Summary
This laboratory study characterised monoclonal antibodies isolated from a Shigella flexneri outbreak in non-human primates to inform rational vaccine design. Antibodies targeting the O-antigen demonstrated substantial affinity maturation and cross-reactivity, whilst antibodies against T3SS proteins (IpaD and IpaB) elicited robust responses but exhibited epitope-dependent effects on virulence. The findings reveal mechanisms of both protective and pathogenic immunity that could guide selection of safe and effective vaccine immunogens.
UK applicability
Shigella-related diarrhoea and antimicrobial resistance are global health challenges; insights from this vaccine development research are applicable to UK public health strategy and international vaccine deployment, though direct implementation would depend on clinical trial success and regulatory approval.
Key measures
Monoclonal antibody affinity maturation (>10%), cross-reactivity across S. flexneri serotypes, T cell and antibody response magnitude, epitope-specific effects on bacterial virulence in vitro and in vivo
Outcomes reported
The study isolated and characterised monoclonal antibodies against Shigella vaccine candidates from a non-human primate outbreak, identifying structural determinants of protective and deleterious immune responses. Key findings included affinity maturation of O-antigen antibodies with cross-reactivity and differential effects of T3SS antibodies on bacterial virulence.
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