| Efficient generation of mucosal and systemic antigen-specific CD8+ T-cell responses following pulmonary DNA immunization. | |
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MedLine Citation:
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PMID: 20335249 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Although mucosal CD8(+) T-cell responses are important in combating mucosal infections, the generation of such immune responses by vaccination remains problematic. In the present study, we evaluated the ability of plasmid DNA to induce local and systemic antigen-specific CD8(+) T-cell responses after pulmonary administration. We show that the pulmonary delivery of plasmid DNA formulated with polyethyleneimine (PEI-DNA) induced robust systemic CD8(+) T-cell responses that were comparable in magnitude to those generated by intramuscular (i.m.) immunization. Most importantly, we observed that the pulmonary delivery of PEI-DNA elicited a 10-fold-greater antigen-specific CD8(+) T-cell response in lungs and draining lymph nodes of mice than that of i.m. immunization. The functional evaluation of these pulmonary CD8(+) T cells revealed that they produced type I cytokines, and pulmonary immunization with PEI-DNA induced lung-associated antigen-specific CD4(+) T cells that produced higher levels of interleukin-2 than those induced by i.m. immunization. Pulmonary PEI-DNA immunization also induced CD8(+) T-cell responses in the gut and vaginal mucosa. Finally, pulmonary, but not i.m., plasmid DNA vaccination protected mice from a lethal recombinant vaccinia virus challenge. These findings suggest that pulmonary PEI-DNA immunization might be a useful approach for immunizing against pulmonary pathogens and might also protect against infections initiated at other mucosal sites. |
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Authors:
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Maytal Bivas-Benita; Liat Bar; Geoffrey O Gillard; David R Kaufman; Nathaniel L Simmons; Avi-Hai Hovav; Norman L Letvin |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-03-24 |
Journal Detail:
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Title: Journal of virology Volume: 84 ISSN: 1098-5514 ISO Abbreviation: J. Virol. Publication Date: 2010 Jun |
Date Detail:
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Created Date: 2010-05-05 Completed Date: 2010-06-08 Revised Date: 2011-03-03 |
Medline Journal Info:
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Nlm Unique ID: 0113724 Medline TA: J Virol Country: United States |
Other Details:
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Languages: eng Pagination: 5764-74 Citation Subset: IM |
Affiliation:
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Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antigens CD8-Positive T-Lymphocytes / immunology* Cytokines / biosynthesis Drug Administration Routes Female Immunization / methods* Intestinal Mucosa Lung* / immunology Mice Mucous Membrane / immunology* Plasmids / administration & dosage*, immunology, therapeutic use T-Cell Antigen Receptor Specificity Vagina |
| Grant Support | |
ID/Acronym/Agency:
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AI-067854/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antigens; 0/Cytokines |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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