HIV-1 protease has a genetic T-cell adjuvant effect which is negatively regulated by proteolytic activity.
HIV protease (PR) mediates the processing of human immunodeficiency virus (HIV) polyproteins and is necessary for the viral production. Recently, HIV PR was shown to possess both cytotoxic and chaperone like activity. We demonstrate here that HIV PR can serve as a genetic adjuvant that enhances the HIV Env and human papillomavirus (HPV) DNA vaccine-induced T-cell response in a dose-dependent manner, only when codelivered with DNA vaccine. Interestingly, the T-cell adjuvant effects of HIV PR were increased by introducing several mutations that inhibited its proteolytic activity, indicating that the adjuvant properties were inversely correlated with its proteolytic activity. Conversely, the introduction of a mutation in the flap region of HIV PR limiting the access to the core domain of HIV PR inhibited the T-cell adjuvant effect, suggesting that the HIV PR chaperone like activity may play a role in mediating T-cell adjuvant properties. A similar adjuvant effect was also observed in adenovirus vaccine, indicating vaccine type independency. These findings suggest that HIV PR can modulate T-cell responses elicited by a gene-based vaccine positively by inherent chaperone like activity and negatively by its proteolytic activity.
Kim
Kwang Soon
KS
Cellular Immunology Laboratory, Division of Molecular and Life Science, Postech Biotech Center, Pohang University of Science and Technology, Pohang, Republic of Korea.
Jin
Dong Bin
DB
Ahn
So Shin
SS
Park
Ki Seok
KS
Seo
Sang Hwan
SH
Suh
You Suk
YS
Sung
Young Chul
YC
D016915:AIDS Vaccines / Q000235:genetics / Q000276:immunology*; D000276:Adjuvants, Immunologic / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D005260:Female; D016333:HIV Protease / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D020125:Mutation, Missense; D053918:Papillomavirus Vaccines / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology*
D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D053918:Papillomavirus Vaccines; D019444:Vaccines, DNA; D016333:HIV Protease; C514803:p16 protease, Human immunodeficiency virus 1