Shigella Vaccines: The Continuing Unmet Challenge

Abstract

Shigellosis is a severe gastrointestinal disease that annually affects approximately 270 million individuals globally. It has particularly high morbidity and mortality in low-income regions; however, it is not confined to these regions and occurs in high-income nations when conditions allow. The ill effects of shigellosis are at their highest in children ages 2 to 5, with survivors often exhibiting impaired growth due to infection-induced malnutrition. The escalating threat of antibiotic resistance further amplifies shigellosis as a serious public health concern. This review explores Shigella pathology, with a primary focus on the status of Shigella vaccine candidates. These candidates include killed whole-cells, live attenuated organisms, LPS-based, and subunit vaccines. The strengths and weaknesses of each vaccination strategy are considered. The discussion includes potential Shigella immunogens, such as LPS, conserved T3SS proteins, outer membrane proteins, diverse animal models used in Shigella vaccine research, and innovative vaccine development approaches. Additionally, this review addresses ongoing challenges that necessitate action toward advancing effective Shigella prevention and control measures.

Vaccination with a Protective Ipa Protein-Containing Nanoemulsion Differentially Alters the Transcriptomic Profiles of Young and Elderly Mice following Shigella Infection

“…Shigella is an intracellular pathogen that causes severe diarrhea or dysentery, with 270 million cases globally each year resulting in approximately 212,000 deaths [ 1 ]. Shigella spp.…”

“…Shigella spp. include S. dysenteriae , S. flexneri , S. boydii , and S. sonnei , which are further divided into more than 50 serotypes based on O-antigen composition [ 1 ]. S. flexneri is a significant public health concern, particularly in low- and middle-income countries with poor sanitation and hygiene practices [ 1 ].…”

“…include S. dysenteriae , S. flexneri , S. boydii , and S. sonnei , which are further divided into more than 50 serotypes based on O-antigen composition [ 1 ]. S. flexneri is a significant public health concern, particularly in low- and middle-income countries with poor sanitation and hygiene practices [ 1 ]. Treatment of S. flexneri infections typically involves antibiotics, such as fluoroquinolones, β-lactams, and cephalosporins, but the emergence of antibiotic-resistant strains has become a growing problem [ 2 , 3 ].…”

“…The mouse pulmonary model for Shigella research is efficient, offering valuable insights into Shigella pathogenesis and host responses [ 1 , 11 ]. While mouse intestinal models exist, it is crucial to acknowledge their limited commercial availability, especially for aging studies [ 12 ].…”

“…While mouse intestinal models exist, it is crucial to acknowledge their limited commercial availability, especially for aging studies [ 12 ]. In contrast, the mouse Shigella pulmonary challenge model remains widely used and accessible, serving as a vital tool for studying infection dynamics and evaluating vaccine efficacy [ 1 , 13 ]. This model facilitates controlled investigations of mucosal immune responses and enables early-stage assessment of candidate vaccines’ effectiveness in preventing Shigella infections [ 1 , 13 ].…”