Immune Response Characterization after Controlled Infection with Lyophilized Shigella sonnei 53G

Area of Science:

• Infectious Diseases
• Immunology
• Vaccinology

Background:

• Shigella causes severe diarrhea, particularly in children in low- and middle-income countries.
• Controlled human infection models (CHIMs) are crucial for early vaccine efficacy assessment.
• Defining correlates of immunity for shigellosis is essential for vaccine development.

Purpose of the Study:

• To characterize immune responses following infection with Shigella sonnei 53G in a CHIM.
• To identify potential correlates of protection against shigellosis.
• To inform the design of effective Shigella vaccines.

Main Methods:

• A lyophilized Shigella sonnei 53G strain was used in a CHIM to establish a safe and reproducible infection dose.
• Immune responses, including inflammatory markers, antibody titers (serum and mucosal), and B cell populations, were measured pre- and post-challenge.
• Association between clinical outcomes and immune responses was analyzed.

Main Results:

• Shigella sonnei 53G infection induced robust intestinal inflammation and antigen-specific antibodies.
• Elevated baseline lipopolysaccharide (LPS)-specific serum IgA and IgA-secreting memory B cell responses were associated with a reduced risk of disease.
• No association was found between clinical disease and systemic or functional antibody responses post-challenge.

Conclusions:

• Immune responses in a Shigella sonnei CHIM provide insights into potential protective mechanisms.
• Baseline IgA responses may play a role in modulating disease severity and warrant further investigation as correlates of immunity.
• Findings can guide the development of Shigella vaccines inducing protective immune responses.