CMV-based vaccine can clear SIV infection in macaques Could a vaccine be used to functionally cure HIV infection? New evidence from an animal study suggests the strategy may work, though the infection cleared was—of course—of simian immunodeficiency virus (SIV), not HIV. We have previously reported that Louis Picker of Oregon Health & Science University and his colleagues found that half of rhesus macaques vaccinated with a cytomegalovirus (CMV) derived vector encoding SIV genes could suppress viral load to undetectable levels after repeat rectal challenge with SIV (Nature 473, 523, 2011). This effect is likely due to the induction of an unusual and broad effector memory T cell response (Science 340, 940, 2013). In a new study (Nature 2013, doi:10.1038/nature12519), the group shows that the vaccine suppresses SIV to undetectable levels in about half the animals after vaginal and intravenous challenge as well. This suggests that the immune response elicited by the vaccine is not restricted to mucosal tissues—the soft lining of body cavities, where SIV and HIV establish infection—but can also control viral load in the blood. What’s more, by 70 weeks after rectal challenge, vaccinated animals had no remnants of SIV DNA or RNA, or replication-competent SIV, in blood or tissues. Even extremely sensitive assays failed to detect any virus, though the animals previously had detectable virus in blood and tissues. This suggests that the effector-memory T cells induced by the vaccine progressively eliminated all infected cells, including SIV reservoirs in latently infected cells. One possible explanation for the clearance of latently infected cells is the observation that such cells sometimes start expressing HIV proteins in a random fashion. It’s possible, Picker says, that the vaccine-induced T cells target and eliminate such cells. In principle, this type of vaccine could be used alone or together with other cure strategies that are designed to eradicate viral reservoirs, Picker says. He cautions, however, that the reservoir in most people on HAART is likely larger than the reservoir in his CMV-vaccinated macaques. “That’s probably a higher bar,” he says, adding that it might therefore take much longer to clear HIV infections in people on HAART than the 1-2 years it took to clear SIV infection in his macaques—especially in people who start ART during chronic infection. “It may well be that in humans that are put on ART well into their plateau phase, the rate at which those latent cells express HIV antigens may be such that it would take ten or 20 years to clear their reservoir,” Picker says. That’s why additional treatment with agents that activate HIV production in latently infected cells might be needed to accelerate the process, he adds. To test if such an approach might work, Picker plans to treat SIV-infected rhesus macaques with HAART until they have undetectable viral load, and to then vaccinate them with his CMV-based SIV vaccine. He would then treat them with agents that activate HIV expression in latently infected cells (such as HDAC inhibitors) and check if the CMV-vaccine induced immune response can eliminate these reactivated cells, so that the animals would not have any rebound in viral load even after stopping HAART. “We are hoping to do that study in monkeys,” Picker says. “That’s the next experiment in terms of proof of principle.” Written by Andreas von Bubnoff iavireport.org/Blog/archive/2013/09/13/cmv-based-vaccine-can-clear-siv-infection-in-macaques.aspx
Posted on: Tue, 06 Jan 2015 14:21:46 +0000
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