Vaccines against enteric diseases : is it the path that is difficult or the difficult that is the path ?

Intestinal infections, or diarrhea, are the second leading cause of pediatric infectious mortality. You'd think that this would make them a priority for vaccine development. However, this is not the case, with one exception: rotavirus vaccines. This is probably due to the limited number of serotypes, and above all to the existence of a market in Northern countries, enabling manufacturers to make a return on their investment. The same cannot be said for the other most prevalent enteric pathogens, such as Shigella, enterotoxigenic Escherichia coli (ETEC) and Cryptosporidium, whose multiplicity of species and serotypes, as well as their prevalence in the world's poorest countries, currently make the development of an anti-diarrhoea vaccine illusory, even if tourists, NGO staff and military personnel on operations could benefit from it. The subject is complicated by the current lack of consensus on the optimal design of candidate vaccines and their ideal mode of administration: oral vaccine stimulating a predominantly mucosal response versus parenteral, often particulate, stimulating a predominantly systemic response. A highly complex dilemma emerges from this duality: conventional parenteral conjugate vaccines (polyoside-protein carrier) provide poor protection for very young children. Conversely, the immunogenicity of oral vaccines is significantly diminished by a newly-recognized entity in highly endemic regions, pediatric environmental enteropathy, which considerably reduces the capacity for colonization, and hence for uptake, of these vaccines. It's a tough road ahead...