Immune response characterization after controlled infection with lyophilized shigella sonnei 53G

Kristen A. Clarkson, Robert W. Frenck, Michelle Dickey, Akamol E. Suvarnapunya, Lakshmi Chandrasekaran, Hailey P. Weerts, Christopher D. Heaney, Monica McNeal, Kate Detizio, Susan Parker, Amy Hoeper, August L. Bourgeois, Chad K. Porter, Malabi M. Venkatesan, Robert W. Kaminski

Research output: Contribution to journalArticlepeer-review

Abstract

Shigella is a major cause of moderate to severe diarrhea largely affecting children (< 5 years old) living in low-and middle-income countries. Several vaccine candidates are in development, and controlled human infection models (CHIMs) can be useful tools to provide an early assessment of vaccine efficacy and potentially support licensure. A lyophilized strain of S. sonnei 53G was manufactured and evaluated to establish a dose that safely and reproducibly induced a ≥ 60% attack rate. Samples were collected pre-and postchallenge to assess intestinal inflammatory responses, antigen-specific serum and mucosal antibody responses, functional antibody responses, and memory B cell responses. Infection with S. sonnei 53G induced a robust intestinal inflammatory response as well as antigen-specific antibodies in serum and mucosal secretions and antigen-specific IgA-and IgG-secreting B cells positive for the 47 gut-homing marker. There was no association between clinical disease outcomes and systemic or functional antibody responses postchallenge; however, higher lipopolysaccharide (LPS)-specific serum IgA-and IgA-secreting memory B cell responses were associated with a reduced risk of disease postchallenge. This study provides unique insights into the immune responses pre-and postinfection with S. sonnei 53G in a CHIM, which could help guide the rational design of future vaccines to induce protective immune responses more analogous to those triggered by infection.

Original languageEnglish (US)
Article number988
JournalmSphere
Volume5
Issue number5
DOIs
StatePublished - Sep 2020

Keywords

  • Antibody
  • Controlled human infection model
  • Gut homing
  • Gut-homing responses
  • Immunogenicity
  • Immunological memory
  • Shigella
  • Shigella sonnei

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

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