Cellular and humoral immunity are synergistic in protection against types A and B Francisella tularensis
| Autor: | Dennis L. Kasper, LeeAnn T. Blalock, Jessica T. Pinkham, J. Wayne Conlan, Jillian G. Lynch, Robin A. Ross, Shite Sebastian, Barbara Reinap |
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| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Male
Cellular immunity Injections Intradermal combination vaccination Vaccines Attenuated Article Microbiology Tularemia Mice protective immunity Immunity medicine Animals Lung Francisella tularensis Immunity Cellular Mice Inbred BALB C Attenuated vaccine General Veterinary General Immunology and Microbiology biology Public Health Environmental and Occupational Health biology.organism_classification medicine.disease Virology Vaccination Bacterial vaccine Infectious Diseases Liver francisella tularensis Antibody Formation Bacterial Vaccines Humoral immunity Molecular Medicine |
| Popis: | Herein we report studies with a novel combination vaccine that, when administered to mice, conferred protection against highly virulent strains of Francisella tularensis by stimulating both arms of the immune system. Our earlier studies with Ft.LVS::wbtA, an O-polysaccharide (OPS)-negative mutant derived from the available live vaccine strain of F. tularensis (Ft.LVS), elucidated the role of antibodies to the OPS - a key virulence determinant - in protection against virulent type A organisms. However, when expressed on the organism, the OPS enhances virulence. In contrast, in purified form, the OPS is completely benign. We hypothesized that a novel combination vaccine containing both a component that induces humoral immunity and a component that induces cellular immunity to this intracellular microbe would have an enhanced protective capacity over either component alone and would be much safer than the LVS vaccine. Thus we developed a combination vaccine containing both OPS (supplied in an OPS-tetanus toxoid glycoconjugate) to induce a humoral antibody response and strain Ft.LVS::wbtA (which is markedly attenuated by its lack of OPS) to induce a cell-mediated protective response. This vaccine protected mice against otherwise-lethal intranasal and intradermal challenge with wild-type F. tularensis strains Schu S4 (type A) and FSC 108 (type B). These results represent a significant advance in our understanding of immunity to F. tularensis and provide important insight into the development of a safer vaccine effective against infections caused by clinical type A and B strains of F. tularensis. |
| Databáze: | OpenAIRE |
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