Atomic-Scale Pictures Show Chink in HIV’s Amour
Researchers have delivered a rare piece of good news in the struggle against AIDS, saying they have identified an area of the human immunodeficiency virus (HIV) that revives hopes for an antibody-based vaccine.
Mutating and slippery and with several lines of defense, HIV has been the most formidable foe that vaccine designers have ever faced.
Attempts to engineer a classic preventive vaccine that stimulates antibodies – the first line of the body’s defenses – have been thwarted by the virus’ swift and constant genetic switches.
This daunting, shape-shifting ability means that an antigen, a piece of the virus that is used to prime antibodies, is out of date by the time these defenders encounter a real-life viral intruder.
HIV also has a cloak of sugary molecules that prevents antibodies from slipping in and blocking the virus from docking onto an immune cell, the first step towards infecting it.
These were among the problems to explain the frustrating failure of AIDSVAX, the only prototype vaccine that has gone through the long and costly three-phase process of tests for safety and effectiveness.
After this setback, researchers in AIDS vaccines almost gave up on antibodies. The big focus today is on priming T cells, the body’s heavy weaponry, to recognize and destroy the virus, which arguably makes it less a vaccine and more a treatment.
But a US team, reporting in the British journal Nature, say they have taken an atomic-scale snapshot of a key location on the tip of the virus’ docking spike, called glycoprotein 120 (gp120), that is stable and unmutating – in other words, a fixed target.
Even better, this location on gp120 is recognized by a specific antibody, called b12, found in the blood of people who are able to hold the virus at bay for long periods.
By latching onto a virus, an antibody can neutralize it. In plain language, it’s like putting a piece of chewing gum on the tip of a key to prevent it from fitting into a lock. Antibodies also alert the rest of the immune system to come and destroy the germ.
Elias Zerhouni of the US National Institutes of Health (NIH), which oversees the National Institute of Allergy and Infectious Diseases (NIAID) where the work was carried out, said the paper showed “a gap in HIV’s amour.”
“One of our primary goals is to develop HIV vaccines that can stimulate broadly neutralizing antibodies,” said Gary Nabel, a co-author of the paper.
“The structure of this gp120 epitope [recognition site], and its susceptibility to attack by a broadly neutralizing antibody, shows us a critical area of vulnerability on the virus that we may be able to target with vaccines.
“This is certainly one of the best leads to come along in recent years.”
AIDS, a condition in which the immune system is so wrecked that the body becomes prey to opportunistic disease, was recognized in 1981. It has since killed more than 25 million people. Almost one percent of the world’s population today has been infected by HIV, which causes AIDS.
Wayne Koff, a top scientist at the International AIDS Vaccine Initiative, which co-sponsored the research, said promising new paths had been opened up in an arduous quest.
“This work uncovers a potential HIV vulnerability that provides an important direction for the design of novel vaccine concepts,” Koff said.
“(It) is further evidence that an effective, preventive AIDS vaccine is possible.”Filed under: Health