Immunology

Characterization of human papillomavirus type 11-specific immune responses in a preclinical model†

  1. Shiwen Peng MD, PhD1,2,3,
  2. Simon R. Best MD1,
  3. Chien-Fu Hung MD, PhD2,3,
  4. Myriam Loyo MD1,
  5. Sofia Lyford-Pike MD1,
  6. Paul W. Flint MD7,
  7. David E. Tunkel MD1,
  8. John R. Saunders MD1,6,
  9. T. C. Wu MD, PhD2,3,4,5,
  10. Sara I. Pai MD, PhD1,5,*

Article first published online: 18 DEC 2009

DOI: 10.1002/lary.20745

Issue

The Laryngoscope

The Laryngoscope

Volume 120, Issue 3, pages 504–510, March 2010

Additional Information

How to Cite

Peng, S., Best, S. R., Hung, C.-F., Loyo, M., Lyford-Pike, S., Flint, P. W., Tunkel, D. E., Saunders, J. R., Wu, T. C. and Pai, S. I. (2010), Characterization of human papillomavirus type 11-specific immune responses in a preclinical model. The Laryngoscope, 120: 504–510. doi: 10.1002/lary.20745

Author Information

  1. 1

    Department of Otolaryngology–Head and Neck SurgeryBaltimore, Maryland, U.S.A.

  2. 2

    Department of Pathology, Baltimore, Maryland, U.S.A.

  3. 3

    Department of Obstetrics and Gynecology, Baltimore, Maryland, U.S.A.

  4. 4

    Department of Molecular Microbiology and Immunology, Baltimore, Maryland, U.S.A.

  5. 5

    Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, Maryland, U.S.A.

  6. 6

    Johns Hopkins Medical Institutions, the Milton J. Dance, Jr. Head and Neck Center at Greater Baltimore Medical Center, Baltimore, Maryland

  7. 7

    Department of Otolaryngology, Oregon Health and Science University, Portland, Oregon, U.S.A.

*Department of Otolaryngology–Head and Neck Surgery, Johns Hopkins Medical Institutions, 601 North Caroline Street, Baltimore, MD 21287

  1. †

    The authors have no conflicting financial interests.

Publication History

  1. Issue published online: 16 FEB 2010
  2. Article first published online: 18 DEC 2009
  3. Manuscript Accepted: 9 SEP 2009

Funded by

  • The Milton J. Dance, Jr. Head and Neck Center at the Greater Baltimore Medical Center
  • William F. Reinhoff Jr. MD Scholars Program at the Johns Hopkins University

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Keywords:

  • HPV-11;
  • DNA vaccine;
  • epitope

Abstract

Objectives/Hypothesis:

Human papillomavirus (HPV) types 6 and 11 are associated with recurrent respiratory papillomatosis (RRP). Although a prophylactic vaccine has been developed that protects against HPV infection, a therapeutic vaccine is still needed for those patients infected with and/or suffering from persistent disease. Therefore, we developed a novel, therapeutic DNA vaccine targeting HPV-11 and characterized the in vivo immunologic responses generated against HPV-11 E6 and E7 after DNA vaccination in a preclinical model.

Methods:

We generated a DNA vaccine that encodes the HPV-11 E6 and E7 genes in a pcDNA3 backbone plasmid. We then vaccinated C57BL/6 mice with the pcDNA3-HPV11-E6E7 DNA plasmid. Splenocytes were harvested from these vaccinated animals and were incubated with overlapping peptides spanning either the HPV-11 E6 or E7 protein. The frequency of interferon-γ–releasing CD8+ T cell responses was then analyzed by flow cytometry.

Results:

Vaccinated mice with the HPV11-E6E7 DNA generated strong CD8+ T cell responses against the E6aa44-51 peptide. We determined that the epitope is presented by the MHC class I H2-Kb molecule. No significant E7 peptide-specific T cell responses were observed.

Conclusions:

We developed a novel DNA vaccine that targets the E6 gene of HPV-11. Characterization of the immunologic responses elicited by this DNA vaccine reveals that the E6aa44-51 peptide contains the most immunogenic region for the HPV-11 viral type. Knowledge of this specific T cell epitope and generation of a RRP preclinical model will allow for the development and evaluation of novel vaccine strategies targeting the RRP patient population. Laryngoscope, 2010

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