Characterization of human papillomavirus type 11-specific immune responses in a preclinical model.
OBJECTIVE
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-gamma-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 E6(aa44-51) peptide. We determined that the epitope is presented by the MHC class I H2-K(b) 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.
Peng
Shiwen
S
Department of Otolaryngology-Head and Neck Surgery, Baltimore, Maryland 21287, USA.
Best
Simon R
SR
Hung
Chien-Fu
CF
Loyo
Myriam
M
Lyford-Pike
Sofia
S
Flint
Paul W
PW
Tunkel
David E
DE
Saunders
John R
JR
Wu
T C
TC
Pai
Sara I
SI
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D005434:Flow Cytometry; D052140:Human papillomavirus 11 / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008285:Major Histocompatibility Complex / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D030361:Papillomavirus Infections / Q000276:immunology*; D019444:Vaccines, DNA / Q000276:immunology*
D019444:Vaccines, DNA; D007371:Interferon-gamma