Efforts to develop vaccines for prevention of acute diarrhea have been going on for more than 40 y with partial success. The myriad of pathogens, more than 20, that have been identified as a cause of acute diarrhea throughout the years pose a significant challenge for selecting and further developing the most relevant vaccine candidates. Based on pathogen distribution as identified in epidemiological studies performed mostly in low-resource countries, rotavirus, Cryptosporidium, Shigella, diarrheogenic E. coli and V. cholerae are predominant, and thus the main targets for vaccine development and implementation. Vaccination against norovirus is most relevant in middle/high-income countries and possibly in resource-deprived countries, pending a more precise characterization of disease impact. Only a few licensed vaccines are currently available, of which rotavirus vaccines have been the most outstanding in demonstrating a significant impact in a short time period. This is a comprehensive review, divided into 2 articles, of nearly 50 vaccine candidates against the most relevant viral and bacterial pathogens that cause acute gastroenteritis. In order to facilitate reading, sections for each pathogen are organized as follows: i) a discussion of the main epidemiological and pathogenic features; and ii) a discussion of vaccines based on their stage of development, moving from current licensed vaccines to vaccines in advanced stage of development (in phase IIb or III trials) to vaccines in early stages of clinical development (in phase I/II) or preclinical development in animal models. In this first article we discuss rotavirus, norovirus and Vibrio cholerae. In the following article we will discuss Shigella, Salmonella (non-typhoidal), diarrheogenic E. coli (enterotoxigenic and enterohemorragic), and Campylobacter jejuni.
Keywords: ALA, aminolevulenic acid; ASC, antibody secreting cell; Ace, accessory cholera enterotoxin; CT, cholera toxin; CT-A cholera toxin A subunit; CT-B cholera toxin B subunit; Cep, core encoded pilus; E. coli; ETEC; ETEC, enterotoxigenic E. coli; GEMS, global enteric multi-center study; HA/P, hemaglutinin protease; HBGA, histo-blood group antibodies; IS, intussusception; IgA, immunoglobulin A; IgG, immunoglobulin G; IgM, immunoglobulin M; LB, lower boundary; LLR, Lanzhou Lamb Rotavirus vaccine; LPS, lipopolysaccharide; MPL, monophosphoril lipid A; MSH, mannose-sensitive hemaglutinin pilus; REST, rotavirus efficacy and safety trial; RITARD; RR, relative risk, CI, confidence interval; RecA, recombinase A; SAES, serious adverse events; SRSV, small round virus, ORF, open reading frame; STEC; STEC, shigatoxin producing E. coli; TCP, toxin co-regulated pilus; V. cholerae; VA1.3, vaccine attempt 1.3; VLP, virus like particle; VLPs, virus like particles, VRPs, virus replicon particles; VP, viral proteins; WHO, World Health Organization; Zot, zonula occludens toxin; acute diarrhea; campylobacter; enteric pathogens; gastroenteritis; norovirus; removable intestinal tie-adult rabbit diarrhea; rotavirus; salmonella; shigella; vaccines.