Randomized controlled trial of an adjuvanted human papillomavirus (HPV) type 6 L2E7 vaccine: infection of external anogenital warts with multiple HPV types and failure of therapeutic vaccination

J Infect Dis. 2005 Dec 15;192(12):2099-107. doi: 10.1086/498164. Epub 2005 Nov 11.

Abstract

Background: Cellular immunity is involved in spontaneous clearance of anogenital warts caused, most typically, by human papillomavirus (HPV) type 6 or 11, supporting the concept of therapeutic vaccination. A therapeutic vaccine composed of HPV-6 L2E7 fusion protein and AS02A adjuvant was evaluated in conjunction with conventional therapies in subjects with anogenital warts.

Methods: A total of 457 subjects with anogenital warts were screened, of which 320 with HPV-6 and/or HPV-11 infection were enrolled into 2 double-blind, placebo-controlled substudies. Three doses of vaccine or placebo were administered along with either ablative therapy or podophyllotoxin.

Results: Although a positive trend toward clearance was seen in patients infected with only HPV-6, in neither substudy did the vaccine significantly increase the efficacy of conventional therapies, despite induction of adequate immune responses. Extensive HPV typing by polymerase chain reaction demonstrated that a majority of screened subjects (73.7%) were infected with HPV-6 and/or HPV-11 and that a large proportion (40.1%) were infected with multiple HPV types. HPV types that put subjects at high risk of development of cervical cancer were detected in 39.8% of subjects.

Conclusions: Infection with multiple HPV types, including high-risk types, is common in anogenital wart disease. Therapeutic vaccination failed to increase the efficacy of conventional therapies.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Adolescent
  • Adult
  • Capsid Proteins / genetics
  • Capsid Proteins / immunology*
  • Capsid Proteins / therapeutic use
  • Condylomata Acuminata / immunology
  • Condylomata Acuminata / therapy*
  • Condylomata Acuminata / virology*
  • DNA, Viral / genetics
  • DNA, Viral / isolation & purification
  • Double-Blind Method
  • Drug Combinations
  • Female
  • Genotype
  • Human papillomavirus 6 / genetics
  • Human papillomavirus 6 / immunology*
  • Humans
  • Lipid A / administration & dosage
  • Lipid A / analogs & derivatives
  • Lipid A / pharmacology
  • Male
  • Middle Aged
  • Oncogene Proteins, Viral / genetics
  • Oncogene Proteins, Viral / immunology*
  • Oncogene Proteins, Viral / therapeutic use
  • Papillomaviridae / classification*
  • Papillomaviridae / genetics
  • Papillomaviridae / isolation & purification
  • Papillomavirus Vaccines*
  • Placebos
  • Podophyllotoxin / administration & dosage
  • Polymerase Chain Reaction
  • Saponins / administration & dosage
  • Saponins / pharmacology
  • Vaccines, Synthetic / immunology
  • Vaccines, Synthetic / therapeutic use*
  • Viral Vaccines / therapeutic use*

Substances

  • ASO2A adjuvant
  • Adjuvants, Immunologic
  • Capsid Proteins
  • DNA, Viral
  • Drug Combinations
  • L2 oncogene viral capsid protein, Human papillomavirus type 6
  • Lipid A
  • Oncogene Proteins, Viral
  • Papillomavirus Vaccines
  • Placebos
  • Saponins
  • Vaccines, Synthetic
  • Viral Vaccines
  • oncogene protein E7, Human papillomavirus type 6
  • Podophyllotoxin