR  - G1002624/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
DEP - 20171222
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
PMC - PMC5763125
OTO - NOTNLM
OT  - 1790GAHB vaccine
OT  - Shigella sonnei
OT  - Shigella-endemic settings
OT  - generalized modules for membrane antigen
OT  - immunogenicity
OT  - safety
EDAT- 2018/01/30 06:00
MHDA- 2018/01/30 06:01
PMCR- 2017/01/01
CRDT- 2018/01/30 06:00
PHST- 2017/10/11 00:00 [received]
PHST- 2017/12/11 00:00 [accepted]
PHST- 2018/01/30 06:00 [entrez]
PHST- 2018/01/30 06:00 [pubmed]
PHST- 2018/01/30 06:01 [medline]
PHST- 2017/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2017.01884 [doi]
PST - epublish
SO  - Front Immunol. 2017 Dec 22;8:1884. doi: 10.3389/fimmu.2017.01884. eCollection 
      2017.