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BETHESDA, MD— “In 1981, we were not at all prepared in the attitude at the time, and in the availability of responsible, qualified basic medical virologists. I was there. I know how people got involved, and it wasn’t by responsibility, but by chance.”
This is how Robert Gallo, MD, described the state of virology when AIDS first began making itself known to the medical community in the early 1980s. A former NIH investigator and the most referenced scientist in the world in the 1980s and 1990s, he is the only researcher to win two Laskar Awards, the second of which was for his work in determining that the HIV virus is the cause of AIDS. Currently, Gallo is director of the Institute of Human Virology at the University of Maryland School of Medicine.
Speaking on the campuses of NIH last month on the 25th anniversary of the creation of the HIV diagnostic kit, Gallo’s view of science’s prospects in regards to combating HIV is not so much cautious optimism, but a kind of hard-nosed realism. Gallo believes that the hurdles to stopping HIV might be greater than we think, but he expresses faith that mankind has the ability to reach that goal.
Tactics for Stopping HIV
“The needs for the future are continuing research on new therapeutic approaches, bringing therapy to those in need, and ultimately eliminating HIV,” Gallo declared. “We’re running major programs through Africa and parts of the Caribbean, but it’s still insufficient. Our institute is involved in treating around 600,000 people in Africa, and 5,500 in Baltimore, but I don’t know if it can be sustained. It’s extremely expensive, and it’s still not sufficient. A cure and/or eliminating HIV is necessary.”
There are a number of tactics that are being employed to that end. The first is disseminating HIV education. “Everybody would say that’s necessary, but surely it’s insufficient,” Gallo said.
Another tactic is the use of microbicides. “Recent positive results in South Africa suggest this will be helpful. But the caveats in my mind are that they could lead to drug resistant variants. I know some people are combining existing drugs to make them better, so that won’t be a problem. But the study was in an environment with medical experts. That won’t be routine in the future.”
A lack of close medical supervision concerns Gallo, and he worries that drug resistant variants of the virus would be the result.
Another therapy is chemoprevention—a concept getting increased attention over the last couple of years with the targeting of at-risk populations. While it can be an expensive enterprise, Gallo believes it will meet with some success. “I think it’s important, and it’s rightfully being pushed by NIH,” Gallo said.
Vaccine as Ultimate Solution
At the end of the day, the ultimate solution remains a viable HIV vaccine. While many scientists point to the hyper variability of the virus as being the primary hurdle in creating a vaccine, Gallo contends that variation is a solvable problem. “The real difficulties are that it’s a retrovirus. A few days after infection it will integrate its DNA so infection is immediately established. And very quickly it harms the immune system.”
To Gallo, this means that the main goal of a vaccine is sterilizing immunity or something very close to it. “For me a vaccine only based on cell-mediated immunity will never work,” he explained. “It’s useful to have it. It’s useful to see what happens. But it could never be an answer in and of itself alone. I believe we have to stop it at the gate. We need to block the virus entry or kill newly infected cells as they emerge.”
Any vaccine that does not create a sustained immune response will fail in trial, Gallo stated.
To create a sustained sterilizing immunity, any vaccine will require antibodies, Gallo explained. Those antibodies must target at least part of the envelope surrounding the virus. One of the best targets on the envelope is a particular glycoprotein—gp120—on the exposed envelope surface.
A study published by Gallo a year ago looked at an analysis of a group of HIV-infected patients who control the virus without therapy—elite controllers. An examination of their blood found no interesting sera antibodies. The investigators looked at memory B cells in the patients, and they found these cells were producing a large amount of antibodies that specifically react to gp120 bound to CD4—host cells that aid HIV in replication.
Some of those antibodies had a direct effect on antibody-dependent cell-mediated cytotoxicity—a mechanism through which antibodies limit and contain infection.
“We suggest that these antibodies blunted early infection,” Gallo stated. “We support a candidate vaccine using CD4 antibodies.”
While the road to developing a vaccine for HIV will likely be paved with many failures, they are failures that can and must be overcome, because HIV will not be going away on its own. “Viruses are forever,” Gallo declared. “Globalization narrows the world, not only politically, culturally, and genetically, but also the microbial world. And though we have seemingly adequate epidemiologists and public health people, there is a need for assurances that there is a continuous pool of responsible expert basic laboratory virologists that cover the full gamut of known pathogenic viruses.”