Abstract
Shigellosis remains a major public health problem around the world; it is one of the leading causes of diarrhoeal disease in low- and middle-income countries, particularly in young children. The increasing reports of Shigella cases associated with anti-microbial resistance are an additional element of concern. Currently, there are no licensed vaccines widely available against Shigella, but several vaccine candidates are in development. It has been demonstrated that the incidence of disease decreases following a prior Shigella infection and that serum and mucosal antibody responses are predominantly directed against the serotype-specific Shigella O-antigen portion of lipopolysaccharide membrane molecules. Many Shigella vaccine candidates are indeed O-antigen-based. Here we present the journey towards the development of a potential low-cost four-component Shigella vaccine, eliciting broad protection against the most prevalent Shigella serotypes, that makes use of the GMMA (Generalized Modules for Membrane Antigens) technology, a novel platform based on bacterial outer membranes for delivery of the O-antigen to the immune system.
Highlights
Shigella spp. are a leading cause of diarrhoeal mortality among all ages worldwide [1–3]
If the cross protection observed in animals can be extrapolated to humans, multivalent vaccines against S. sonnei and the most common circulating S. flexneri serotypes are expected to achieve approximately 65% coverage, which could further increase to over 85% depending upon the degree of cross-protection elicited against S. flexneri strains not contained in the vaccine [3]
We present the journey towards the development of a potential low-cost fourcomponent Shigella vaccine, eliciting broad protection against the most prevalent Shigella serotypes, that makes use of the GMMA (Generalized Modules for Membrane Antigens) technology, a novel platform based on bacterial outer membranes for delivery of the OAg to the immune system [29,30]
Summary
Shigella spp. are a leading cause of diarrhoeal mortality among all ages worldwide [1–3]. Recent estimates report approximately 270 million diarrhoea episodes due to Shigella, with around 212,000 deaths among all ages per year, of which 64,000 are in children under 5 years Among these deaths, 90% occur in low- and-middle-income countries (LMICs) [1]. Live oral vaccines [16–19] and O-polysaccharide-protein conjugate vaccines [20,21] that have conferred protection in randomized controlled field trials have corroborated the importance of immune responses to Shigella OAg. The prevalence of Shigella serotypes varies by country economic status and between geographical regions and changes over time even within one region. We present the journey towards the development of a potential low-cost fourcomponent Shigella vaccine, eliciting broad protection against the most prevalent Shigella serotypes, that makes use of the GMMA (Generalized Modules for Membrane Antigens) technology, a novel platform based on bacterial outer membranes for delivery of the OAg to the immune system [29,30]
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