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The potential of Ixolaris

SIV (simian immunodeficiency virus) is closely related to HIV. In some monkeys, SIV infection causes a syndrome similar to AIDS. Researchers sometimes use SIV-infected monkeys to conduct preliminary experiments with antiviral drugs and potential vaccines.

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In experiments with SIV-infected monkeys, researchers at the U.S. National Institutes of Health (NIH) and the University of Pittsburg, Pennsylvania, have found that SIV-infected cells of the immune system produce a protein called tissue factor (TF). This protein plays an important role in helping blood to form clots. In conditions where there is elevated inflammation, such as some cancers and HIV (and SIV) infection, there is an increased risk for blood clots forming. These can block vital blood vessels and cause heart attacks and stroke.

Monkeys

HIV treatment, also known as ART, works on monkeys with SIV because the viruses are so closely related. In experiments with SIV-infected monkeys, ART greatly reduced the amount of virus in their blood. However, a group of immune system cells called monocytes continued to produce excessive amounts of TF. In turn, elevated levels of TF seemed to drive inflammation by increasing the amount of the following chemical signals:

  • TNF-alpha (tumour necrosis factor-alpha)
  • IL-1b (interleukin-1beta)
  • IL-6 (interleukin-6)

Enter Ixolaris

The saliva of ticks that spread Lyme disease contains proteins that interact with the human immune system. One such protein is Ixolaris.

In lab experiments with cells of the immune system harvested from monkeys with SIV and humans with HIV, Ixolaris reduced the inflammatory effects of TF.

In another experiment, researchers infected eight monkeys with SIV and gave Ixolaris to five of them on the same day of infection. The Ixolaris-treated animals showed less inflammation and immune activation in their CD4+ and CD8+ cells. Furthermore, monocytes in the Ixolaris-treated animals had less TF compared to untreated monkeys. Also, Ixolaris-treated monkeys had reduced levels of another protein called D-dimer, elevated levels of which are associated with inflammation and excessive blood clot formation. These results with monkeys are interesting, but Ixolaris may have other benefits.

In the above experiments, monkeys were infected with an aggressive strain of SIV that causes the rapid development of an AIDS-like syndrome in as few as 100 days after infection. One of three SIV-infected monkeys not given Ixolaris developed AIDS in less than 100 days after SIV infection. In contrast, none of the Ixolaris-treated monkeys developed significant injury to their immune systems in that time.

Next steps

These experiments with monkeys have resulted in preliminary evidence about the potential of Ixolaris. The studies were small and not randomized or placebo-controlled, so their results are not definitive. A next step would be to test Ixolaris in a larger number of monkeys with SIV and conduct more complex and sophisticated immunological analyses. If such studies confirm the preliminary results of Ixolaris, researchers should then move forward and create purified Ixolaris under sterile conditions. This would be a minimum requirement prior to experiments with people.

Ixolaris is a protein with exciting potential but it will be several years before experiments in people begin. Still, the experiments with monkeys have helped scientists better understand how important immunological activation and inflammation are to the complex changes caused by SIV and HIV.

—Sean R. Hosein

REFERENCE:

Schechter ME, Andrade BB, He T, et al. Inflammatory monocytes expressing tissue factor drive SIV and HIV coagulopathy. Science Translational Medicine. 2017 Aug 30;9(405). pii: eaam5441.