Status of vaccine research and development for Shigella

Abstract

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).

Shigella Vaccine Development: Finding the Path of Least Resistance

“…Furthermore, vaccines which appear immunogenic but somewhat reactogenic in volunteers from high-resource settings have been well-tolerated but overattenuated when given to adults and children in developing countries (33,34). Reviews of the pitfalls and successes of Shigella vaccine candidates under development have been published (8,(35)(36)(37). Nonetheless, there is hope that newer generations of these constructs can be both well-tolerated and immunogenic.…”

A tale of two bacterial enteropathogens and one multivalent vaccine

“…Although many Shigella vaccine strategies have been pursued (reviewed in Ashkenazi & Cohen, ; Barry et al, ; Levine et al, ; Mani, Wierzba, & Walker, ), the current leading approaches include the following: (a) parenteral vaccines that deliver chemically purified or synthetic Shigella OPS antigens as conjugates to carrier proteins, genetic bioconjugates (Riddle et al, ) or as general outer membrane vesicles derived from Shigella serotypes (Launay et al, ), or; (b) live attenuated vaccine strains administered as live oral vaccines.…”

Oral immunization with LacVax® OmpA induces protective immune response against Shigella flexneri 2a ATCC 12022 in a murine model

“…Every year, around 600,000 deaths occur due to shigellosis, of which, 500,000 cases are reported amongst military personnel and travelers from industrialized countries. The major factors responsible for high incidences of shigellosis in developing countries are lack of clean water, poor sanitation and malnutrition [3]. While public health strategies to reduce exposure and transmission are effective, their establishment in many developing countries, especially in the context of conflict or mass displacement of susceptible person remains challenging [4].…”

“…Despite of numerous efforts in https://doi.org/10.1016/j.vaccine.2019.04.053 0264-410X/Ó 2019 Elsevier Ltd. All rights reserved. the past few decades, at present there is no licensed vaccine available in the market while several other candidate vaccines are currently at different pre-clinical and clinical stages [3].…”