HIV-1 Protease Has a Genetic T-Cell Adjuvant Effect Which Is Negatively Regulated by Proteolytic Activity

Abstract

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 chaperonelike 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 chaperonelike 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 chaperonelike activity and negatively by its proteolytic activity.

Mtb32 is a promising tuberculosis antigen for DNA vaccination in pre- and post-exposure mouse models

“…29 Additionally, the inactivated HIV-1 protease acts as a strong T-cell adjuvant for genetic vaccines exerting an antitumor effect in a HPV cancer mouse model. 30 It is suggested that antigens expressed during the first phase of growth initially provide protection against M. tuberculosis infection, whereas those expressed during the late stages help to prevent reactivation of the disease. 4 The protective effects of early secreted culture filtrate proteins, including ESAT-6, TB10.4, Ag85A and Ag85B, are well established.…”