Cancer Immunology, Immunotherapy

, Volume 63, Issue 2, pp 147–160 | Cite as

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

  • Peggy J. de Vos van Steenwijk
  • Mariette I. E. van Poelgeest
  • Tamara H. Ramwadhdoebe
  • Margriet J. G. Löwik
  • Dorien M. A. Berends-van der Meer
  • Caroline E. van der Minne
  • Nikki M. Loof
  • Linda F. M. Stynenbosch
  • Lorraine M. Fathers
  • A. Rob P. M. Valentijn
  • Jaap Oostendorp
  • Elisabeth M. Osse
  • Gert Jan Fleuren
  • Linda Nooij
  • Marjolein J. Kagie
  • Bart W. J. Hellebrekers
  • Cornelis J. M. Melief
  • Marij J. P. Welters
  • Sjoerd H. van der Burg
  • Gemma G. Kenter
Original Article

Abstract

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.

Keywords

CIN HPV16 Immunotherapy Vaccination Memory response 

Supplementary material

262_2013_1499_MOESM1_ESM.pdf (177 kb)
Supplementary material 1 (PDF 177 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Peggy J. de Vos van Steenwijk
    • 1
  • Mariette I. E. van Poelgeest
    • 1
  • Tamara H. Ramwadhdoebe
    • 2
  • Margriet J. G. Löwik
    • 1
  • Dorien M. A. Berends-van der Meer
    • 1
  • Caroline E. van der Minne
    • 2
  • Nikki M. Loof
    • 2
  • Linda F. M. Stynenbosch
    • 2
  • Lorraine M. Fathers
    • 3
  • A. Rob P. M. Valentijn
    • 3
  • Jaap Oostendorp
    • 3
  • Elisabeth M. Osse
    • 4
  • Gert Jan Fleuren
    • 4
  • Linda Nooij
    • 6
  • Marjolein J. Kagie
    • 6
  • Bart W. J. Hellebrekers
    • 7
  • Cornelis J. M. Melief
    • 5
    • 8
  • Marij J. P. Welters
    • 2
  • Sjoerd H. van der Burg
    • 2
  • Gemma G. Kenter
    • 1
    • 9
  1. 1.Department of GynecologyLeiden University Medical CenterLeidenThe Netherlands
  2. 2.Department of Clinical OncologyLeiden University Medical CenterLeidenThe Netherlands
  3. 3.Department of Clinical Pharmacology and ToxicologyLeiden University Medical CenterLeidenThe Netherlands
  4. 4.Department of PathologyLeiden University Medical CenterLeidenThe Netherlands
  5. 5.Department of Immunohaematology and Blood TransfusionLeiden University Medical CenterLeidenThe Netherlands
  6. 6.Department of Obstetrics and GynecologyMedical Centrum HaaglandenThe HagueThe Netherlands
  7. 7.Department of Obstetrics and GynecologyHaga Teaching HospitalThe HagueThe Netherlands
  8. 8.ISA PharmaceuticalsLeidenThe Netherlands
  9. 9.Center of Gynecologic Oncology AmsterdamAmsterdamThe Netherlands

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