Gene Therapy Overcomes Vaccines in HIV Prevention
March 23, 2015
For the HIV cure and eradication session at CROI 2015, once again, the organizers were funny in choosing the title, "Leaky Latency." In general, all reports were bad news for HIV cure. The more we learn, the higher the distance seems to HIV eradication.
However, on the vaccine front, folks from Florida presented data on an engineered CD4 immunoadhesin (eCD4-Ig), which puts some light into an otherwise dark tunnel.
The group constructed a CD4-Ig with half of the ectodomain of CD4 in domains 1 and 2 fused to the human IgG1-Fc receptor. This was fused to a sulfopeptide CCR5 mimetic in the C terminus, which will bind both CCR5 and CXCR4 HIV. Finally, the group used an adeno-associated virus vector to deliver these eCD4-Ig -- and after all that technical jargon -- you might have an effective HIV vaccine alternative!
The researchers explored a panel of highly resistant HIV-1, HIV-2 and SIV in vitro against their eCD4-Ig and compared it to the best broadly neutralizing antibodies currently available. Their eCD4-Ig variant presented significantly lower IC50 values, in the nanomolar range (all IC50 < 1.2 μg/mL), and 100% of the isolates were fully neutralized while all the remaining comparators had a high number of viruses resistant to them. The titers in animals remained stable at 56 weeks at about 15-75 μg/mL, levels that would be fully suppressive.
Finally, the researchers exposed macaques to increasing doses of intravenous SHIV challenges. All four controls became infected, while none of four treated macaques became infected even after eight intravenous challenges. Science fiction? Well, we are far from using this strategy in humans, and proving effectiveness and safety will be a priority. It will not be easy to produce enough eCD4-Ig to use on a large scale, but so far, no results with vaccines have been as successful as this. There, in the race to HIV protection, gene therapy has overcome vaccines at CROI 2015.
Which other studies presented at CROI 2015 will have lasting impact? Read more of Llibre and Young's top picks.
Josep M. Llibre, M.D., is in the HIV Unit of the "Lluita contra la SIDA" Foundation at University Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain. Llibre has received funding for research or payment for conferences or participation on advisory boards from Abbott, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, Janssen-Cilag, Merck Sharp & Dohme, and ViiV Healthcare.
Benjamin Young, M.D., Ph.D., is vice president and chief medical officer of the International Association of Providers of AIDS Care based in Washington, D.C., and an adjunct professor at the Josef Korbel School of International Studies at the University of Denver. Young has received consulting or speaking fees from Bristol-Myers Squibb, Cerner Corporation, Gilead Sciences, GlaxoSmithKline, Merck & Co., Monogram Biosciences, and ViiV Healthcare. He has received research funding from Bristol-Myers Squibb Company, Cerner Corporation, Gilead Sciences, GlaxoSmithKline, Merck & Co., and ViiV Healthcare.
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