Safety and Immunogenicity of a 4-Component Generalized Modules for Membrane Antigens <i>Shigella</i> Vaccine in Healthy European Adults: Randomized, Phase 1/2 Study
Isabel Leroux‐Roels, Cathy Maes, Francesca Mancini, Bart Jacobs, Eleanna Sarakinou, Azhar Alhatemi, Jasper Joye, Silvia Grappi, Giulia Luna Cilio, Alimamy Serry-Bangura, Claudia Giorgina Vitali, Pietro Ferruzzi, Elisa Marchetti, Francesca Necchi, Rino Rappuoli, Iris De Ryck, Jochen Auerbach, Anna Colucci, Omar Rossi, Valentino Conti, Francesco Berlanda Scorza, Ashwani Kumar Arora, Francesca Micoli, Audino Podda, Usman Nakakana, the Shigella Project Team, Giulia Ranzato, Kishor Mariyala, Sateesh Aravapalli, Stefania Barbucci, Rob Mulder, Francesco Citiulo, Emilia Cappelletti, Gianmarco Gasperini, Carlo Giannelli, Alessandra Acquaviva, Luigi Sollai, Renzo Alfini, Maria Grazia Aruta, Laura B. Martin
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.