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- Title
Putative correlates of protection against shigellosis assessing immunomarkers across responses to S. sonnei investigational vaccine.
- Authors
Conti, Valentino; Rossi, Omar; Clarkson, Kristen A.; Mancini, Francesca; Nakakana, Usman N.; Sarakinou, Eleanna; Callegaro, Andrea; Ferruzzi, Pietro; Acquaviva, Alessandra; Arora, Ashwani Kumar; Marchetti, Elisa; Necchi, Francesca; Frenck Jr, Robert W.; Martin, Laura B.; Kaminski, Robert W.; Podda, Audino; Micoli, Francesca
- Abstract
Shigella spp. are a leading bacterial cause of diarrhea. No widely licensed vaccines are available and there is no generally accepted correlate of protection. We tested a S. sonnei Generalized Modules for Membrane Antigen (GMMA)-based vaccine (1790GAHB) in a phase 2b, placebo-controlled, randomized, controlled human infection model study (NCT03527173) enrolling healthy United States adults aged 18–50 years. We report analyses evaluating immune responses to vaccination, with the aim to identify correlates of risk for shigellosis among assessed immunomarkers. We found that 1790GAHB elicited S. sonnei lipopolysaccharide specific α4β7+ immunoglobulin (Ig) G and IgA secreting B cells which are likely homing to the gut, indicating the ability to induce a mucosal in addition to a systemic response, despite parenteral delivery. We were unable to establish or confirm threshold levels that predict vaccine efficacy facilitating the evaluation of vaccine candidates. However, serum anti-lipopolysaccharide IgG and bactericidal activity were identified as potential correlates of risk for shigellosis.
- Subjects
UNITED States; SHIGELLOSIS; VACCINE effectiveness; VACCINES; B cells; IMMUNE response; SHIGELLA
- Publication
NPJ Vaccines, 2024, Vol 9, Issue 1, p1
- ISSN
2059-0105
- Publication type
Article
- DOI
10.1038/s41541-024-00822-2