Cell-Mediated Immune Responses to Human Papillomavirus 16 E6 and E7 Antigens as Measured by Interferon Gamma Enzyme-Linked Immunospot in Women With Cleared or Persistent Human Papillomavirus Infection

Abstract

Cell mediated immune responses have been thought to be important in the control of HPV infections. We examined cell-mediated immune responses to HPV 16 E6 and E7 in the peripheral blood using IFN-γ enzyme-linked ImmunoSpot (ELISpot) assay in women with HPV 16 infection who showed clearance and compared these women to women with HPV 16 persistence. Women participating in a longitudinal study of cervical HPV were recruited once cervical HPV 16 infection was detected by PCR. Four groups of women were examined; 1) persistent 2) intermittent 3) transient and 4) cleared. Ninety-six samples from 55 women were compared. Comparing IFN-γ ELISpot to HPV 16 clearance, of 10 women with recent persistence, none had response to either E6 or E7; 14/24 women with recent clearance had E6 and 8/24 had E7 response. Women with intermittent persistence behaved similar to clearance group than recent persistors: 50% were positive to E6 and 20% to E7. In summary, anti E6 responses appeared critical in the immediate control of HPV and in some women an immune tolerance eventually develops if HPV is not eliminated soon after infection.

Phase II trial of imiquimod and HPV therapeutic vaccination in patients with vulval intraepithelial neoplasia

“…HPV infection of the lower genital tract and its outcome are influenced by host immune response, virulence of the HPV, smoking and immunosuppression (Duong and Flowers, 2007;Sherman et al, 2008). Successful adaptive immune responses that lead to clearance of genital HPV infection are believed to be mediated by local T cell-mediated immunity (Farhat et al, 2009). The virus life cycle and several immune evasion mechanisms limit virus-specific immunity, facilitating persistent infection and the increased risk of carcinogenesis (Stern, 2005).…”

“…The virus life cycle and several immune evasion mechanisms limit virus-specific immunity, facilitating persistent infection and the increased risk of carcinogenesis (Stern, 2005). Indeed, it has been shown that patients with persistent HPV infection have depleted T-cell responses against the viral early gene products E2 and E6 measured systemically (de Jong et al, 2004;Farhat et al, 2009). In addition, T regulatory cells are negative regulators of otherwise useful anti-tumour T-cell immunity and locally increased levels have been implicated in the persistence of both cervical and vulval HPVassociated lesions (van der Burg et al, 2007;Winters et al, 2008).…”

GTL001, A Therapeutic Vaccine for Women Infected with Human Papillomavirus 16 or 18 and Normal Cervical Cytology: Results of a Phase I Clinical Trial

“…A T-cell-mediated immune response against HPV antigens is important in controlling progression to CIN by sustaining viral clearance (31). The systemic and local reactions induced by GTL001 were consistent with the pharmacologic effects of a vaccine inducing a T-cell response.…”

Development of a Novel Liquid Bead Array Human Papillomavirus Genotyping Assay (PGMY-LX) and Comparison with Linear Array for Continuity in Longitudinal Cohort Studies

“…Cervicovaginal lavage (CVL) samples were collected at 4-to 6-month intervals from women participating in an ongoing study of the natural history of HPV infection in adolescents described elsewhere (19). All participants provided informed consent according to the guidelines set forth by the committee for human research, University of California, San Francisco.…”