Skin test for HPV type 16 proteins in cervical intraepithelial neoplasia

Höpfl, Reinhard; Sandbichler, Markus; Sepp, Norbert; Heim, K.; Müller‐Holzner, Elisabeth; Wartusch, B.; Dapunt, O; Jochmus-Kudielka, I.; Meulen, Jan ter; Gissmann, Lutz; Fritsch, Peter

doi:10.1016/0140-6736(91)91014-l

Cited by 24 publications

(12 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…21-23 H€ opfl et al were the first to study HPV16-specific cellular immunity by skin test in humans 24,25 and showed that a skin reaction, appearing within 2-6 days after intradermal injection with HPV16 E7, was correlated with regression of HPV-induced CIN lesions.…”

Section: 12mentioning

confidence: 99%

“…24,25 The skin test preparations consisted of 8 pools of long clinical-grade synthetic peptides spanning the whole HPV16 E6 and E7 protein and the most immunogenic regions of HPV16 E2 protein.…”

Section: Dth Skin Testmentioning

confidence: 99%

“…The pools of peptides and a negative control (vehicle of solvent only) were injected separately at individual skin test sites of the upper arm. Skin test sites were inspected at least 3 times, at 72 hr and 7 days after injection of the peptides 24,25 and at 3 weeks following the first report of a very late skin reaction in one of the first healthy subjects. Reactions were considered positive when papules greater than 2 mm in diameter arose no less than 2 days after injection.…”

Section: Subjectsmentioning

confidence: 99%

“…[14][15][16] Delayed-type hypersensitivity reactions have been used to demonstrate an encounter with pathogens (e.g., Mantoux Test), vaccineinduced immune responses, [17][18][19][20] and in particular to show HPVspecific immune responses in various animal models. [21][22][23] H€ opfl et al were the first to study HPV16-specific cellular immunity by skin test in humans 24,25 and showed that a skin reaction, appearing within 2-6 days after intradermal injection with HPV16 E7, was correlated with regression of HPV-induced CIN lesions.…”

mentioning

confidence: 99%

See 3 more Smart Citations

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

Hende

Poelgeest

Hulst

et al. 2008

Intl Journal of Cancer

View full text Add to dashboard Cite

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 5 11) and healthy individuals (n 5 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 HPV161 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 CD41 Th1/Th2 and CD81 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.Key words: HPV16/delayed type hypersensitivity; cellular immunity; ELISPOT; skin testThe main cause of cervical carcinoma and cervical intraepithelial neoplasia (CIN) is a persistent infection with one of the highrisk, oncogenic human papilloma viruses.1,2 Anogenital infection with a high-risk HPV type is very common.3-5 The rate of incidence of infection is estimated to be 80-85% worldwide.6 Fortunately, the majority of infected subjects will clear the virus infection within a year 7,8 , and only a small proportion of women will become persistently infected and are at risk to develop HPVrelated malignancies.9,10 Cell-mediated immune responses play an important role in controlling HPV infections. 11,12Delayed Type IV hypersensitivity (DTH) reactions are used as a general measure of cell-mediated immunity in vivo.13 A local inflammatory reaction (induration and erythema), orchestrated by activated cytokine releasing CD41 memory T cells, usually appears within 24-72 hr after intradermal injection of antigen. [14][15][16] Delayed-type hypersensitivity reactions have been used to demonstrate an encounter with pathogens (e.g., Mantoux Test), vaccineinduced immune responses, [17][18][19][20] and in particular to show HPVspecific immune responses in various animal models.21-23 H€ opfl et al. were the first to study HPV16-specific cellular immunity by skin test in humans 24,25 and showed that a skin reaction, appearing within 2-6 days after intradermal injection with HPV16 E7, was correlated with regression of HPV-induced CIN lesions.We have previously studied the HPV16-specific T-cell responses in great detail in vitro, and the results of these studies suggested that the HPV16 E2, E6 and E7 specific Type 1 and Type 2 T-cell response ...

show abstract

Section: 12mentioning

confidence: 99%

Section: Dth Skin Testmentioning

confidence: 99%

Section: Subjectsmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

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

Hende

Poelgeest

Hulst

et al. 2008

Intl Journal of Cancer

View full text Add to dashboard Cite

show abstract

“…For some time it has been known that the ability to mount a D T H reaction to specific viral or non-specific antigens is a factor in wart immunity (Thivolet et al, 1977). For example, positive skin tests have been reported in patients with regressing warts or with a history of past warts challenged with purified papillomavirus capsid antigen (Viac et al, 1977), in CIN patients on challenge with HPV-16 L 1 peptides expressed as recombinant bacterial fusion proteins (Hopfl et al, 1991), whereas contact dermatitis induced by dinitrochlorobenzene at the site of recalcitrant verrucae provokes their rejection (Greenberg et al, 1973). To date, the bulk of ceil-mediated immunity studies on HPV-16 have focused on responses to the E7 protein with a few notable exceptions.…”

mentioning

confidence: 99%

Delayed-type hypersensitivity response to human papillomavirus type 16 E6 protein in a mouse model

Chambers

Stacey

Arrand

et al. 1994

Journal of General Virology

View full text Add to dashboard Cite

A mouse model incorporating the epitheliotropic nature of human papillomavirus (HPV) infections has been used to study an immune response to HPV type 16 (HPV-16) E6 protein in vivo. Using a transplantation technique, a novel immortal keratinocyte cell line expressing the E6 protein has been grafted onto syngeneic mice to re-form a differentiated epithelium overlying a granulation tissue bed. By this approach the presentation of viral antigens to the immune system can be modelled in a way analogous to the natural infection. Here we report a delayed-type hypersensitivity (DTH) reaction in grafted mice challenged intradermally with a recombinant vaccinia virus expressing the HPV-16 E6 protein. The specificity of the response was confirmed by the absence ofa DTH reaction to challenge with virus expressing either HPV-16 E7 or LI protein.More than 65 different types of human papillomavirus (HPV) have been described, classified on the basis of nucleotide homology. At least 20 genotypes are associated with lesions of the genital tract. Benign genital warts (condylomata acuminata of low malignant potential) are most frequently associated with types 6 and 11, whereas types 16 and 18 are found predominantly in anogenital dysplasias and carcinomas.Our understanding of the immunobiology of papillomaviruses, although limited, is central to any strategy for prophylactic or therapeutic intervention. The evidence from immunosuppressed patients (Alloub et al.,

show abstract

Vaccination Against Cutaneous and Mucosal Papillomavirus in Cattle

Campo

Jarrett

2007

Ciba Foundation Symposium 187 ‐ Vaccines Against Virally Induced Cancers

View full text Add to dashboard Cite

Skin test for HPV type 16 proteins in cervical intraepithelial neoplasia

Cited by 24 publications

References 4 publications

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

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

Delayed-type hypersensitivity response to human papillomavirus type 16 E6 protein in a mouse model

Vaccination Against Cutaneous and Mucosal Papillomavirus in Cattle

Contact Info

Product

Resources

About