A review of the current status of enteric vaccines

Abstract

Much progress has been made in developing vaccines against the most important enteric infections. Two new vaccines against typhoid fever (oral Ty21a and parenteral Vi polysaccharide) have been licensed in many countries. Newer, more sophisticated typhoid vaccines undergoing clinical testing include recombinant attenuated Salmonella typhi strains and Vi polysaccharide-carrier-protein conjugate vaccines. Two inactivated oral cholera vaccines, consisting of inactivated Vibrio cholerae O1 bacteria alone or in combination with B subunit of cholera toxin, each conferred 50-53% protection over three years in a field trial in Bangladesh where subjects were immunized with a three-dose regimen. An engineered live oral cholera vaccine, strain CVD 103-HgR, has been shown in extensive clinical trials to be well tolerated by children and adults in less developed countries and highly immunogenic following administration of just a single oral dose; a large-scale field trial of the efficacy of this vaccine is underway. In experimental challenge studies in volunteers, a single dose of CVD 103-HgR confers significant protection against challenge with wild-type V. cholerae O1 of either classical or El Tor biotype and either Inaba or Ogawa serotype. Several candidate vaccines against Shigella and enterotoxigenic Escherichia coli are in clinical trials. A multivalent rotavirus vaccine (rhesus reassortant vaccine) is undergoing extensive field testing in developed and less developed countries.

PIP: The development of safe, effective vaccines to prevent diseases due to rotavirus, enterotoxigenic Escherichia coli, enteropathogenic E. coli, Shigella, and Vibrio cholerae O1 would markedly reduce the burden of diarrheal diseases in Third World countries. This review concentrates on vaccines that have already been licensed, that have been evaluated in controlled trials of efficacy, or that have entered clinical trials to assess their safety and immunogenicity. Two new vaccines against typhoid fever have been licensed. Newer, more sophisticated typhoid vaccines undergoing clinical testing include recombinant attenuated Salmonella typhi strains and Vi polysaccharide-carrier-protein conjugate vaccines. Inactivated oral cholera vaccines consisting of inactivated Vibrio cholerae O1 bacteria alone or in combination with B subunit of cholera toxin conferred 50-53% protection in a field trial in Bangladesh. An engineered live oral cholera vaccine, strain CVD 103-HgR, has been shown in extensive clinical trials to be well tolerated and highly immunogenic after a single oral dose. In experimental challenge studies, a single dose of CVD 103-HgR conferred significant protection against challenge with wild-type V. cholerae O1. Several candidate vaccines against Shigella and enterotoxigenic E. coli are in clinical trials. Finally, a multivalent rotavirus vaccine (rhesus reassortant) is undergoing extensive field testing.