title: Skin reactions to human papillomavirus (HPV) 16 specific antigens intradermally injected in healthy subjects and patients with cervical neoplasia.
abstract: We have tested the safety and feasibility of a synthetic long peptide-based HPV16-specific skin test to detect cellular immune responses to HPV16 E2, E6 and E7 in vivo. Women with cervical neoplasia (n = 11) and healthy individuals (n = 19) were intradermally challenged with 8 different pools of HPV16 E2, E6 and E7 peptides. The skin test was safe as the injections were perceived as mildly painful and no adverse events were observed. The majority of skin reactions appeared significantly earlier in HPV16+ patients (<8 days) than in healthy subjects (8-25 days). The development of late skin reactions in healthy subjects was associated with the appearance of circulating HPV16-specific T cells and the infiltration of both HPV16-specific CD4+ Th1/Th2 and CD8+ T cells into the skin. These data show that the intradermal injection of pools of HPV16 synthetic long peptides is safe and results in the migration of HPV16-specific T cells into the skin as well as in an increase in the number of circulating HPV16-specific T cells. The use of this test to measure HPV16-specific immunity is currently tested in a low resource setting for the measurement of spontaneously induced T-cell responses as well as in our HPV16 vaccination trials for the detection of vaccine-induced immunity.
authors.affiliation: Department of Gynecology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Muriel
authors.initials: M
authors.lastname: van den Hende
authors.forename: Mariëtte I E
authors.initials: MI
authors.lastname: van Poelgeest
authors.forename: Jeanette M
authors.initials: JM
authors.lastname: van der Hulst
authors.forename: Joan
authors.initials: J
authors.lastname: de Jong
authors.forename: Jan W
authors.initials: JW
authors.lastname: Drijfhout
authors.forename: Gert Jan
authors.initials: GJ
authors.lastname: Fleuren
authors.forename: A Rob P M
authors.initials: AR
authors.lastname: Valentijn
authors.forename: Amon R
authors.initials: AR
authors.lastname: Wafelman
authors.forename: Gijs M
authors.initials: GM
authors.lastname: Slappendel
authors.forename: Cornelis J M
authors.initials: CJ
authors.lastname: Melief
authors.forename: Rienk
authors.initials: R
authors.lastname: Offringa
authors.forename: Sjoerd H
authors.initials: SH
authors.lastname: van der Burg
authors.forename: Gemma G
authors.initials: GG
authors.lastname: Kenter
mesh_terms: D000328:Adult; D000368:Aged; D000956:Antigens, Viral / Q000008:administration & dosage* / Q000276:immunology*; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000276:immunology; D004268:DNA-Binding Proteins / Q000008:administration & dosage / Q000276:immunology; D005240:Feasibility Studies; D005260:Female; D052162:Human papillomavirus 16 / Q000276:immunology*; D006801:Humans; D007044:Hysterectomy; D007271:Injections, Intradermal; D008875:Middle Aged; D009856:Oncogene Proteins, Viral / Q000008:administration & dosage / Q000276:immunology; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins / Q000008:administration & dosage / Q000276:immunology; D012867:Skin / Q000276:immunology* / Q000821:virology*; D012882:Skin Tests / Q000379:methods*; D002583:Uterine Cervical Neoplasms / Q000276:immunology* / Q000601:surgery / Q000821:virology
chemical_list: D000956:Antigens, Viral; D016207:Cytokines; D004268:DNA-Binding Proteins; C054855:E2 protein, Human papillomavirus type 16; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16