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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Efficacy, safety, and immunogenicity of the Shigella sonnei 1790GAHB GMMA candidate vaccine: Results from a phase 2b randomized, placebo-controlled challenge study in adults
EClinicalMedicine, Volume 39, Article 101076, Year 2021
Notification
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Description
Background: Shigellosis accounts for substantial morbidity and mortality worldwide and is the second most common cause of moderate and severe diarrhoea in children. Methods: This phase 2b study (NCT03527173), conducted between August 2018 and November 2019, evaluated vaccine efficacy (VE), safety, and immunogenicity of a Shigella sonnei GMMA candidate vaccine (1790GAHB) in adults, using a S. sonnei 53 G controlled human infection model. Participants (randomized 1:1) received two doses of 1790GAHB or placebo (GAHB-Placebo), at day (D) 1 and D29, and an oral challenge of S. sonnei 53 G at D57. VE was evaluated using several endpoints, reflecting different case definitions of shigellosis. For the primary endpoint, the success criterion was a lower limit of the 90% confidence interval >0. Findings: Thirty-six and 35 participants received 1790GAHB or placebo, respectively; 33 and 29 were challenged, 15 and 12 developed shigellosis. VE was not demonstrated for any endpoint. Adverse events were more frequent in 1790GAHB versus placebo recipients post-vaccination. Anti-S. sonnei lipopolysaccharide (LPS) IgG responses increased at D29 and remained stable through D57 in group 1790GAHB; no increase was shown in placebo recipients. Interpretation: 1790GAHB had an acceptable safety profile and induced anti-LPS IgG responses but did not demonstrate clinical efficacy against shigellosis. Baseline/pre-challenge antibody levels were higher in participants who did not develop shigellosis post-challenge, suggesting a role of anti-LPS IgG antibodies in clinical protection, although not fully elucidated in this study. For further vaccine development an increased S. sonnei O-antigen content is likely needed to enhance anti-LPS immune responses. Funding: GlaxoSmithKline Biologicals SA, Bill and Melinda Gates Foundation © 2021 The Author(s)
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC8367798/bin/mmc1.docx
Authors & Co-Authors
Frenck, Robert W.
United States, Cincinnati
Cincinnati Children's Hospital Medical Center
Conti, Valentino
Italy, Verona
Glaxosmithkline Spa
Ndiaye, Augustin G.W.
Italy, Verona
Glaxosmithkline Spa
McNeal, Monica Malone
United States, Cincinnati
Cincinnati Children's Hospital Medical Center
United States, Cincinnati
University of Cincinnati College of Medicine
de Ryck, Iris
Italy, Verona
Glaxosmithkline Spa
Necchi, Francesca
Italy, Verona
Glaxosmithkline Spa
Suvarnapunya, Akamol Eddie
United States, Silver Spring
Walter Reed Army Institute of Research
Rossi, Omar
Italy, Verona
Glaxosmithkline Spa
Acquaviva, Alessandra
Italy, Verona
Glaxosmithkline Spa
Auerbach, Joachim
Italy, Verona
Glaxosmithkline Spa
Marchetti, Elisa
Italy, Verona
Glaxosmithkline Spa
Kaminski, Robert W.
United States, Silver Spring
Walter Reed Army Institute of Research
Micoli, Francesca
Italy, Verona
Glaxosmithkline Spa
Rappuoli, Rino
Italy, Verona
Glaxosmithkline Spa
Saul, Allan
Italy, Verona
Glaxosmithkline Spa
Martin, Laura B.
Italy, Verona
Glaxosmithkline Spa
Podda, Audino
Italy, Verona
Glaxosmithkline Spa
Statistics
Citations: 36
Authors: 17
Affiliations: 4
Identifiers
Doi:
10.1016/j.eclinm.2021.101076
ISSN:
25895370
Research Areas
Health System And Policy
Infectious Diseases
Maternal And Child Health