AIDS Vaccine 2001 Conference Optimistic Over Vaccine Progress, New Vaccine Candidates, But Success in Monkeys May Not Translate to Humans
The AIDS Vaccine 2001 conference opened in Philadelphia on Wednesday with a sense of optimism for the future of vaccine research, the Philadelphia Inquirer reports. Five years ago, the quest for a vaccine against HIV was "going nowhere," but now, buoyed by an influx of money, researchers predict a human vaccine is possible. "This meeting is a celebration of the fact that we now have a huge pipeline. We went from a cottage industry ... to today having a worldwide effort on many different fronts," David Baltimore, a leading AIDS researcher and conference organizer, said, adding, "I'm optimistic in a way I wasn't a couple of years ago." The development of an AIDS vaccine is "uniquely challenging" because the virus mutates quickly and directly attacks the immune system. Further complicating matters, humans do not develop a natural immunity to HIV like they do to some other diseases (McCullough, Philadelphia Inquirer, 9/6). According to Baltimore, researchers have learned that approaches that seek to neutralize antibodies "don't work very well," but that stimulating the killer T-cells of the immune system may produce an immune response sufficient to keep the virus under control. Scientists must now determine how to elicit that response and "how to keep these cells going," he added (Mitchell, Reuters Health, 9/6).
Reason For Optimism
The success of several vaccine trials in monkeys is the biggest reason for the optimistic mood at the conference, according to the San Francisco Chronicle. Yesterday, researchers from Yale University School of Medicine presented findings, also published in today's edition of the journal Cell, that a vaccine using vesicular stomatitis virus (VSV) as a delivery agent for HIV proteins has protected for 14 months seven rhesus monkeys that were exposed to SHIV, a hybrid simian version of HIV. Seven out of eight control monkeys developed AIDS-like symptoms and were euthanized. The Yale vaccine is of particular interest because it is delivered in a single dose by nose spray or drops, an approach that would make it a good candidate for the developing world. The vaccine is also relatively inexpensive to manufacture, with a liter of concentrated starting material possibly being sufficient to produce enough vaccine for one billion people. Human trials are not yet planned, and there is "no direct evidence that the approach will work in people" (Hall, San Francisco Chronicle, 9/7). There is also some concern over the use of VSV, a live virus that can cause a flu-like disease in animals. But lead study author John Rose noted that some people in South and Central America carry the virus but have never shown signs of any "serious" illness. "This situation also suggests that the (weakened [virus] vaccine) employed here will be nonpathogenic in humans," he added (Reuters Health, 9/6). The intellectual property rights for the vaccine were acquired by Wyeth Lederle Vaccines, a unit of American Home Products Corp., for an undisclosed amount (Schoofs, Wall Street Journal, 9/7).
Harvard Vaccine Also Protects Monkeys
Another vaccine trial, conducted by researchers at Harvard Medical School, also was presented at the conference. Researchers injected monkeys with a vaccine containing a piece of DNA that held the codes for two HIV genes. They also injected the monkeys with the gene for interleukin-2, a "hormone-like substance that helps stimulate immunity," and then exposed them to SHIV. After almost two years, all of the vaccinated monkeys are alive and well with normal CD4+ cell counts, while 75% of the control monkeys that had been exposed to the virus died (Brown, Washington Post, 9/7). "After 600 days there is no evidence of disease, no evidence of rebounding virus. This is all good news," Dr. Norman Letvin said (AP/Baltimore Sun, 9/7). Preliminary results from a human trial of the first vaccine developed specifically to fight the HIV strain most common in Africa were also presented. Testing in a small group of patients produced a "strong immune response," Mitalu Mwau of the University of Oxford, which is overseeing the trials in the United Kingdom and Kenya, said. The group hopes to begin additional trials next year (Silverman, Newark Star-Ledger, 9/7).
Translating Primate Success to Humans
The excitement over the success of primate vaccine trials "may rest on rocky, even dangerously misleading, science," Newsday reports. Dr. Ronald Desrosiers, director of the New England Primate Research Center, said that the enthusiasm is "totally astounding, to the point of being irresponsible, in many cases." Desrosiers said that the problem with all of the primate vaccine studies is that researchers challenge the vaccine candidates in monkeys using SHIV, a "super-lethal artificial monkey AIDS virus." The virus is different from the naturally occurring simian immunodeficiency virus because it "obliterate[s]" CD4+ cells within weeks, much faster than the natural virus. Scientists said that the rapidity with which the virus moves is necessary for research that would otherwise take many months and even years to show results. But Desrosiers and others argued that the virus is too different for the results to be applicable to humans. "It's a cloned (artificial) virus, it rapidly kills off CD4+ cells. I think it's an open question, and I think it would be a mistake to assume too much," Dr. Gary Nabel, director of NIH's Vaccine Research Center, said. The virus also attaches to CXCR4 receptors on the surface of immune cells instead of the CCR5 receptors used by HIV. Vaccine researcher John Moore of the Weill Medical College of Cornell University said that there is "no good reason" to use a virus that operates on different receptors. "You're looking at an aberrant situation. I think the best of the vaccine concepts are going to do okay against other challenge viruses, but there are too many vaccines that are doing too well against the SHIV virus that don't work against SIV," he added (Garrett, Newsday, 9/5).
Not So Fast
Although the overall tone of the conference was one of optimism, researchers admitted there was still cause for concern. "There is a danger of things slowing down, because it is such an arduous process. And this is like the half-way point in a marathon: The worst part may be yet to come," Dr. Beatrice Hahn of the University of Alabama-Birmingham said. Baltimore conceded that the meeting was "only a beginning" and added that it should be seen "hopefully as the beginning of the end." In addition, the vaccine industry has had trouble attracting and retaining top talent. To bolster research efforts, the U.S. government recently raised post-doctorate fellowship starting salaries from $25,000 to $45,000. It also plans to raise vaccine spending to $357 million in the next fiscal year. However, any vaccine will not help those in the developing world if the "challenges posed by politics, the demand for profits and a lack of infrastructure" are not dealt with, Reuters reports. "Our science will produce an AIDS vaccine before our humanity figures out how best to use it," Dr. William Foege, a senior health adviser to the Bill and Melinda Gates Foundation, said (Morgan, Reuters, 9/6).
Speaking for Africa
Conference attendees on Wednesday also heard from Rwandan President Paul Kagame. Currently, roughly 10% of Rwandans are infected with HIV and between 10,000 and 15,000 infants contract the virus from their mothers each year. Although Kagame cited the need for a vaccine, he said that the "primary responsibility of controlling HIV/AIDS in Africa lies with Africans," adding that "internal leadership and political will" are needed to successfully battle the epidemic. His nation's infection rate has stabilized through condom campaigns and "other behavioral interventions," and a 10-fold increase in HIV screening is expected to help prevent 5,000 to 7,000 cases of vertical transmission each year, he added (Reuters Health, 9/6).