RESUMO
Salmonella enterica is a facultative anaerobic bacteria, whose ability to colonize antigen-presenting cells (APCs) such as dendritic cells and macrophages, has allowed its successful use as an alive, attenuated bacterial vector for vaccination. Salmonella enterica elicits efficient cellular, humoral and mucosal immune responses, against heterologous antigens including viruses, parasites, other bacterial species and tumor-associated antigens, since it is capable of delivering these antigens to cells of the immune system. The extracellular expression of heterologous antigens on the surface of Salmonella enterica via its type I, III and V secretion systems, and their delivery into infected cells is essential for its stimulation of immune responses against these antigens. Moreover, Salmonella enterica is a promising therapeutic agent against cancer, as demonstrated by reports of pre-clinical and clinical studies indicating that, after systemic administration, Salmonella enterica preferentially localizes in solid tumors and metastases as compared to normal tissues. In this review, we focus on novel prophylactic and therapeutic anti-cancer approaches using Salmonella enterica as a delivery system of heterologous molecules with the aim of inhibiting tumor growth.
Assuntos
Antígenos Heterófilos/imunologia , Antígenos de Neoplasias/imunologia , Vacinas Anticâncer/uso terapêutico , Citocinas/uso terapêutico , Terapia Genética , Vetores Genéticos/uso terapêutico , Imunoterapia Ativa , Neoplasias/terapia , RNA Interferente Pequeno/uso terapêutico , Vacinas contra Salmonella/uso terapêutico , Salmonella enterica/imunologia , Animais , Apresentação de Antígeno , Antígenos Heterófilos/administração & dosagem , Antígenos Heterófilos/genética , Antígenos de Neoplasias/administração & dosagem , Antígenos de Neoplasias/genética , Sistemas de Secreção Bacterianos , Vacinas Anticâncer/administração & dosagem , Ensaios Clínicos como Assunto , Citocinas/administração & dosagem , Citocinas/genética , Vetores Genéticos/imunologia , Humanos , Camundongos , Neoplasias/imunologia , Neoplasias/microbiologia , Neoplasias/prevenção & controle , Neoplasias Experimentais/microbiologia , Neoplasias Experimentais/terapia , RNA Interferente Pequeno/administração & dosagem , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/uso terapêutico , Salmonella enterica/fisiologia , Terapêutica , Vacinas Vivas não Atenuadas , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
We report the oral vaccination of SWISS mice with an Aro attenuated Salmonella enterica var. Typhimurium vaccine strain expressing the 14-kDa Schistosoma mansoni antigen, Sm14. Bacterial adjuvants, including (i) Lactococcus lactis expressing interleukin-12 (IL-12) and (ii) Lactobacillus delbrueckii UFV-H2b20, were also employed in oral immunization assays. Detection assays to specific IgG and IgA anti-Sm14 antibodies were performed to evaluate humoral immune responses in vaccinated mice. An increase in specific IgG titers was observed; however, no IgA production was detected. The protection levels against schistosomiasis (34.9-49.5%) obtained with all experimental formulations in this work were very similar to values reported by previous studies, which used purified recombinant Sm14 for parenteral vaccination of mice. There was a slight reduction in hepatic granulomas of mice vaccinated with Salmonella. Oogram studies showed diminished numbers of S. mansoni eggs in the intestinal wall of vaccinated mice, but individual female worm fecundity did not seem to be affected by our immunization protocol.
Assuntos
Antígenos de Helmintos/imunologia , Proteínas de Helminto/imunologia , Proteínas de Membrana Transportadoras/imunologia , Vacinas contra Salmonella/uso terapêutico , Schistosoma mansoni/efeitos dos fármacos , Esquistossomose/imunologia , Animais , Antígenos de Helmintos/isolamento & purificação , Ensaio de Imunoadsorção Enzimática , Proteínas de Transporte de Ácido Graxo , Feminino , Proteínas de Helminto/biossíntese , Proteínas de Helminto/efeitos dos fármacos , Proteínas de Membrana Transportadoras/biossíntese , Proteínas de Membrana Transportadoras/efeitos dos fármacos , Camundongos , Plasmídeos/efeitos dos fármacos , Plasmídeos/genética , Esquistossomose/prevenção & controleRESUMO
The protection conferred by temperature-sensitive mutants of Salmonella enteritidis against different wild-type Salmonella serotypes was investigated. Oral immunization with the single temperature-sensitive mutant E/1/3 or with a temperature-sensitive thymine-requiring double mutant (E/1/3T) conferred: (i) significant protection against the homologous wild-type Salmonella strains; (ii) significant cross-protection toward high challenge doses of S. typhimurium. Significant antibody levels against homologous lipopolysaccharide and against homologous and heterologous protein antigens were detected in sera from immunized mice. Moreover, a wide range of protein antigens from different Salmonella O serotypes were recognized by sera from immunized animals. Besides, primed lymphocytes from E/1/3 immunized mice recognized Salmonella antigens from different serotypes. Taken together, these results indicate that temperature-sensitive mutants of S. enteritidis are good candidates for the construction of live vaccines against Salmonella.