Induction of immune memory following administration of a prophylactic quadrivalent human papillomavirus (HPV) types 6/11/16/18 L1 virus-like particle (VLP) vaccine

Vaccine. 2007 Jun 21;25(26):4931-9. doi: 10.1016/j.vaccine.2007.03.049. Epub 2007 Apr 20.


Background: The duration of protection afforded by vaccines represents a critical test of their utility as public health interventions. Some vaccines induce long-term immunity, while others require booster doses. Vaccines that induce long-term protection are usually characterized by the generation of immune memory. Recent trials of a quadrivalent (types 6, 11, 16, 18) human papillomavirus (HPV) vaccine have demonstrated high efficacy through 5 years of follow-up. We evaluated the extent to which the vaccine is able to generate HPV type-specific immune memory.

Methods: A total of 552, 16-23-year-old women were enrolled in a double-blind, placebo-controlled study. At enrollment, subjects were randomized in a 1:1 ratio to receive three-dose regimens of quadrivalent HPV vaccine or placebo with 3 years' follow-up. A subset of 241 subjects (n=114 in the quadrivalent HPV vaccine group and n=127 in the placebo group) underwent 2 further years of follow-up. All extension subjects received quadrivalent HPV vaccine at month 60 to examine the extent of immune memory in response to the primary vaccination series.

Results: Serum anti-HPV levels declined post-vaccination, but reached a plateau at month 24 that remained stable through month 60. Administration of a challenge dose of vaccine induced a classic anamnestic response, with anti-HPV levels 1 week post-challenge reaching levels observed 1 month following the completion of the three-dose primary series. At 1 month post-challenge, anti-HPV responses were higher than those observed 1-month post-dose 3.

Discussion: A three-dose regimen of quadrivalent HPV vaccine induces high efficacy and stable anti-HPV levels for at least 5 years. Vaccination also induces robust immune memory. These findings suggest that the efficacy of this vaccine will be long lasting.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Viral / blood
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Follow-Up Studies
  • Human papillomavirus 11 / immunology
  • Human papillomavirus 16 / immunology
  • Human papillomavirus 18 / immunology
  • Humans
  • Immunization Schedule
  • Immunologic Memory / immunology*
  • Papillomavirus Infections / immunology*
  • Papillomavirus Infections / prevention & control*
  • Papillomavirus Vaccines / immunology*


  • Antibodies, Viral
  • Papillomavirus Vaccines