Abstract
The global diarrheal disease burden for Shigella, enterotoxigenic Escherichia coli (ETEC), and Campylobacter is estimated to be 88M, 75M, and 75M cases annually, respectively. A vaccine against this target trio of enteric pathogens could address about one-third of diarrhea cases in children. All three of these pathogens contribute to growth stunting and have demonstrated increasing resistance to antimicrobial agents. Several combinations of antigens are now recognized that could be effective for inducing protective immunity against each of the three target pathogens in a single vaccine for oral administration or parenteral injection. The vaccine combinations proposed here would result in a final product consistent with the World Health Organization’s (WHO) preferred product characteristics for ETEC and Shigella vaccines, and improve the vaccine prospects for support from Gavi, the Vaccine Alliance, and widespread uptake by low- and middle-income countries’ (LMIC) public health stakeholders. Broadly protective antigens will enable multi-pathogen vaccines to be efficiently developed and cost-effective. This review describes how emerging discoveries for each pathogen component of the target trio could be used to make vaccines, which could help reduce a major cause of poor health, reduced cognitive development, lost economic productivity, and poverty in many parts of the world.
Highlights
The development of a vaccine against Shigella, a major cause of bacterial dysentery, was pursued in the early part of the 20th century, and in the 1960s, new approaches to develop genetically attenuated Shigella began [1]
With exceptions such as cholera and rotavirus, there are still no licensed vaccines against many enteric pathogens. This is true for Shigella and for the more newly recognized pathogens such as enterotoxigenic Escherichia coli (ETEC) and Campylobacter jejuni, which have been identified as major causes of enteric disease
ACE527, consisting of three ETEC strains expressing major CF and CS antigens, as well as the B subunit of labile toxin, was significantly protective in people when co-administered with a non-toxic double mutant of LT, double-mutant heat-labile toxin (dmLT), which acts as a mucosal adjuvant and an antigen [52]
Summary
The development of a vaccine against Shigella, a major cause of bacterial dysentery, was pursued in the early part of the 20th century, and in the 1960s, new approaches to develop genetically attenuated Shigella began [1]. With exceptions such as cholera and rotavirus, there are still no licensed vaccines against many enteric pathogens This is true for Shigella and for the more newly recognized pathogens such as enterotoxigenic Escherichia coli (ETEC) and Campylobacter jejuni, which have been identified as major causes of enteric disease. The major driver for enteric vaccine development has evolved from a primary focus on reducing mortality to factoring in reductions in acute and more longer-term morbidity, as well as socio-economic benefits. This approach will be more formally defined in value proposition documents that are under development for both Shigella and ETEC. This review article describes how emerging discoveries regarding each pathogen component of the target trio could be leveraged to make combined products that could help reduce a major cause of poor health, mortality, reduced growth and cognitive development, lost economic productivity, and poverty in many parts of the world
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