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.

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