ABSTRACT
Tumor necrosis factor (TNF) is involved in host resistance to several intracellular pathogens. Although the critical role of TNF receptor (TNFR)p55 in Leishmania (Leishmania) major infection has been demonstrated, the impact of TNFRp55 deficiency on L. (L.) amazonensis infection has not been explored. L. (L.) amazonensis-infected TNFRp55(-/-) mice failed to resolve lesions, whereas C57BL/6 wild-type mice completely healed. The susceptibility of the TNFRp55(-/-) mice was characterized by higher lesion size and histopathological damage in comparison with the wild-type mice. A marked increased of the splenic index was observed in the TNFRp55(-/-) mice after 15 weeks infection. These results show that in the absence of TNFRp55, L. (L.) amazonensis-infected knockout mice fail to resolve lesions, whereas wild-type mice completely heal.
Subject(s)
Genetic Predisposition to Disease , Leishmania mexicana/immunology , Leishmaniasis, Cutaneous/genetics , Receptors, Tumor Necrosis Factor, Type I/deficiency , Tumor Necrosis Factor Decoy Receptors/deficiency , Animals , Leishmaniasis, Cutaneous/pathology , Mice, Inbred C57BL , Mice, KnockoutABSTRACT
BACKGROUND/PURPOSE: A proper adjuvant has a relevant role in vaccine formulations to generate an effective immune response. In this study, total Leishmania antigen (TLA) formulated with Montanide ISA 763 or R848 as adjuvants were evaluated as a first generation Leishmania vaccine in a murine model. METHODS: Immunization protocols were tested in BALB/c mice with a subcutaneous prime/boost regimen with an interval of 3 weeks. Mice immunized with unadjuvanted TLA and phosphate-buffered saline (PBS) served as control groups. On Day 21 and Day 36 of the protocol, we evaluated the humoral immune response induced by each formulation. Fifteen days after the boost, the immunized mice were challenged with 1 × 10(5) promastigotes of Leishmania (Leishmania) amazonensis in the right footpad (RFP). The progress of the infection was followed for 10 weeks; at the end of this period, histopathological studies were performed in the RFP. RESULTS: Vaccines formulated with Montanide ISA 763 generated an increase in the production of immunoglobulin G (IgG; p < 0.05) compared with the control group. There were no statistically significant differences in IgG1 production between the study groups. However, immunization with TLA-Montanide ISA 763 resulted in an increase in IgG2a compared to the unadjuvanted control (p < 0.001). Also noteworthy was the fact that a significant reduction in swelling and histopathological damage of the RFP was recorded with the Montanide ISA 763 formulation. CONCLUSION: We conclude that the immunization of BALB/c mice with a vaccine formulated with TLA and Montanide ISA 763 generated a protective immune response against L. (L.) amazonensis, characterized by an intense production of IgG2a.
Subject(s)
Adjuvants, Immunologic/administration & dosage , Antigens, Protozoan/immunology , Leishmania mexicana/immunology , Leishmaniasis Vaccines/immunology , Leishmaniasis, Cutaneous/prevention & control , Oils/administration & dosage , Animals , Antibodies, Protozoan/blood , Antigens, Protozoan/administration & dosage , Antigens, Protozoan/isolation & purification , Disease Models, Animal , Female , Immunization Schedule , Immunoglobulin G/blood , Injections, Subcutaneous , Leishmaniasis Vaccines/administration & dosage , Leishmaniasis Vaccines/isolation & purification , Leishmaniasis, Cutaneous/immunology , Mice, Inbred BALB CABSTRACT
In pursuit of better influenza vaccines, many strategies are being studied worldwide. An attractive alternative is the generation of a broadly cross-reactive vaccine based on the induction of cytotoxic T-lymphocytes (CTL) directed against conserved internal antigens of influenza A virus. The feasibility of this approach using recombinant viral vectors has recently been demonstrated in mice and humans by several research groups. However, similar results might also be achieved through immunization with viral proteins expressed in a prokaryotic system formulated with the appropriate adjuvants and delivery systems. This approach would be much simpler and less expensive. Recent results from several laboratories seem to confirm this is as a valid option to be considered.
Subject(s)
Influenza Vaccines/immunology , Influenza, Human/prevention & control , T-Lymphocytes, Cytotoxic/immunology , Adjuvants, Immunologic/pharmacology , Animals , Cross Reactions , Disease Models, Animal , Gene Transfer Techniques , Genetic Vectors , Humans , Influenza A virus/immunology , Vaccination , Vaccines, Synthetic/immunology , Vaccines, Synthetic/virology , Viral Proteins/immunologyABSTRACT
In this work, we assessed the efficacy of an experimental intranasal vaccine against urinary-tract infections. The vaccine contained a recombinant truncated FimH (rFimHt) adhesin plus CpG oligodeoxynucleotides. The efficacy of the vaccine was compared with that of an intramuscular vaccine that was formulated with the same immunogen plus Freund's adjuvant. Our results show that serum immunoglobulin G titers of vaccinated animals were similarly enhanced in both cases. However, the intranasal vaccine elicited higher vaginal-wash-specific immunoglobulin A titers against rFimHt than the intramuscular route. Both vaccines reduced the in vivo colonization of the bladder by uropathogenic Escherichia coli more than 100-fold in a murine cystitis model. Our results indicate that a recombinant truncated FimH adhesin plus CpG oligodeoxynucleotides is a suitable immunogenic combination that can contribute to the development of a highly efficacious urinary tract infection vaccine.
