Summary
This laboratory-based study leveraged samples from a non-human primate Shigella flexneri outbreak to isolate and characterise monoclonal antibodies against candidate vaccine antigens. Key findings include significant affinity maturation and broad cross-reactivity of O-antigen-targeting antibodies, and epitope-dependent dual roles of T3SS antibodies in modulating bacterial virulence. The structural insights provide evidence-based direction for rational Shigella vaccine immunogen design.
UK applicability
Shigella-related gastroenteritis remains a public health concern in the United Kingdom, particularly in institutional and immunocompromised populations. These vaccine design insights may inform future prevention strategies, though UK applicability depends on translating non-human primate immunology to human clinical development.
Key measures
Monoclonal antibody affinity maturation (>10%), cross-reactivity across S. flexneri serotypes, T cell and antibody responses to T3SS proteins (IpaD and IpaB), bacterial virulence inhibition and enhancement assays
Outcomes reported
The study isolated monoclonal antibodies against Shigella candidate vaccine antigens from a non-human primate outbreak and characterised structural and molecular determinants of protective versus deleterious immune responses. Findings identified affinity-matured antibodies with cross-reactivity and T3SS-targeting antibodies with epitope-dependent effects on bacterial virulence.
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