Vaccine Development for Shigella Infections

Shigella species remain a leading cause of bacillary dysentery worldwide, disproportionately affecting young children in low- and middle-income countries and contributing to antimicrobial resistance. Despite decades of research, no licensed vaccine is yet available, owing to challenges in eliciting durable mucosal immunity, navigating serotype diversity and defining correlates of protection. Vaccine constructs under study include live attenuated strains engineered to balance reactogenicity and immunogenicity, parenteral glycoconjugates targeting conserved O-antigen polysaccharides, bioconjugates produced by enzymatic linkage for enhanced manufacturability, subunit formulations of Type III secretion system proteins and outer membrane vesicle platforms. Novel delivery systems such as nanoparticle carriers aim to stabilise antigens and bypass cold-chain limitations. Preclinical models—from organ-on-chip microfluidic systems to zebrafish and oral mouse models—have accelerated antigen selection and adjuvant screening. Controlled human infection studies have provided proof of concept for bioconjugate candidates and defined serological thresholds associated with protection. Recent advances in high-throughput functional assays have enabled more efficient evaluation of bactericidal and opsonophagocytic antibody responses. As multiple candidates progress through phase I/II trials, integration of human challenge data with systems-immunology readouts will be critical to expediate licensure. A broadly protective vaccine against major serotypes such as S. flexneri 2a, 3a, 6 and S. sonnei—ideally formulated for needle-free delivery—would have profound impact on global child health and antimicrobial stewardship.

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Vaccine Development for Shigella Infections publication trend

The graph below shows the total number of articles in vaccine development for shigella infections across all publications each year (not limited to Nature Index journals).

Technical terms

Glycoconjugate vaccine: A vaccine in which bacterial polysaccharide antigens are covalently linked to a carrier protein to enhance immunogenicity.

Bioconjugate vaccine: A vaccine produced by enzymatic conjugation of bacterial polysaccharides to carrier proteins, enabling uniform and cost-effective manufacturability.

Lipopolysaccharide (LPS): A component of Gram-negative bacterial outer membranes that includes an O-antigen and acts as a target for antibody responses.

Serotype: A classification of bacteria based on antigenic properties of surface structures, particularly polysaccharide O antigens.

References

1. Facile synthesis of multi-faceted, biomimetic and cross-protective nanoparticle-based vaccines for drug-resistant Shigella: a flexible platform technology. Journal of Nanobiotechnology (2023).
2. Recent advances in modelling Shigella infection. Trends in Microbiology (2024).
3. Status of vaccine research and development for Shigella. Vaccine (2016).
4. Functional and Antigen-Specific Serum Antibody Levels as Correlates of Protection against Shigellosis in a Controlled Human Challenge Study. mSphere (2017).
5. The Shigella Vaccines Pipeline. Vaccines (2022).
6. Development of a high-throughput method to evaluate serum bactericidal activity using bacterial ATP measurement as survival readout. PLOS ONE (2017).
7. Human challenge study with a Shigella bioconjugate vaccine: Analyses of clinical efficacy and correlate of protection. EBioMedicine (2021).