Innovative New Approaches to Designing HIV Vaccines
By Jeffrey Laurence, M.D.
Published September 15, 2014
There are two major issues impeding HIV vaccine development. One relates to the rapid pace at which HIV replicates, making errors along the way. Those frequent mutations keep the virus several steps ahead of the body’s immune system and current vaccine candidates, preventing their ability to recognize and eliminate HIV. The second problem concerns the huge carbohydrate content of the surface of HIV, in particular the envelope protein. These sugars serve as a shield against immune recognition of the virus. This month, two amfAR-funded research teams report on their novel approaches to vaccine design, which may lead not only to better preventive vaccine candidates, but also to vaccines that could assist in a cure.
In August, we highlighted the work of Dr. Phillip Smith and his colleagues at the University of Alabama at Birmingham on mechanisms of HIV infection across penile and vaginal mucosa. Now, working with additional associates from the Czech Republic, Dr. Smith has expanded his research to examine how different carbohydrate patterns of the HIV envelope—formed as the virus grows in different cell types—can greatly impact virus recognition by different anti-HIV antibodies. Writing in AIDS Research and Therapy, he notes that about half of the surface that HIV presents to our immune systems is sugar. The sugar shield inhibits recognition of the virus in specific ways, which he could alter by chemical or genetic modifications to the viral envelope. Smith concludes that HIV surface structure is a critical consideration in vaccine design.
Dr. Douglas Nixon and colleagues from the University of California, San Francisco, George Washington University, University of Rochester, Oregon Health Sciences University, and the Montpellier Cancer Research Institute in France, explored a different approach. Reporting in the Journal of Immunology, the team sought to bypass problems inherent in targeting HIV by targeting a different set of viruses that are present in human cells as relics of our prehistoric past. These virus fragments, known as endogenous retroviral elements, specifically express their proteins on the surface of cells infected with HIV. They demonstrated in a test tube that by directing a vaccine's antibodies against those proteins, they were able to kill HIV-infected cells.
Nixon concludes that induction of such antibodies “may represent a novel approach in the quest to prevent and eradicate HIV-1 infection.” We certainly see their promise.
Dr. Laurence is amfAR’s senior scientific consultant.