Vaccines against gastroenteritis, current progress and challenges

Abstract

Enteric viral and bacterial infections continue to be a leading cause of mortality and morbidity in young children in low-income and middle-income countries, the elderly, and immunocompromised individuals. Vaccines are considered an effective and practical preventive approach against the predominantly fecal-to-oral transmitted gastroenteritis particularly in the resource-limited countries or regions where implementation of sanitation systems and supply of safe drinking water are not quickly achievable. While vaccines are available for a few enteric pathogens including rotavirus and cholera, there are no vaccines licensed for many other enteric viral and bacterial pathogens. Challenges in enteric vaccine development include immunological heterogeneity among pathogen strains or isolates, a lack of animal challenge models to evaluate vaccine candidacy, undefined host immune correlates to protection, and a low protective efficacy among young children in endemic regions. In this article, we briefly updated the progress and challenges in vaccines and vaccine development for the leading enteric viral and bacterial pathogens including rotavirus, human calicivirus, Shigella, enterotoxigenic Escherichia coli (ETEC), cholera, nontyphoidal Salmonella, and Campylobacter, and introduced a novel epitope- and structure-based vaccinology platform known as MEFA (multiepitope fusion antigen) and the application of MEFA for developing broadly protective multivalent vaccines against heterogenous pathogens.

Keywords: Campylobacter; Shigella; Vibrio cholerae; Enteric diseases; enterotoxigenic Escherichia coli (ETEC); multiepitope fusion antigen (MEFA); nontyphoidal Salmonella; norovirus; rotavirus; vaccinology.

Figure 1.

A scheme to illustrate vaccinology evolution. From conventional vaccinology to reverse vaccinology and further to structural vaccinology, leading from whole-cell vaccines, to subunit vaccines and then structural epitope vaccines.

Figure 2.

MEFA vaccinology applies a backbone immunogen to present neutralizing epitopes of virulence determinants from multiple heterogeneous strains, by substituting backbone surface exposed but less immunogenic backbone epitopes with foreign epitopes, and to mimic foreign epitope native antigenicity assisted with protein modeling and molecule dynamics simulation.