Development of a DNA vaccine targeting Merkel cell polyomavirus

Qi Zeng, Bianca P. Gomez, Raphael P Viscidi, Shiwen Peng, Liangmei He, Barbara Ma, Tzyy Choou Wu, Chien-Fu Hung

Research output: Contribution to journalArticle

Abstract

Merkel cell carcinoma (MCC) is a rare but devastating skin disease that is increasing in incidence within the United States. The poor prognosis of MCC patients and limited understanding of MCC pathogenesis warrants innovative treatments to control MCC. Several lines of evidence have pointed to Merkel cell polyomavirus (MCPyV) as the etiological agent of MCC. In particular, the amino terminus of MCPyV large T antigen (LT) (aa1-258) is expressed in all MCPyV-positive tumors and plays an important role in MCC oncogenesis, rendering it an ideal therapeutic target for vaccination. In the current study, we developed a DNA vaccine encoding MCPyV LT aa1-258 (pcDNA3-LT). Within our pcDNA3-LT DNA vaccine, we identified that MCPyV LT aa136-160 likely contains an LT-specific CD4+ T helper epitope. We have also created an LT-expressing B16/LT tumor model using B16, a murine melanoma cell line, to characterize the potency of our DNA vaccine. Using this tumorigenic B16/LT tumor model, we found that pcDNA3-LT DNA vaccine generates antitumor effects mainly mediated by CD4+ T cells against B16/LT tumors in vaccinated C57BL/6 mice. Thus, immunotherapy using pcDNA3-LT DNA vaccine may represent a promising approach for the control of MCPyV-associated lesions. The B16/LT tumor model further serves as a useful model for testing various vaccine strategies against MCC.

Original languageEnglish (US)
Pages (from-to)1322-1329
Number of pages8
JournalVaccine
Volume30
Issue number7
DOIs
StatePublished - Feb 8 2012

Fingerprint

Merkel cell polyomavirus
Polyomavirus
DNA Vaccines
Viral Tumor Antigens
recombinant vaccines
Merkel Cell Carcinoma
antigens
carcinoma
Polyomavirus Transforming Antigens
cells
neoplasms
Neoplasms
Inbred C57BL Mouse
Skin Diseases
Immunotherapy
immunotherapy
Epitopes
etiological agents
mice
Melanoma

Keywords

  • DNA vaccine
  • Merkel cell carcinoma
  • Merkel cell polyomavirus

ASJC Scopus subject areas

  • Immunology and Microbiology(all)
  • Infectious Diseases
  • Public Health, Environmental and Occupational Health
  • veterinary(all)
  • Molecular Medicine

Cite this

Development of a DNA vaccine targeting Merkel cell polyomavirus. / Zeng, Qi; Gomez, Bianca P.; Viscidi, Raphael P; Peng, Shiwen; He, Liangmei; Ma, Barbara; Wu, Tzyy Choou; Hung, Chien-Fu.

In: Vaccine, Vol. 30, No. 7, 08.02.2012, p. 1322-1329.

Research output: Contribution to journalArticle

Zeng, Qi ; Gomez, Bianca P. ; Viscidi, Raphael P ; Peng, Shiwen ; He, Liangmei ; Ma, Barbara ; Wu, Tzyy Choou ; Hung, Chien-Fu. / Development of a DNA vaccine targeting Merkel cell polyomavirus. In: Vaccine. 2012 ; Vol. 30, No. 7. pp. 1322-1329.
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