A novel HIV vaccine targeting the protease cleavage sites
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Li et al. AIDS Res Ther (2017) 14:51 DOI 10.1186/s12981-017-0174-7
Open Access
REVIEW
A novel HIV vaccine targeting the protease cleavage sites Hongzhao Li1†, Robert W. Omange1†, Francis A. Plummer1,2 and Ma Luo1,2,3*
Abstract HIV preferentially infects activated CD4+ T cells and mutates rapidly. The classical vaccine approach aimed to gener‑ ate broad immune responses to full HIV proteins largely failed to address the potential adverse impact of increased number of activated CD4+ T cells as viral targets. Learning from natural immunity observed in a group of HIV resistant Kenyan female sex workers, we are testing a novel vaccine approach. It focuses immune response to the highly con‑ served sequences surrounding the HIV protease cleavage sites (PCS) to disrupt viral maturation, while limiting exces‑ sive immune activation. Our pilot studies using nonhuman primate SIV infection models suggest that this approach is feasible and promising. Keywords: HIV, Vaccine, Protease cleavage sites, Natural immunity, Pumwani sex worker cohort, Nonhuman primate, SIV Background Worldwide, it is estimated that almost 37 million people are living with human immunodeficiency virus type 1 (HIV-1). In 2015 alone, around 2.1 million individuals became newly infected with HIV and 1.1 million people died from AIDS, highlighting the urgent need for an effective HIV vaccine. Six HIV vaccine candidates to date have been tested in Phase IIb clinical trials. The first two trials Vax004 and Vax003 sought to induce protection by eliciting antibody responses to gp120, but failed to protect against HIV acquisition [1, 2]. The three other phase IIb trials, HVTN502, 503 and 505, attempted to induce T cell-based immunity against HIV. All three failed to elicit immune responses capable of providing protection against HIV acquisition [3–5]. The only HIV vaccine that has been modestly successful was from the RV144 trial, in which a recombinant canary pox-based vaccine (ALVAC) combined with a recombinant gp120 (AIDSVAX) vaccine was tested. The vaccine protected 31% of vaccinees against HIV acquisition after a modified intention-to-treat analysis [6]. *Correspondence: ma.luo@phac‑aspc.gc.ca † Hongzhao Li and Robert W. Omange contributed equally to this work 3 JC Wilt Infectious Diseases Research Center, National Microbiology Laboratory, 745 Logan Avenue, Winnipeg, MB R3E 3L5, Canada Full list of author information is available at the end of the article
HIV primarily infects CD4+ T cells, a critical component of the human immune system. As a retrovirus HIV mutates rapidly, giving rise to extensive genetic diversity. These inherent characteristics underscore the challenges for developing a prophylactic vaccine. Novel approaches and ideas need to be tested to develop an effective vaccine to HIV-1.
Natural immunity to HIV: a new clue to vaccine development Edward Jenner developed the successful smallpox vaccine based on the natural immunity observed in milkmaids. Thus, the correlates of natural immunity to HIV-1 documented in highly exposed uninfected
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