title: Cellular immune responses to human papillomavirus (HPV)-16 L1 in healthy volunteers immunized with recombinant HPV-16 L1 virus-like particles.
abstract: The causal association between papillomavirus (HPV) infection and cervical cancer has been demonstrated; the development of a prophylactic vaccine to protect against HPV infection may therefore reduce the incidence of this cancer worldwide. Noninfectious HPV-like particles (VLPs), composed of the L1 major capsid protein, are current candidate vaccines for prevention of HPV infection and cervical neoplasia. Although neutralizing antibodies have a pivotal role in the prevention of initial infection, cellular immune responses to HPV antigens may have an important role in viral clearance. A phase II trial was conducted to further evaluate the immunogenicity of a recombinant HPV-16 L1 VLP vaccine administered intramuscularly, without adjuvant, at 0, 1, and 6 months. Cell-mediated immune responses (lymphoproliferation and cytokine production) to HPV-16 L1 VLPs were evaluated in peripheral blood mononuclear cells (PBMCs) from 43 individuals receiving the L1 VLP vaccine and from 10 individuals receiving placebo. Vaccination resulted, at months 2 and 7 (i.e., 1 month after the second immunization and 1 month after third immunization, respectively), in increases in T cell-proliferative response to HPV-16 L1 VLPs (P<.001). In addition, significant increases in cytokine (interferon-gamma, interleukin [IL]-5 and IL-10) responses to L1 VLPs were observed after vaccination (P<.001). The strongest cytokine responses at month 7 were observed in individuals with high antibody titers at month 2, suggesting that neutralizing antibodies generated by initial vaccination may augment T cell responses to subsequent booster vaccinations. No significant increases in lymphoproliferative or cytokine responses to L1 VLPs were observed in individuals receiving placebo. In summary, the HPV-16 L1 vaccine induces not only robust B cell responses but also L1-specific T cell responses detectable by proliferation of both CD4+ and CD8+ T cells and in vitro production of both Th1- and Th2-type cytokines. Future efficacy studies are needed to evaluate whether and/or how VLP vaccines confer protection against genital HPV infection and associated disease.
authors.affiliation: SAIC-Frederick, Inc./National Cancer Institute, Building 469, Room 120, Frederick, MD 21702, USA. lpinto@ncifcrf.gov
authors.forename: Ligia A
authors.initials: LA
authors.lastname: Pinto
authors.forename: Jessica
authors.initials: J
authors.lastname: Edwards
authors.forename: Philip E
authors.initials: PE
authors.lastname: Castle
authors.forename: Clayton D
authors.initials: CD
authors.lastname: Harro
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Lowy
authors.forename: John T
authors.initials: JT
authors.lastname: Schiller
authors.forename: Dora
authors.initials: D
authors.lastname: Wallace
authors.forename: William
authors.initials: W
authors.lastname: Kopp
authors.forename: Joseph W
authors.initials: JW
authors.lastname: Adelsberger
authors.forename: Michael W
authors.initials: MW
authors.lastname: Baseler
authors.forename: Jay A
authors.initials: JA
authors.lastname: Berzofsky
authors.forename: Allan
authors.initials: A
authors.lastname: Hildesheim
mesh_terms: D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D027383:Papillomaviridae / Q000276:immunology*; D013379:Substrate Specificity; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination; D014765:Viral Vaccines / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D016207:Cytokines; D014765:Viral Vaccines