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Putative correlates of protection against shigellosis assessing immunomarkers across responses to S. sonnei investigational vaccine.

Valentino ContiOmar RossiKristen A ClarksonFrancesca ManciniUsman Nasir NakakanaEleanna SarakinouAndrea CallegaroPietro FerruzziAlessandra AcquavivaAshwani Kumar AroraElisa MarchettiFrancesca NecchiRobert W FrenckLaura B MartinRobert W KaminskiAudino PoddaFrancesca Micoli
Published in: NPJ vaccines (2024)
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.
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