Shigella

Shigella species are the cause of shigellosis, an enteric infection characterised by diarrhoea containing blood or mucus. The Shigella genus comprises four species; Shigella sonnei, Shigella flexneri, Shigella dysenteriae and Shigella boydii, with all but S. sonnei, encompassing several distinct serotypes. Shigellosis occurs worldwide across all age groups; however, they represent the greatest burden in children under 5 years of age in low- and middle-income countries (LMIC) where they are a leading cause of diarrhoeal mortality.

Current treatment relies on oral rehydration therapy and the use of antibiotics for dysentery in children in LMIC. Increasing antibiotic resistance in recent years demonstrates the need for development of a Shigella vaccine. Indeed, the Global Antimicrobial Resistance Surveillance System of the World Health Organisation (WHO) has highlighted Shigella as a high priority pathogen and since 2016 the WHO Product Development and Vaccines Advisory Committee prioritised Shigella vaccines to facilitate product development and pathway to policy.

We are currently working with the Future Vaccine Manufacturing Research (FVMR) hub and associated industrial partners on the development of vaccine candidates for LMIC.

Standardisation

We currently provide the WHO International Standard for Anti-dysentery (Shiga) serum (Equine) for use in toxin neutralisation assays and for calibration of anti-dysentery sera. With support of The Bill and Melinda Gates foundation, we are now developing a WHO International Standard for anti-shigella serum (Human) based on the most prevalent serotypes in circulation. This project will include a large international collaborative study. If you would be interested in participating in this collaborative study, then please contact us for more information.

Research

As part of the FVMR hub we work closely with a multidisciplinary team of academic and industrial scientists to develop new vaccines and production concepts for LMIC. This work is funded by Engineering and Physical Sciences Research Council (EPSRC) and the Department of Health and Social Care.

There are currently no licensed vaccines for Shigella infection; however, several candidates are being investigated at different stages of preclinical and clinical development. Candidates include polysaccharide-conjugates, whole-cell based and Generalised Modules for Membrane Antigens (GMMA), the majority of which, target the variable lipopolysaccharide (LPS) O-specific polysaccharide antigen. Given the diversity of Shigella species with 50 identified serotypes, and the increasing occurrence of AMR strains, the development of multi-component vaccines is of high importance.