Epithelial boost enhances antigen expression by vaccinia virus for the generation of potent CD8+ T cell-mediated antitumor immunity following DNA priming vaccination

Jin Qiu, Shiwen Peng, Ying Ma, Andrew Yang, Emily Farmer, Max A. Cheng, Richard S Roden, Tzyy Choou Wu, Yung Nien Chang, Chien-Fu Hung

Research output: Contribution to journalArticle

Abstract

While both pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine and TA-HPV recombinant vaccinia viral vector-based vaccines have elicited HPV-specific CD8+ T cell responses in HPV16/E7-expressing tumor models, and been used as prime-boost regimen to enhance HPV-specific immune responses in humans (NCT00788164), the optimal route of administration for TA-HPV remains unclear. In a preclinical model, we examined the immunogenicity of priming with intramuscular pNGVL4a-Sig/E7(detox)/HSP70 followed by TA-HPV boost through different administration routes. We observed that priming twice with a pNGVL4a-Sig/E7(detox)/HSP70 followed by a single TA-HPV immunization boost through skin scarification generated the strongest antigen-specific CD8+ T cell response in C57BL/6 mice. These data translate to tumor control and prolonged survival of treated mice. Our results provide rationale for future clinical testing of intramuscular pNGVL4a-Sig/E7(detox)/HSP70 DNA vaccine prime, TA-HPV vaccine skin scarification boost immunization regimen for the control of HPV-associated diseases.

Original languageEnglish (US)
Pages (from-to)205-215
Number of pages11
JournalVirology
Volume525
DOIs
StatePublished - Dec 1 2018

Fingerprint

DNA Vaccines
Vaccinia virus
Cellular Immunity
Immunization
Vaccination
CD8 Antigens
T-Lymphocytes
Antigens
Vaccinia
Skin
DNA
Inbred C57BL Mouse
Neoplasms
Vaccines
Survival
TA human papillomavirus vaccine

Keywords

  • Human papillomavirus
  • pNGVL4a-Sig/E7(detox)/HSP70
  • Pre-clinical model
  • TA-HPV
  • Therapeutic HPV vaccine

ASJC Scopus subject areas

  • Virology

Cite this

Epithelial boost enhances antigen expression by vaccinia virus for the generation of potent CD8+ T cell-mediated antitumor immunity following DNA priming vaccination. / Qiu, Jin; Peng, Shiwen; Ma, Ying; Yang, Andrew; Farmer, Emily; Cheng, Max A.; Roden, Richard S; Wu, Tzyy Choou; Chang, Yung Nien; Hung, Chien-Fu.

In: Virology, Vol. 525, 01.12.2018, p. 205-215.

Research output: Contribution to journalArticle

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