M Cell DNA Vaccination for CTL Immunity to HIV
| Autor: | Xinhai Wang, Asmahan Haddad, Mohamed T. Shata, David M. Hone, David W. Pascual |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Cytotoxicity
Immunologic Male Pore Forming Cytotoxic Proteins Cellular immunity viruses Immunology Dose-Response Relationship Immunologic HIV Infections Vaccinia virus Lymphocyte Activation DNA vaccination Interferon-gamma Mice Peyer's Patches chemistry.chemical_compound Viral Envelope Proteins Immunity Vaccines DNA Animals Immunology and Allergy Immunity Mucosal Administration Intranasal Immunization Schedule Microfold cell AIDS Vaccines Mice Knockout Mice Inbred BALB C Membrane Glycoproteins biology Perforin virus diseases Virology CTL chemistry Naked DNA DNA Viral HIV-1 biology.protein Capsid Proteins Female Vaccinia T-Lymphocytes Cytotoxic |
| Zdroj: | The Journal of Immunology. 171:4717-4725 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.171.9.4717 |
| Popis: | To facilitate invasion, reovirus has evolved to attach to M cells, a specialized epithelium residing within the follicle-associated epithelium that covers mucosal inductive tissues. Thus, we questioned adapting reovirus protein σ1 to ferry DNA vaccines to the mucosa to immunize against HIV. Three expression plasmids encoding HIV(Ba-L) gp160, cytoplasmic gp140, and secreted gp140 were tested in mice as protein σ1-poly-l-lysine-DNA complexes (formulated vaccine) via the intranasal route. Evaluation of cell-mediated immunity showed that the formulated gp160 DNA vaccine was more effective for stimulating envelope (Env)-specific CTL responses in lungs, lower respiratory lymph nodes (LN), cervical LN, submaxillary gland LN, and spleens. Three doses of vaccine were required for CTL responses, and intranasal naked DNA immunizations were ineffective. The greatest CTL activity was observed between weeks 8 and 10 for gp160-vaccinated mice, and activity remained detectable by week 16. These Env-specific CTL responses were perforin dependent in peripheral tissues, but mostly Fas dependent in the lungs. These Env-specific CTLs also produced IFN-γ. Mice vaccinated with the formulated gp160 DNA vaccine showed potent antiviral immunity against vaccinia virus-env replication in ovaries. Thus, compared with live vectors, protein σ1-mediated DNA delivery represents an alternative mucosal formulation for inducing cellular immunity against HIV-1. |
| Databáze: | OpenAIRE |
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