Reduced pathology following infection with transgenic Leishmania major expressing murine CD40 ligand
| Autor: | Ann E. Field, David M. Mosser, Sean M. Conrad, Sagie Wagage |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Protozoan Vaccines
Mice Inbred BALB C biology Organisms Genetically Modified Immunogenicity Transgene Immunology CD40 Ligand Vaccination Kinetoplastida Virulence biology.organism_classification Leishmania Microbiology Virology Mice Infectious Diseases Immune system Antigen Animals Parasitology Leishmania major CD40 Antigens Fungal and Parasitic Infections |
| Zdroj: | Infection and immunity. 75(6) |
| ISSN: | 0019-9567 |
| Popis: | Leishmanization is the inoculation of liveLeishmaniainto the host to vaccinate against subsequent infections. This approach has been largely discontinued due to safety concerns. We have previously shown that combining CD40 ligand (CD40L) withLeishmaniaantigen preferentially induces a type 1 immune response and provides some protection to vaccinated mice (G. Chen, P. A. Darrah, and D. M. Mosser, Infect. Immun.69:3255-3263, 2001). In the present study, we developed transgenicL. majororganisms which express and secrete the extracellular portion of CD40L (L. majorCD40LE). We hypothesized that these organisms would be less virulent but more immunogenic than wild-type organisms and therefore be more effective at leishmanization. Transgenic parasites expressing CD40L mRNA and protein were developed. BALB/c mice infected with these parasites developed significantly smaller lesions containing fewer parasites than animals infected with wild-type organisms. Infection of resistant C57BL/6 mice with low doses of transgenic parasites induced a significant amount of protection against subsequent high-dose infection with wild-type organisms. These results demonstrate that transgenic organisms expressing CD40L are less virulent than wild-type organisms while retaining full immunogenicity. |
| Databáze: | OpenAIRE |
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