The Clinical Core unit is designed to procure serum, peripheral blood leukocytes (PBLs), and wart biopsies from patients with anogenital warts, both at baseline and as the wart is regressing. These samples as well as similar ones already from healthy volunteers immunized with an HPV-11 virus-like particle vaccine will be used to support the studies described in the three projects of the application. 18 to 65 year-old patients with anogenital warts will be enrolled in the wart procurement protocol if they have at least 6 warts at entry (two larger than 98 MM2). Patients will be excluded if they are unable to maintain the clinic visit schedule, unable to be reached by telephone, have had prior autogenous vaccination, topical or systemic antiviral or anti-wart therapy within two weeks of enrollment, treatment with medications, altering the immune system within 4 weeks prior to study entry, immunodeficiency or autoimmune disease, diabetes mellitus, positive HIV serology, pregnancy, breastfeeding, and presence of cervical squamous intra-epithelial lesion or cancer by Pap smear. Patients will undergo biopsies of their warts and normal buttock skin for the preparation of an autogenous vaccine from the wart(s) and of a placebo from the normal skin, as well as for the recovery of wart infiltrating lymphocytes. In addition, serum and Pbls will be obtained. The patient will be then randomized to receive his/her autogenous vaccine or placebo in a 2:1 ratio. We plan to recruit 75 evaluable patients. The vaccine will be administered subcutaneously and weekly for six weeks. During that period, as well as seven weeks afterwards subcutaneously and weekly for six weeks. During that period, as well as seven weeks afterwards, patients will be monitored for wart response. Should they develop regressing warts, one of the largest lesions will be promptly biopsied, and serum and PBLs obtained. If there is no wart regression, these procedures will be done 12 weeks after the first vaccination. Patients who still have warts then will be offered cryotherapy. Those patients free of disease will be followed every week weeks for an additional 12 weeks. Follow-up will help establish the correlates between the immunologic events and the clinical outcomes.
| Divekar, Anagha A; Zaiss, Dietmar M W; Lee, F Eun-Hyung et al. (2006) Protein vaccines induce uncommitted IL-2-secreting human and mouse CD4 T cells, whereas infections induce more IFN-gamma-secreting cells. J Immunol 176:1465-73 |
| Guess, Jennifer C; McCance, Dennis J (2005) Decreased migration of Langerhans precursor-like cells in response to human keratinocytes expressing human papillomavirus type 16 E6/E7 is related to reduced macrophage inflammatory protein-3alpha production. J Virol 79:14852-62 |
