|Intravaginal immunization with HPV vectors induces tissue-resident CD8+ T cell responses.|
|PMID: 23143305 Owner: NLM Status: MEDLINE|
|The induction of persistent intraepithelial CD8+ T cell responses may be key to the development of vaccines against mucosally transmitted pathogens, particularly for sexually transmitted diseases. Here we investigated CD8+ T cell responses in the female mouse cervicovaginal mucosa after intravaginal immunization with human papillomavirus vectors (HPV pseudoviruses) that transiently expressed a model antigen, respiratory syncytial virus (RSV) M/M2, in cervicovaginal keratinocytes. An HPV intravaginal prime/boost with different HPV serotypes induced 10-fold more cervicovaginal antigen-specific CD8+ T cells than priming alone. Antigen-specific T cell numbers decreased only 2-fold after 6 months. Most genital antigen-specific CD8+ T cells were intra- or subepithelial, expressed αE-integrin CD103, produced IFN-γ and TNF-α, and displayed in vivo cytotoxicity. Using a sphingosine-1-phosphate analog (FTY720), we found that the primed CD8+ T cells proliferated in the cervicovaginal mucosa upon HPV intravaginal boost. Intravaginal HPV prime/boost reduced cervicovaginal viral titers 1,000-fold after intravaginal challenge with vaccinia virus expressing the CD8 epitope M2. In contrast, intramuscular prime/boost with an adenovirus type 5 vector induced a higher level of systemic CD8+ T cells but failed to induce intraepithelial CD103+CD8+ T cells or protect against recombinant vaccinia vaginal challenge. Thus, HPV vectors are attractive gene-delivery platforms for inducing durable intraepithelial cervicovaginal CD8+ T cell responses by promoting local proliferation and retention of primed antigen-specific CD8+ T cells.|
|Nicolas Çuburu; Barney S Graham; Christopher B Buck; Rhonda C Kines; Yuk-Ying S Pang; Patricia M Day; Douglas R Lowy; John T Schiller|
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|Type: Journal Article; Research Support, N.I.H., Intramural Date: 2012-11-12|
|Title: The Journal of clinical investigation Volume: 122 ISSN: 1558-8238 ISO Abbreviation: J. Clin. Invest. Publication Date: 2012 Dec|
|Created Date: 2012-12-03 Completed Date: 2013-02-04 Revised Date: 2013-07-11|
Medline Journal Info:
|Nlm Unique ID: 7802877 Medline TA: J Clin Invest Country: United States|
|Languages: eng Pagination: 4606-20 Citation Subset: AIM; IM|
|Laboratory of Cellular Oncology, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA.|
|APA/MLA Format Download EndNote Download BibTex|
Antigens, Viral / biosynthesis
CD8-Positive T-Lymphocytes / immunology*, metabolism, physiology
Human papillomavirus 16 / genetics*, immunology
Interferon-gamma / metabolism
Luciferases, Firefly / biosynthesis, genetics
Lymph Nodes / immunology
Mice, Inbred BALB C
Mucous Membrane / immunology, virology
Papillomavirus Vaccines / administration & dosage*, genetics
Respiratory Syncytial Virus Infections / prevention & control
Respiratory Syncytial Viruses / immunology
Spleen / immunology
Tumor Necrosis Factor-alpha / metabolism
Vaccines, Synthetic / administration & dosage, genetics
Vaccinia virus / genetics, immunology
Vagina / immunology, virology
|0/Antigens, Viral; 0/Papillomavirus Vaccines; 0/Tumor Necrosis Factor-alpha; 0/Vaccines, Synthetic; 82115-62-6/Interferon-gamma; EC 188.8.131.52/Luciferases, Firefly|
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