Rapid clearance of a recombinant Salmonella vaccine carrier prevents enhanced antigen-specific CD8 T-cell responses after oral boost immunizations

• Published in: Microbes and infection Vol. 7; no. 5; pp. 860 - 866
• Main Authors: Domènech, Victòria E. Sevil, Panthel, Klaus, Meinel, Katrin M., Rüssmann, Holger
• Format: Journal Article
• Language: English
• Published: Lausanne Elsevier SAS 01.05.2005; Amsterdam Elsevier; Paris
• Subjects: Administration, Oral; Animals; Antigens, Bacterial - immunology; Antivector immunity; Applied microbiology; Bacterial vaccine carrier; Bacterial Vaccines - administration & dosage; Bacterial Vaccines - immunology; Bacteriology; Biological and medical sciences; Boost immunization; CD8 T cell; CD8-Positive T-Lymphocytes - physiology; Female; Fundamental and applied biological sciences. Psychology; Genetic Vectors; Heterologous antigen; Immunization, Secondary; Intestines - microbiology; Listeria monocytogenes; Listeria monocytogenes - immunology; Lymph Nodes - microbiology; Mice; Mice, Inbred BALB C; Microbiology; Miscellaneous; Salmonella enterica; Salmonella enterica serovar Typhimurium; Salmonella typhimurium; Spleen - microbiology; Time Factors; Type III secretion system; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Vaccines, Synthetic - administration & dosage; Vaccines, Synthetic - immunology; Yersinia; CD8 T cell; YopE; Bacterial vaccine carrier; SCV; TTSS; Salmonella enterica serovar Typhimurium; MHC; Type III secretion system; Elispot; IFN-γ; Heterologous antigen; CFU; APC; Boost immunization; Antivector immunity; Immunization; Cellular immunity; Vaccine; Clearance; CDS T cell; Salmonella typhimurium; T-Lymphocyte; Bacteria; Enterobacteriaceae
• ISSN: 1286-4579; 1769-714X
• DOI: 10.1016/j.micinf.2005.02.007

The type III secretion system of Salmonella enterica serovar Typhimurium can be used to target heterologous antigens directly into the cytosol of antigen-presenting cells. Our laboratory has previously reported that the single oral immunization of mice with a recombinant Salmonella strain expressing the translocated Yersinia outer protein E fused to the immunodominant antigen p60 from Listeria monocytogenes results in the efficient induction of p60-specific CD8 T cells and confers protection against a lethal wild-type Listeria challenge infection. In the present study, we investigated whether these antigen-specific cytotoxic T lymphocytes induced by the prime immunization contribute to a more rapid clearance of the vaccine carrier after subsequent boost immunizations and whether oral boost immunizations lead to an augmented p60-specific CD8 T-cell response. We found that the ability of recombinant Salmonella strains to colonize the intestine, mesenteric lymph nodes, and spleen was markedly impaired after boost immunizations but that this effect was independent of existing CD8 T cells reactive with p60 217–225. A significant elevation of antigen-specific CD8 T cells could not be detected by enzyme-linked immunospot assay after the second or the third oral immunization, possibly due to the rapid clearance of the bacterial vaccine carrier from lymphatic organs.