The long-term immune response after HPV16 peptide vaccination in women with low-grade pre-malignant disorders of the uterine cervix: a placebo-controlled phase II study

Cancer Immunol Immunother. 2014 Feb;63(2):147-60. doi: 10.1007/s00262-013-1499-2. Epub 2013 Nov 15.


The capacity of a low-dose HPV16 synthetic long-peptide vaccine (HPV16-SLP) to induce an HPV16-specific T-cell response as well as to establish long-term immunologic memory in patients with low-grade abnormalities of the cervix was determined in a placebo-controlled, double-blinded phase II study. In addition, the effect of a booster vaccination after 1 year was evaluated. Patients received either the HPV16-SLP or a placebo at the start of the study. After 1 year, the vaccinated patients were again randomized to receive the HPV16-SLP or a placebo. Patients were followed for 2 years. HPV16-specific T-cell responses were determined in pre- and post-vaccination blood samples by ELISPOT, proliferation assay and cytokine assays. We show that the HPV16-specific T-cell responses detected after vaccination are clearly due to vaccination and that reactivity was maintained for at least 2 years. Interestingly, a booster vaccination after 1 year especially augmented the HPV16-specific Th2 response. Furthermore, pre-existing immunity to HPV16 was associated with a stronger response to vaccination and with more side effects, reflected by flu-like symptoms. We conclude that two low-dose injections of HPV16-SLP can induce a strong and stable HPV16-specific T-cell response that lasts for at least 1 year. If booster vaccination is required, then polarizing adjuvant should be added to maintain the Th1 focus of the vaccine-induced T-cell response.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Double-Blind Method
  • Female
  • Human papillomavirus 16 / immunology*
  • Humans
  • Immunologic Memory
  • Middle Aged
  • Neoplasm Grading
  • Papillomavirus Vaccines / immunology*
  • Precancerous Conditions / immunology*
  • T-Lymphocytes / immunology*
  • Uterine Cervical Neoplasms / immunology*
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / virology
  • Vaccination* / adverse effects
  • Vaccines, Subunit / immunology


  • Papillomavirus Vaccines
  • Vaccines, Subunit