Protein Delivered By Gene Vector May Protect Against HIV-Like Viruses

Dr. Michael Farzan PhD Vice Chairman Department of Immunology and Microbial Science Florida Campus The Scripps Research Institute MedicalResearch.com Interview with:
Dr. Michael Farzan PhD
Vice Chairman
Department of Immunology and Microbial Science
Florida Campus
The Scripps Research Institute

Medical Research: What is the background for this study?

Dr. Farzan: The key points are that HIV-1 needs two receptors – CD4 and CCR5 – to infect cells. CD4’s primary job is to initially bind the viral entry protein, which upon CD4 binding, uncloaks its CCR5 binding site. A number of years ago we observed that CCR5 had an unusual modification that was really important to HIV-1. We later showed that antibodies – protein your body makes to protect from pathogens – mimics CCR5 by incorporating this modification. We develop a peptide from one of these antibodies that mimics CCR5.

Medical Research: What are the main findings?

Dr. Farzan: By combined a soluble form of CD4 with this CCR5-mimicking peptide, we created a protein that neutralizes all HIV-1 isolates tested, including the hardest-to-stop viruses, as well as distantly related viruses found in monkeys. It does so better than the best HIV-1 antibodies. We expressed this protein using a commonly used gene-therapy vector, and showed that after a one-time inoculation we could protect from doses much higher than most humans are likely to see, and we did so 34 weeks after the inoculation.

Medical Research: What should clinicians and patients take away from your report?

Dr. Farzan: Our compound is the broadest and most potent entry inhibitor thus far described. It has the additional advantage that it is less immunogenic and more difficult to escape than antibodies. When delivered with a gene therapy vector, it can protect animals from high doses of an HIV-like virus administered intravenous in rhesus macaques. More generally it opens the possibility that long-term protection from the virus, or even long-term suppression, may be possible after a single injection.

Medical Research: What recommendations do you have for future research as a result of this study?

Dr. Farzan: We need to better understand the conditions where our compound might be useful as a therapy. We also need to optimize delivery of our compound, and improve systems from regulating its expression.

Citation:

AAV-expressed eCD4-Ig provides durable protection from multiple SHIV challenges

Matthew R. Gardner, et al

Nature (2015) doi:10.1038/nature14264 Published online 18 February 2015

MedicalResearch.com Interview with: Dr. Michael Farzan PhD (2015). Protein Delivered By Gene Vector May Protect Against HIV-Like Viruses

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