Journal Article

Status of vaccine research and development for Shigella

Wierzba, Thomas, Mani, Sachin, Walker, Richard I.

2016

Overview

•Shigella infections cause substantial mortality and morbidity in children and adults.•Results from animal studies and challenge models spur Shigella vaccine development.•Various immune mechanisms show potential for durable and protective mucosal response.•Several vaccines are being evaluated either alone or in association with an adjuvant. Shigella are gram-negative bacteria that cause severe diarrhea and dysentery. In 2013, Shigella infections caused an estimated 34,400 deaths in children less than five years old and, in 2010, an estimated 40,000 deaths in persons older than five years globally. New disease burden estimates from newly deployed molecular diagnostic assays with increased sensitivity suggest that Shigella-associated morbidity may be much greater than previous disease estimates from culture-based methods. Primary prevention of this disease should be based on universal provision of potable water and sanitation methods and improved personal and food hygiene. However, an efficacious and low-cost vaccine would complement and accelerate disease reduction while waiting for universal access to water, sanitation, and hygiene improvements. This review article provides a landscape of Shigella vaccine development efforts. No vaccine is yet available, but human and animal challenge–rechallenge trials with virulent Shigella as well as observational studies in Shigella-endemic areas have shown that the incidence of disease decreases following Shigella infection, pointing to biological feasibility of a vaccine. Immunity to Shigella appears to be strain-specific, so a vaccine that covers the most commonly detected strains (i.e., S. flexneri 2a, 3a, 6, and S. sonnei) or a vaccine using cross-species conserved antigens would likely be most effective. Vaccine development and testing may be accelerated by use of animal models, such as the guinea pig keratoconjunctivitis or murine pneumonia models. Because there is no correlate of protection, however, human studies will be necessary to evaluate vaccine efficacy prior to deployment. A diversity of Shigella vaccine constructs are under development, including live attenuated, formalin-killed whole-cell, glycoconjugate, subunit, and novel antigen vaccines (e.g., Type III secretion system and outer membrane proteins).

• Publisher: Elsevier Ltd,Elsevier Limited
• Subject: Adjuvants / Animal models / Animals / antigens / Bacteria / Biomedical Research - trends / burden of disease / children / Clinical Trials as Topic / Combined vaccines / Diarrhea / Diarrhea - microbiology / Diarrhea - prevention & control / Diarrheal disease / disease incidence / Disease Models, Animal / disease prevention / Drinking water / Dysentery / Dysentery, Bacillary - prevention & control / elderly / Enteric vaccines / Food sanitation / Genes / Gram-negative bacteria / guinea pigs / Humans / hygiene / immunity / Impact assessment / keratoconjunctivitis / mice / morbidity / Mortality / Observational studies / outer membrane proteins / Pathogens / pneumonia / R&D / Research & development / Sanitation / Shigella / Shigella Vaccines - therapeutic use / type III secretion system / vaccine development / Vaccines / Vaccines, Conjugate - therapeutic use / Vaccines, Subunit - therapeutic use / virulence / Waterborne diseases