Epitopes described in "Intravaginal immunization with HPV vectors induces tissue-resident CD8+ T cell responses."

Article Authors:Nicolas Çuburu; Barney S Graham; Christopher B Buck; Rhonda C Kines; Yuk-Ying S Pang; Patricia M Day; Douglas R Lowy; John T Schiller
Article Title:Intravaginal immunization with HPV vectors induces tissue-resident CD8+ T cell responses.
Reference Detail
Reference ID:1027354
Abstract: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 E-integrin CD103, produced IFN- and TNF-, 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.
Affiliations:Laboratory of Cellular Oncology, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA.
Reference Type:Literature
PubMed ID:23143305
Journal:J Clin Invest
Journal Volume:122
Article Pages:4606-20
Journal ISSN:0021-9738
Article Chemical List:Antigens, Viral;Papillomavirus Vaccines;Tumor Necrosis Factor-alpha;Vaccines, Synthetic;Interferon-gamma;Luciferases, Firefly
Article MeSH List:Administration, Intravaginal; Animals; Antigens, Viral(biosynthesis); CD8-Positive T-Lymphocytes(immunology; metabolism; physiology); Cell Proliferation; Cytotoxicity, Immunologic; Female; Genes, Reporter; Genetic Vectors; HEK293 Cells; Human papillomavirus 16(genetics; immunology); Humans; Immunization, Secondary; Immunologic Memory; Interferon-gamma(metabolism); Luciferases, Firefly(biosynthesis; genetics); Lymph Nodes(immunology); Mice; 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); Statistics, Nonparametric; Tumor Necrosis Factor-alpha(metabolism); Vaccination; Vaccines, Synthetic(administration & dosage; genetics); Vaccinia virus(genetics; immunology); Vagina(immunology; virology)
Curation Last Updated:2015-07-30 20:50:25