Safety and Immunogenicity of a 4-Component Generalized Modules for Membrane Antigens Shigella Vaccine in Healthy European Adults: Randomized, Phase 1/2 Study

Abstract Background We report data from stage 1 of an ongoing 2-staged, phase 1/2 randomized clinical trial with a 4-component generalized modules for membrane antigens-based vaccine against Shigella sonnei and Shigella flexneri 1b, 2a, and 3a (altSonflex1-2-3; GSK). Methods Europeans aged 18–50 yea...

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Published in:The Journal of infectious diseases 2024-06
Main Authors: Leroux-Roels, Isabel, Maes, Cathy, Mancini, Francesca, Jacobs, Bart, Sarakinou, Eleanna, Alhatemi, Azhar, Joye, Jasper, Grappi, Silvia, Cilio, Giulia Luna, Serry-Bangura, Alimamy, Vitali, Claudia G, Ferruzzi, Pietro, Marchetti, Elisa, Necchi, Francesca, Rappuoli, Rino, De Ryck, Iris, Auerbach, Jochen, Colucci, Anna M, Rossi, Omar, Conti, Valentino, Scorza, Francesco Berlanda, Arora, Ashwani Kumar, Micoli, Francesca, Podda, Audino, Nakakana, Usman N, Ranzato, Giulia, Mariyala, Kishor, Aravapalli, Sateesh, Barbucci, Stefania, Mulder, Rob, Citiulo, Francesco, Cappelletti, Emilia, Gasperini, Gianmarco, Giannelli, Carlo, Acquaviva, Alessandra, Sollai, Luigi, Alfini, Renzo, Aruta, Maria Grazia, Martin, Laura Bartle
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Language:English
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Summary:Abstract Background We report data from stage 1 of an ongoing 2-staged, phase 1/2 randomized clinical trial with a 4-component generalized modules for membrane antigens-based vaccine against Shigella sonnei and Shigella flexneri 1b, 2a, and 3a (altSonflex1-2-3; GSK). Methods Europeans aged 18–50 years (N = 102) were randomized (2:1) to receive 2 injections of altSonflex1-2-3 or placebo at 3- or 6-month interval. Safety and immunogenicity were assessed at prespecified time points. Results The most common solicited administration-site event (until 7 days after each injection) and unsolicited adverse event (until 28 days after each injection) were pain (altSonflex1-2-3, 97.1%; placebo, 58.8%) and headache (32.4%; 23.5%), respectively. All serotype-specific functional IgG antibodies peaked 14–28 days after injection 1 and remained substantially higher than prevaccination at 3 or 6 months postvaccination; the second injection did not boost but restored the initial immune response. The highest seroresponse rates (≥4-fold increase in titers over baseline) were obtained against S. flexneri 2a (enzyme-linked immunosorbent assay [ELISA] after injection 1, 91.0%; after injection 2 [day 113; day 197], 100%; 97.0% and serum bactericidal activity [SBA] after injection 1, 94.4%; after injection 2, 85.7%; 88.9%) followed by S. sonnei (ELISA after injection 1, 77.6%; after injection 2, 84.6%; 78.8% and SBA after injection 1, 83.3%; after injection 2, 71.4%; 88.9%). Immune responses against S. flexneri 1b and S. flexneri 3a, as measured by both ELISA and SBA, were numerically lower compared to those against S. sonnei and S. flexneri 2a. Conclusions No safety signals or concerns were identified. altSonflex1-2-3 induced functional serotype-specific immune responses, allowing further clinical development in the target population. Clinical Trials Registration . NCT05073003.
ISSN:0022-1899
1537-6613
DOI:10.1093/infdis/jiae273