Tricky virus thwarts scientists efforts

BY DELTHIA RICKS | Newsday Staff Writer

June 4, 2006

Few scientific pursuits have proved quite as vexing as the decades-long search for a vaccine to guard against infection with HIV.

Many of the reasons behind the lack of a protective vaccine boil down to the complex nature of the virus itself.

Structurally, HIV is equipped with moving spikes and a thick coating of sugar molecules that enable it to dupe and destroy the human immune system. People infected are quickly swarmed by a virus that replicates at warp speed by hijacking its host's genes. And HIV mutates at such a clip, an individual can be infected with multiple, genetically distinct viruses, even drug-resistant ones, readily passed to another person.

Worse still, HIV homes in on the CD-4 T cell, the very constituent that helps orchestrate the immune response.

"This virus is a moving target, a diverse moving target. If there was a vaccine that worked against one variant, it might not protect against another," said Dr. Michael Gottlieb, the Los Angeles immunologist who first described AIDS symptoms in June 1981.

Scientists have tried dozens of approaches since the virus itself was identified in 1983. But many of the earliest attempts, based on traditional vaccine techniques, didn't work. In the past 20 years, there have been 94 HIV vaccine trials involving 20,000 people in the United States and abroad.

"This virus thwarts efforts at designing drugs and vaccines," said Dr. Fred Valentine, director of NYU's AIDS Research Center.

Only now do scientists think they're breaking ground on potential products. Vaccine developers have embarked on studies that borrow from gene therapy, a technique being exploited for several forms of cancer and rare genetic diseases. The idea is to get a vaccine molecule directly into human genes where HIV prefers to reside.

Last year, the United States spent more than 20 percent of its $3 billion AIDS research budget on vaccine and drug projects.

A candidate vaccine developed by Merck Inc. and another designed by scientists at the National Institute of Allergy and Infectious Diseases rely on vectors, molecular vehicles that shepherd vaccine molecules into human DNA. The Merck vaccine uses a deactivated adenovirus to integrate its vaccine cargo into human genes. Adenoviruses, when active, can cause the common cold.

Government scientists, meanwhile, have developed an avipox vector, a modified and deactivated smallpox virus, chosen because it efficiently insinuates itself into DNA. Even with such bold technology, experts say an effective HIV vaccine is many years away.

"HIV is in a category by itself," said Dr. Peter Palese, chief of microbiology at The Mount Sinai Hospital in Manhattan. "It is separate from other viruses when it comes to making a vaccine. HIV gets integrated into the human genome, and it can hide in the body. Other viruses do not become part of you" as HIV does.

HIV is a retrovirus, an insidious pathogen whose heritable information is stored in the genetic material known as RNA. Internally, HIV contains an enzyme allowing it to translate its RNA into DNA, using its host's cells like infinitesimal photocopying machines to make millions of new viruses.

Dr. Gary Nabel, director of vaccine research at the National Institute of Allergy and Infectious Diseases in Bethesda, Md., agreed that HIV's ability to escape immune-system detection has been a formidable obstacle. Thus the importance of producing a high-tech vaccine that integrates into human DNA, he said.

"Normally when you make a vaccine, the immune system homes in on proteins on the viral surface. But this virus covers its surface with sugar molecules, so you have this sugar-coated virus, and sugars do not look foreign to our immune system," Nabel said.

Experts cite another major obstacle: "The patient is infected with a swarm of viruses," Valentine said. Because of HIV's tendency to swarm, a mind-boggling number of viruses are continuously produced.

Nabel estimates there can be more AIDS viruses in an infected individual than there are influenza viruses in global circulation at the height of flu season. As for a vaccine due date: "The best-case scenario is five to 10 years from now. That's how long it takes to do the proof of concept trials. And at that time, I would love to say it worked. But I'm not holding my breath," Nabel said.