title: Vaccination trial with HPV16 L1E7 chimeric virus-like particles in women suffering from high grade cervical intraepithelial neoplasia (CIN 2/3).
abstract: Persistent infection with human papillomaviruses (HPV) is a prerequisite for the development of cervical cancer. Vaccination with virus-like particles (VLP) has demonstrated efficacy in prophylaxis but lacks therapeutic potential. HPV16 L1E7 chimeric virus-like particles (CVLP) consist of a carboxy-terminally truncated HPV16L1 protein fused to the amino-terminal part of the HPV16 E7 protein and self-assemble by recombinant expression of the fusion protein. The CVLP are able to induce L1- and E7-specific cytotoxic T lymphocytes. We have performed a first clinical trial to gain information about the safety and to generate preliminary data on the therapeutic potential of the CVLP in humans. A randomized, double blind, placebo-controlled clinical trial has been conducted in 39 HPV16 mono-infected high grade cervical intraepithelial neoplasia (CIN) patients (CIN 2/3). Two doses (75 mug or 250 mug) of CVLP were applied. The duration of the study was 24 weeks with 2 optional visits after another 12 and 24 weeks. The vaccine showed a very good safety profile with only minor adverse events attributable to the immunization. Antibodies with high titers against HPV16 L1 and low titers against HPV16 E7 as well as cellular immune responses against both proteins were induced. Responses were equivalent for both vaccine concentrations. A trend for histological improvement to CIN 1 or normal was seen in 39% of the patients receiving the vaccine and only 25% of the placebo recipients. Fifty-six percent of the responders were also HPV16 DNA-negative by the end of the study. Therefore, we demonstrated evidence for safety and a nonsignificant trend for the clinical efficacy of the HPV16 L1E7 CVLP vaccine.
authors.affiliation: Klinik für Frauenheilkunde und Geburtshilfe, Friedrich-Schiller-Universität, Bachstrasse 18, 07740 Jena, Germany.
authors.forename: Andreas M
authors.initials: AM
authors.lastname: Kaufmann
authors.forename: John D
authors.initials: JD
authors.lastname: Nieland
authors.forename: Ingrid
authors.initials: I
authors.lastname: Jochmus
authors.forename: Siegfried
authors.initials: S
authors.lastname: Baur
authors.forename: Klaus
authors.initials: K
authors.lastname: Friese
authors.forename: Joseph
authors.initials: J
authors.lastname: Gabelsberger
authors.forename: Friederike
authors.initials: F
authors.lastname: Gieseking
authors.forename: Lutz
authors.initials: L
authors.lastname: Gissmann
authors.forename: Birgit
authors.initials: B
authors.lastname: Glasschröder
authors.forename: Thomas
authors.initials: T
authors.lastname: Grubert
authors.forename: Peter
authors.initials: P
authors.lastname: Hillemanns
authors.forename: Reinhard
authors.initials: R
authors.lastname: Höpfl
authors.forename: Hans
authors.initials: H
authors.lastname: Ikenberg
authors.forename: Jörg
authors.initials: J
authors.lastname: Schwarz
authors.forename: Matthias
authors.initials: M
authors.lastname: Karrasch
authors.forename: Anette
authors.initials: A
authors.lastname: Knoll
authors.forename: Volkmar
authors.initials: V
authors.lastname: Küppers
authors.forename: Martin
authors.initials: M
authors.lastname: Lechmann
authors.forename: Ralph J
authors.initials: RJ
authors.lastname: Lelle
authors.forename: Harald
authors.initials: H
authors.lastname: Meissner
authors.forename: Rainer T
authors.initials: RT
authors.lastname: Müller
authors.forename: Michael
authors.initials: M
authors.lastname: Pawlita
authors.forename: Karl Ulrich
authors.initials: KU
authors.lastname: Petry
authors.forename: Henryk
authors.initials: H
authors.lastname: Pilch
authors.forename: Elke
authors.initials: E
authors.lastname: Walek
authors.forename: Achim
authors.initials: A
authors.lastname: Schneider
mesh_terms: D000328:Adult; D000368:Aged; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004279:DNA, Viral / Q000187:drug effects / Q000302:isolation & purification; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D052162:Human papillomavirus 16 / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D009856:Oncogene Proteins, Viral / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D030361:Papillomavirus Infections / Q000150:complications / Q000188:drug therapy / Q000276:immunology; D053918:Papillomavirus Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D014412:Tumor Virus Infections / Q000150:complications / Q000188:drug therapy / Q000276:immunology; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000821:virology*; D002578:Uterine Cervical Dysplasia / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000821:virology*
chemical_list: D019496:Cancer Vaccines; D004279:DNA, Viral; C424202:HPV16 L1E7 chimeric virus-like particle; D015514:Oncogene Proteins, Fusion; D009856:Oncogene Proteins, Viral; D053918:Papillomavirus Vaccines