A Nasal Interleukin-12 DNA Vaccine CoexpressingYersinia pestisF1-V Fusion Protein Confers Protection against Pneumonic Plague
| Autor: | Catharine M. Bosio, Massimo Maddaloni, Todd Becker, David W. Pascual, Xinghong Yang, Teri Hoyt, Sarah Golden, Hitoki Yamanaka, Kathryn Crist |
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| Rok vydání: | 2008 |
| Předmět: |
Pore Forming Cytotoxic Proteins
Pneumonic plague Immunology Immunization Secondary Yersinia Microbiology Bubonic plague Immunoglobulin G DNA vaccination Mice Bacterial Proteins Immunity Vaccines DNA medicine Animals Lymphocytes Immunity Mucosal Administration Intranasal Antigens Bacterial Mice Inbred BALB C Plague Plague Vaccine biology biology.organism_classification medicine.disease Antibodies Bacterial Interleukin-12 Survival Analysis Virology Immunoglobulin A Infectious Diseases Yersinia pestis Microbial Immunity and Vaccines biology.protein Cytokines Plague vaccine Female Parasitology Spleen Plasmids |
| Zdroj: | Infection and Immunity. 76:4564-4573 |
| ISSN: | 1098-5522 0019-9567 |
| DOI: | 10.1128/iai.00581-08 |
| Popis: | Previous studies have shown that mucosal application of interleukin-12 (IL-12) can stimulate elevated secretory immunoglobulin A (IgA) responses. Since possible exposure to plague is viaYersinia pestis-laden aerosols that results in pneumonic plague, arming both the mucosal and systemic immune systems may offer an added benefit for protective immunity. Two bicistronic plasmids were constructed that encoded the protective plague epitopes, capsular antigen (F1-Ag) and virulence antigen (V-Ag) as a F1-V fusion protein but differed in the amounts of IL-12 produced. When applied nasally, serum IgG and mucosal IgA anti-F1-Ag and anti-V-Ag titers were detectable beginning at week 6 after three weekly doses, and recombinant F1-Ag boosts were required to elevate the F1-Ag-specific antibody (Ab) titers. Following pneumonic challenge, the best efficacy was obtained in mice primed with IL-12(Low)/F1-V vaccine with 80% survival compared to mice immunized with IL-12(Low)/F1, IL-12(Low)/V, or IL-12(Low) vector DNA vaccines. Improved expression of IL-12 resulted in lost efficacy when using the IL-12(High)/F1-V DNA vaccine. Despite differences in the amount of IL-12 produced by the two F1-V DNA vaccines, Ab responses and Th cell responses to F1- and V-Ags were similar. These results show that IL-12 can be used as a molecular adjuvant to enhance protective immunity against pneumonic plague, but in a dose-dependent fashion. |
| Databáze: | OpenAIRE |
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