Skin reactions to human papillomavirus (HPV) 16 specific antigens intradermally injected in healthy subjects and patients with cervical neoplasia.
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.
van den Hende
Muriel
M
Department of Gynecology, Leiden University Medical Center, Leiden, The Netherlands.
van Poelgeest
Mariëtte I E
MI
van der Hulst
Jeanette M
JM
de Jong
Joan
J
Drijfhout
Jan W
JW
Fleuren
Gert Jan
GJ
Valentijn
A Rob P M
AR
Wafelman
Amon R
AR
Slappendel
Gijs M
GM
Melief
Cornelis J M
CJ
Offringa
Rienk
R
van der Burg
Sjoerd H
SH
Kenter
Gemma G
GG
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
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