Typhoid fever & vaccine development: a partially answered question.

Typhoid fever is a systemic disease caused by the human specific Gram-negative pathogen Salmonella enterica serovar Typhi (S. Typhi). The extra-intestinal infections caused by Salmonella are very fatal. The incidence of typhoid fever remains very high in impoverished areas and the emergence of multidrug resistance has made the situation worse. To combat and to reduce the morbidity and mortality caused by typhoid fever, many preventive measures and strategies have been employed, the most important being vaccination. In recent years, many Salmonella vaccines have been developed including live attenuated as well as DNA vaccines and their clinical trials have shown encouraging results. But with the increasing antibiotic resistance, the development of potent vaccine candidate for typhoid fever is a need of the hour. This review discusses the latest trends in the typhoid vaccine development and the clinical trials which are underway.

Adjuvant effect of DEAE-dextran and tetanus toxoid on whole cell heat inactivated phenol preserved typhoid vaccine.

Active mouse protection test (AMPT) and enzyme linked immunosorbent assay (ELISA) were used to determine the immunogenicity of whole cell typhoid vaccine when administered in conjunction with either tetanus toxoid (TT) or DEAE-Dextran (DD). Immunization of mice with whole cell typhoid vaccine showed enhanced potency either when administered in conjunction with TT or DD and values were statistically significant (p < 0.05) in comparison to conventional or standard typhoid vaccines. For ELISA, the mice were immunized with 2 different schedules, one in which a single dose of 0.25 ml subcutaneously (s/c) was administered and in another two doses of 0.25 ml each s/c, 14 days apart. In case of single dose schedule of immunization D vaccine (Whole cell typhoid + 5 mg/ml DD) showed significant increase of immune response (3.201 log10) as compared to plain vaccine (2.550 log10). Two dose schedule further increased the titres to 3.856 log10. DD adjuvanted vaccine showed higher potency by AMPT as compared to the TT adjuvanted vaccine or plain vaccine. The present study clearly demonstrates that a single dose of 0.25 ml which is equivalent to half of the conventionally used single human dose of typhoid vaccine adjuvanted with DD can significantly improve the immunogenicity of the vaccine.

[Anti-typhoid vaccines]. / Vaccins antityphiques.

There are three commercially available vaccines against typhoid fever: parenteral inactivated whole cell vaccine, oral live attenuated (strain ty21a), parenteral polysaccharide vaccine (capsular antigen-Vi). Their protective efficacy is 50 to 88% (inactivated vaccine), 50 to 96% (live attenuated vaccine) and 75 to 80% (polysaccharide vaccine). The frequency of notable adverse reactions with the inactivated vaccine justifies the use of the new vaccines.

A review of the current status of enteric vaccines.

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.

Capacidad fagocítica de las células del exudado peritoneal de ratones inmunizados con una preparación ribosomal de Salmonella Typhi Ty2 / Phagocytic capacity of exudate peritoneal cells from mice immunized with Salmonella typhi Ty2 ribosomal fraction

Se comparó la capacidad fagocítica de células ael exudado peritoneal (CEP) de ratones CFW inmunizados con una preparación ribosomal de Salmonella typhi Ty2, con la de ratones protegidos con una vacuna de bacterias inactivadas por calor, ambas en relación con lo obtenido en animales testigo, no inmunizados. Los ribosomas se administraron subcutáneamente en una dosis inicial de 100 µg de ARN y se dio un refuerzo igual a los 14 días, ambos con adyuvantes incompleto de Freund (AIF). Los ratones inmunizados con vacuna de células muertas, recibieron una sola dosis subcutánea con 16***6 bacterias en AIF. Al cabo de 7, 11, 14, 18, 22, 25, y 31 días se indujeron y extrajeron las CEP de los animales de cada grupo e individualmente se cultivaron in vitro junto con S. Typhi Ty2 virulento no opsonizado en relación células-bacterias 1:200. La sobrevida de las bacterias fagocitadas se determinó a las 24 horas de cultivo: las CEP se romperon y por cuenta viable se enumeraron las bacterias no digeridas. Los resultados indican que las CEP de los inmunizados eliminan bacterias con mayor eficiencia que las de testigos. También se demostró que la eficiencia bactericida fue significativamente mayor (P máxima de 0.005) para las CEP de los ratones tratados con la fracción ribosomal que las CEP de los animales vacunados con bacterias intactas no viables. Fiebre tifoidea; vacuna ribosomal; inmunidad a Salmonella; Salmonella typi; fagocitosis por células peritoneales