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

Valentino Conti; Omar Rossi; Kristen A Clarkson; Francesca Mancini; Usman N Nakakana; Eleanna Sarakinou; Andrea Callegaro; Pietro Ferruzzi; Alessandra Acquaviva; Ashwani Kumar Arora; Elisa Marchetti; Francesca Necchi; Robert W Frenck Jr; Laura B Martin; Robert W Kaminski; Audino Podda; Francesca Micoli

doi:10.1038/s41541-024-00822-2

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

NPJ Vaccines. 2024 Mar 8;9(1):56. doi: 10.1038/s41541-024-00822-2.

Authors

Valentino Conti¹, Omar Rossi¹, Kristen A Clarkson^{2

3}, Francesca Mancini¹, Usman N Nakakana⁴, Eleanna Sarakinou¹, Andrea Callegaro⁵, Pietro Ferruzzi¹, Alessandra Acquaviva¹, Ashwani Kumar Arora¹, Elisa Marchetti¹, Francesca Necchi¹, Robert W Frenck Jr⁶, Laura B Martin^{1

7}, Robert W Kaminski^{2

8}, Audino Podda^{1

9}, Francesca Micoli¹

Affiliations

¹ GSK Vaccines Institute for Global Health, Siena, Italy.
² Department of Diarrheal Disease Research, Bacterial Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
³ Horizon Therapeutics, Deerfield, IL, USA.
⁴ GSK Vaccines Institute for Global Health, Siena, Italy. usman.n.nakakana@gsk.com.
⁵ GSK, Rixensart, Belgium.
⁶ Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
⁷ US Pharmacopeial Convention, Rockville, MD, USA.
⁸ Latham BioPharm Group, Cambridge, MA, USA.
⁹ Independent Consultant, Siena, Italy.

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.