Priming of CD8+ CTL effector cells in mice by immunization with a stress protein–influenza virus nucleoprotein fusion molecule
| Autor: | Cor Turnnir, Mizzen Lee, Lawrence S. D. Anthony, Huacheng Wu, Leslie J. Boux, Heather Sweet |
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| Rok vydání: | 1999 |
| Předmět: |
Cellular immunity
Orthomyxoviridae Priming (immunology) chemical and pharmacologic phenomena CD8-Positive T-Lymphocytes T-Lymphocytes Regulatory Immunophenotyping Fusion gene Mice Animals Heat-Shock Proteins General Veterinary General Immunology and Microbiology biology Public Health Environmental and Occupational Health biology.organism_classification Fusion protein Virology Nucleoprotein Mice Inbred C57BL CTL Nucleoproteins Infectious Diseases Influenza virus nucleoprotein Molecular Medicine Female Immunization Viral Fusion Proteins T-Lymphocytes Cytotoxic |
| Zdroj: | Vaccine. 17:373-383 |
| ISSN: | 0264-410X |
| DOI: | 10.1016/s0264-410x(98)00199-6 |
| Popis: | Literature is accumulating which suggests the potential for stress proteins to form the basis of a novel vaccine technology. Immunization with mammalian tumor-derived stress proteins and their associated peptides promote anti-tumor immunity. Vaccination with HIV-1 p24 antigen fused to mycobacterial heat shock protein (Hsp) Hsp71 enhances p24-specific immunity, as measured by p24-specific antibody production and in vitro cell proliferation and cytokine induction. An ovalbumin-Hsp71 fusion protein primes ovalbumin-specific CTL activity and resistance to challenge with an ovalbumin-expressing tumor. We have extended these observations by using a mycobacterial Hsp65 fusion molecule to prime CTL specific for a viral antigen. Gene fusion constructs were generated from DNA encoding Mycobacterium bovis strain BCG Hsp65 and individual fragments of influenza virus nucleoprotein (NP) encompassing H-2Kd- and H-2Db-restricted CTL epitopes. The ability of these purified recombinant fusion proteins to prime NP-specific CTL was assessed in mice of appropriate H-2 haplotypes. We observed that adjuvant-free immunization with either fusion protein elicited significant CTL activity when administered at doses of 10-100 micrograms per mouse. An NP fusion protein made with glutathione-S-transferase failed to elicit NP-specific CTL, indicating that the phenomenon requires Hsp65 sequences. A single immunization with the Hsp65-NP fusion protein elicited CTL activity which persisted for a minimum of 4 months post-immunization, at which time it could be boosted by a second immunization. To our knowledge, this is the first report of a member of the Hsp60 family priming for antigen-specific CTL activity when employed as a fusion protein partner. |
| Databáze: | OpenAIRE |
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