Skin reactions to human papillomavirus (HPV) 16 specific antigens intradermally injected in healthy subjects and patients with cervical neoplasia

• Published in: International journal of cancer Vol. 123; no. 1; pp. 146 - 152
• Main Authors: van den Hende, Muriel, van Poelgeest, Mariëtte I.E., van der Hulst, Jeanette M., de Jong, Joan, Drijfhout, Jan W., Fleuren, Gert Jan, Valentijn, A. Rob P.M., Wafelman, Amon R., Slappendel, Gijs M., Melief, Cornelis J.M., Offringa, Rienk, van der Burg, Sjoerd H., Kenter, Gemma G.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.07.2008; Wiley-Liss
• Subjects: Adult; Aged; Antigens, Viral - administration & dosage; Antigens, Viral - immunology; Biological and medical sciences; cellular immunity; Cross-Sectional Studies; Cytokines - immunology; DNA-Binding Proteins - administration & dosage; DNA-Binding Proteins - immunology; ELISPOT; Feasibility Studies; Female; Female genital diseases; Gynecology. Andrology. Obstetrics; HPV16/delayed type hypersensitivity; Human papillomavirus 16; Human papillomavirus 16 - immunology; Humans; Hysterectomy; Injections, Intradermal; Medical sciences; Middle Aged; Oncogene Proteins, Viral - administration & dosage; Oncogene Proteins, Viral - immunology; Papillomavirus E7 Proteins; Repressor Proteins - administration & dosage; Repressor Proteins - immunology; Skin - immunology; Skin - virology; skin test; Skin Tests - methods; Tumors; Uterine Cervical Neoplasms - immunology; Uterine Cervical Neoplasms - surgery; Uterine Cervical Neoplasms - virology; Human; Premalignant lesion; Immune response; Healthy subject; HPV16/delayed type hypersensitivity; Exploration; Delayed hypersensitivity; Cellular immunity; Intradermal administration; Papovaviridae; Uterine cervix; Enzyme immunoassay; ELISPOT; Female genital diseases; Papillomavirus; Virus; Antigen; Human papillomavirus 16; Human papillomavirus; Cancerology; Cervical intraepithelial neoplasia; Uterine cervix diseases; Skin test
• ISSN: 0020-7136; 1097-0215; 1097-0215
• DOI: 10.1002/ijc.23502

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. © 2008 Wiley‐Liss, Inc.