In a study published online today (02/18/15) in the prestigious journal Nature, a team of researchers from across the US have shown complete effectiveness of a new vaccine against simian immunodeficiency virus (SIV) and multiple versions of human immunodeficiency virus (HIV).
The researchers began injecting macaque monkeys 40 weeks ago with a vaccine called eCD4-Ig. Unlike other vaccines, eCD4-Ig combines protein epitopes with antibody sensitivity to block the capability of SIV and HIV from binding to a cell.
The proteins are also delivered via an adenovirus packaging system. As the harmless adenovirus enters cells, it coopts the cell machinery to begin producing virally encoded proteins. While this technique is similar to HIV, adenoviruses do not stop normal cellular processes. As the cell produces its needed proteins, it also produces the eCD4-Ig molecules, which eventually get released into the circulation.
Env, a highly conserved binding domain on the viral surface, allows the virus to attach to the CCR5 receptor on CD4+ T cells. When the virus attaches to CCR5, an irreversible reaction cascade occurs that tightly binds the virus to the cell and develops a pore for injection of viral RNA. The researchers hypothesized that if they could fool the virus into thinking it was binding to the cell, and thus initiate the binding cascade, the virus would be rendered useless.
The researchers were able to show the macaques had high enough eCD4-Ig titers to render them resistant to SIV, HIV-1 and HIV-2 through this protein binding mimic. The resistance lasted at least 40 weeks, when the study was published, and protected the monkeys from 8- to 16-times the infectious dose of virus. Further results will show whether vaccine boosters are needed as titers get lower, and whether this vaccine protects individuals with chronic infections from succumbing to dangerously low immune cell counts.
“Unlike antibodies, which fail to neutralize a large fraction of HIV-1 strains, our protein has been effective against all strains tested, raising the possibility it could offer an effective HIV vaccine alternative,” said study leader Michael Farzan, a professor at the Scripps Research Institute in Florida. Indeed, previous studies using antibody-based vaccines have run into issues as the HIV virus mutates around the protection.
Farzan continues hopefully, “This is the culmination of more than a decade’s worth of work on the biochemistry of how HIV enters cells. When we did our original work on CCR5, people thought it was interesting, but no one saw the therapeutic potential. That potential is starting to be realized.”
