Since its emergence in 1981, the HIV/AIDS pandemic has exerted a major toll on humanity with 39 million deaths worldwide. In 2016, 39.7 million people were infected with HIV, 1 million died and about 1.8 million were newly infected. Despite decades of research, there is no cure or vaccine; anti-retroviral therapy (ART) that suppresses viral replication remains the only option to prevent the outbreak of AIDS and death.
HIV poses a considerable challenge for developing a cure or vaccine as the virus inscribes its genome into the DNA of immune cells where it can stay quiescent for months or years. This reservoir of infected cells–that are invisible to the immune system–causes persistent infection that slowly depletes the immune system to cause AIDS and eventually death. A major focus of research is therefore on developing vaccines to prevent infection and on destroying the reservoir to cure the disease.
In his keynote talk, Nelson Michael reviewed the results from vaccine trials including the Ad26/MVA vaccine to treat both acute and latent infection. Animal studies showed that early treatment with this vaccine in combination with ART can drastically reduce acute infection. Ad26/MVA is now being tested for so-called ‘kick and kill' latency reversal therapies that awaken and destroy quiescent reservoir cells.
Louis Picker's presentation focused on the role of CD8+ immune cells in controlling cells infected with SIV (simian immunodeficiency virus, the animal precursor of HIV) and the efficacy of a RhCMV vaccine to treat acute and latent infection in nonhuman primates. Animal experiments showed that the vaccine creates a strong CD8+ immune response during early treatment, which is not enough, however, to destroy infected cells during latent infection.
Some patients develop broad neutralizing antibodies (bnAbs) that protect against a wide variety of viral strains and mutations. William Schief's group attempts to generate such bnAbs through sequential vaccination with engineered forms of the viral envelope protein.
Michael Farzan presented their work on engineered proteins that block HIV from entering its target cells. They use a viral vector to transfer the gene encoding the engineered protein into muscle cells to enable its sustained production.
David Margolis described the results of kick and kill approaches by which quiescent infected cells are repeatedly activated with the aim of reducing the viral reservoir. Studies in patients showed promising results, but it will require new approaches to better stimulate immune cells to attack active, infected cells.