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

Shiwen Peng, Simon R. Best, Chien Fu Hung, Myriam Loyo, Sofia Lyford-Pike, Paul Flint, David E. Tunkel, John R. Saunders, T. C. Wu, Sara I. Pai

Research output: Contribution to journalArticle

10 Citations (Scopus)

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 E6 aa44-51 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.

Original languageEnglish (US)
Pages (from-to)504-510
Number of pages7
JournalLaryngoscope
Volume120
Issue number3
DOIs
StatePublished - Mar 2010

Fingerprint

Human papillomavirus 11
DNA Vaccines
Vaccines
T-Lymphocytes
Peptides
DNA
Plasmids
Human papillomavirus 6
Peptide T
T-Lymphocyte Epitopes
Papillomavirus Infections
Inbred C57BL Mouse
Interferons
Genes
Epitopes
Flow Cytometry
Vaccination
Therapeutics
Population
Recurrent respiratory papillomatosis

Keywords

  • DNA vaccine
  • Epitope
  • HPV-11

ASJC Scopus subject areas

  • Otorhinolaryngology

Cite this

Characterization of human papillomavirus type 11-specific immune responses in a preclinical model. / Peng, Shiwen; Best, Simon R.; Hung, Chien Fu; Loyo, Myriam; Lyford-Pike, Sofia; Flint, Paul; Tunkel, David E.; Saunders, John R.; Wu, T. C.; Pai, Sara I.

In: Laryngoscope, Vol. 120, No. 3, 03.2010, p. 504-510.

Research output: Contribution to journalArticle

Peng, S, Best, SR, Hung, CF, Loyo, M, Lyford-Pike, S, Flint, P, Tunkel, DE, Saunders, JR, Wu, TC & Pai, SI 2010, 'Characterization of human papillomavirus type 11-specific immune responses in a preclinical model', Laryngoscope, vol. 120, no. 3, pp. 504-510. https://doi.org/10.1002/lary.20745
Peng, Shiwen ; Best, Simon R. ; Hung, Chien Fu ; Loyo, Myriam ; Lyford-Pike, Sofia ; Flint, Paul ; Tunkel, David E. ; Saunders, John R. ; Wu, T. C. ; Pai, Sara I. / Characterization of human papillomavirus type 11-specific immune responses in a preclinical model. In: Laryngoscope. 2010 ; Vol. 120, No. 3. pp. 504-510.
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AU - Best, Simon R.

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AU - Loyo, Myriam

AU - Lyford-Pike, Sofia

AU - Flint, Paul

AU - Tunkel, David E.

AU - Saunders, John R.

AU - Wu, T. C.

AU - Pai, Sara I.

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N2 - 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 E6 aa44-51 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.

AB - 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 E6 aa44-51 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.

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KW - Epitope

KW - HPV-11

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