It’s Not All Gloom on the AIDS Front

Advances are clearly proving hard — but hardly impossible — to come by. Lots more funding sure would help, though.

Advances are clearly proving hard — but hardly impossible — to come by. Lots more funding sure would help, though. Stemming the scourge of acquired immune deficiency syndrome (AIDS) has been one of the most daunting challenges of the last two decades. Early on, researchers realized that the human immunodeficiency virus (HIV) was unlike any other — virulent and highly resistant to treatment or cure. And almost from the beginning, scientists and public-health advocates insisted that an AIDS vaccine would be the key to ending the disease’s spread.Twenty three years after the first AIDS cases began to appear, the quest for a safe, effective vaccine is still aching for a breakthrough. At the same time, the disease keeps expanding its reach and is already a pandemic of global proportions. In total, 40 million people are now living with AIDS worldwide. Some 14,000 people are infected with HIV daily. Various antiviral treatments can control disease, but they’re out of reach for most of the Third World, where the burden is heaviest.Indeed, at the 15th annual International AIDS conference in Bangkok in mid-July, vaccine proponents pointed out that adequate spending and cooperation in the field remain lacking. Other obstacles cited include limited drug-manufacturing capacity and a too-narrow scientific focus.CONTINUING SEARCH. To date, news about AIDS vaccine research has been mostly disheartening. The only vaccine candidate to be tested so far in broad human trials failed to pass muster: Last year, after 15 years, two large trials, and $130 million, a vaccine knows as Aidsvax made by biotech VaxGen fell short of study goals.Yet despite the Aidsvax disappointment and the many other scientific and logistical challenges, the search continues in earnest. The International AIDS Vaccine Initiative (IAVI) points out that the number of small-scale vaccine trials in humans has doubled to 30 since 2000. The HIV Vaccine Trials Network, once lacking vaccine candidates ready for human testing, has seen its study centers fill up in recent years.True, the amount spent by industry and academia on AIDS vaccine research is a pittance compared with funding for scads of more profitable and less daunting medicines. However, researchers say the field is robust. “We’re at a point where there’s a lot of information,” says Emilio Emini, vice-president and chief of vaccine development at IAVI. “Columbus had a strong feeling but didn’t know how far it was to land. It’s the same with AIDS vaccines.”WILY VIRUS. A viable AIDS vaccine is no doubt still many more years away. But scientists remain optimistic. “Some people are very gloomy about it, but I’m not,” says Harriet Robinson, chief of microbiology and immunology at Yerkes Primate Center at Emory University and a member of the Emory Vaccine Center. “There has been very good progress.”The drug industry, Robinson notes, is becoming more interested in the field, as the “path to products is becoming more apparent.” The world’s major vaccine makers — Aventis (AVE ), GlaxoSmithKline (GSK ), Chiron (CHIR ) and Merck (MRK ) — all have active, though early-stage, AIDs programs.Certainly, plenty of obstacles remain to be overcome. Antiviral drugs can control the scale of infection, but the AIDS virus is wily, and it finds ways to prevent the immune system from completely eliminating it. The goal, Emini says, is to “develop a vaccine that will teach the immune system to do what it does better, so that once an infection occurs, there will be a suitable response.”FULL-COURT PRESS. To that end, vaccine researchers have focused on three main approaches. The first, like Aidsvax, are vaccines aimed at getting antibodies to neutralize the virus. A second group focuses on stimulating infection-fighting cells called T-cells. Third are vaccines that aim to spur both kinds of responses — T-cells and antibodies.Among the most advanced vaccines is Merck’s, which uses the third tactic and will begin Phase 2 human testing before yearend. “We’re throwing as many antigens at the virus as we can,” says Jon Condra, senior HIV investigator at Merck. The vaccine will use common-cold viruses as the carrier for three different pieces of HIV that covers 50% of an HIV cell’s surface. Those three pieces of HIV will then stimulate the immune system. Says Condra: “By far, these proteins elicit the strongest immune responses.”Emory University’s Robinson is also working on an AIDS vaccine targeting the same three HIV proteins, but it uses a slightly different way to deliver the proteins to the immune system. She expects to begin a Phase 2 trial in the second quarter of 2005. Overall, Robinson expects that these latest vaccines will do better in humans than they have in animals.ACCEPTING FAILURE. VaxGen’s Aidsvax isn’t completely dead either. Aventis has paired its vaccine Alvac, which uses weakened canarypox virus to deliver components of HIV, with Aidsvax. A late-stage trial of this combination is ongoing in Thailand.Don Francis, founder and former chief of VaxGen, wants to figure out where Aidsvax went wrong. The vaccine was able to protect chimps from the virus, but the beneficial effects didn’t transfer to humans. “Our goal is to leverage data out of the Phase 3 trial of Aidsvax,” says Francis, who now runs Global Solutions for Infectious Disease, a new nonprofit organization aimed at developing vaccines for AIDS and other diseases for the developing world.Certainly, AIDS vaccine research is painfully slow-going, and the future is sure to be fraught with pitfalls. “We have to be willing to accept a lot of failures,” Emini says. Considering that scientific interest in the area remains strong, increased financial commitments from governments, academia, and industry would go a long way toward bringing an AIDS vaccine within grasp. And that’s reason for encouragement, not discouragement. (Source: Buisness Week, July 2004)