4 years ago

Immunologic responses to a novel DNA vaccine targeting human papillomavirus-11 E6E7

Chien-Fu Hung, Julie Ahn, Tzyy-Choou Wu, Richard B. S. Roden, Shiwen Peng, Simon R. Best
Objectives/Hypothesis Recurrent respiratory papillomatosis (RRP) is a benign disease caused by human papillomavirus (HPV) types 6 and 11. Although a prophylactic vaccine against RRP is available, a therapeutic vaccine is needed to treat those already infected. The objective of our study was to design and test a DNA vaccine targeting HPV11 proteins. Study Design Preclinical scientific investigation. Methods A DNA vaccine encoding the HPV11 E6 and E7 genes linked to calreticulin (CRT) was generated. Immunologic response to the HPV11 CRT/E6E7 vaccine was measured by vaccinating C57BL/6 mice via electroporation and measuring CD8 + T cell responses from harvested splenocytes. A tumor cell line containing HPV11-E6E7 was created, and the ability of novel DNA vaccine to control tumor growth was measured in vivo. Results Our vaccine generated a significant and specific CD8 + T-cell response against the HPV11-E6aa41-70 peptide. The CD8 + T-cell responses did not recognize E7 epitopes, indicating E6 immunodominance. CD8 + responses were augmented in the CRT-linked vaccine compared to a control non-CRT vaccine. The HPV11 CRT/E6E7 vaccine was used to treat mice inoculated with a HPV11 E6E7 expressing tumor cell line after temporary CD3 depletion to facilitate tumor growth. Vaccinated mice had a significantly lower tumor growth rate (P = .029) and smaller tumor volumes compared to control mice, indicating an augmented immunologic response in vaccinated mice. Conclusions A DNA vaccine targeting HPV11 E6E7 generates a specific HPV11 CD-8 + T-cell response capable of reducing the growth of HPV11-expressing tumors. DNA vaccines are a promising immunologic strategy for treating RRP. Level of Evidence NA. Laryngoscope, 127:2713–2720, 2017

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/lary.26737

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