SUMMIT DAILY.com
The (Petri) Dish
ENLARGE
Last week, Summit County hosted an important conference on vaccines for
Human Immunodeficiency Virus (HIV). The conference attracted leading
scientists from around the world to share their latest research advances
and discuss future opportunities. The excitement at the meeting was
intense, as scientists believe they are finally making headway toward
developing a vaccine against this awful virus.
Our planet is in the midst of a raging HIV pandemic. The World Health Organization reports that more than 34 million people are infected with HIV, 10 percent of whom are children under age 15. HIV is taking its greatest toll in the developing world, with Africa and Asia being primary hotspots. In addition to killing about two million people every year, the virus also reduces resistance to other infectious diseases. In fact, HIV is driving a major resurgence of tuberculosis and newly emerging drug-resistant forms that pose serious global threats.
HIV is transmitted through sexual contact, blood transfer (e.g., shared needle use) or pregnancy and breastfeeding. The virus then sets up shop in white blood cells — the body's immune system — and a race begins between the virus, which kills white blood cells, and the body, which desperately manufactures new white blood cell replacements. For a while, a balance is achieved, but eventually the virus prevails and the white blood cell count drops. This immune system exhaustion results in a declining capacity to fight all types of infections — a condition referred to as Acquired Immune Deficiency Syndrome, or AIDS. Eventually, the infected individual succumbs to diseases normally shrugged off. Even the common cold becomes lethal.
In recent years, drug treatments have led to the control of HIV in the developed world. Although the drugs are expensive and have significant side effects, they can suppress the virus. The drugs are not a cure, since the virus remains hidden in the body, but they do prevent the onset of AIDS and thereby allow infected individuals to live productive lives. While a miracle for many, these drugs are not the solution to the HIV pandemic. For political, economic and social reasons, they are not readily available in the developing world and, even if they were, many countries lack the sophisticated health care systems to deliver and monitor treatment. The real solution is a vaccine that would protect individuals with a single shot and without a sophisticated health care system. Yet despite decades of work by the world's brightest minds, we still don't have an effective HIV vaccine.
Our planet is in the midst of a raging HIV pandemic. The World Health Organization reports that more than 34 million people are infected with HIV, 10 percent of whom are children under age 15. HIV is taking its greatest toll in the developing world, with Africa and Asia being primary hotspots. In addition to killing about two million people every year, the virus also reduces resistance to other infectious diseases. In fact, HIV is driving a major resurgence of tuberculosis and newly emerging drug-resistant forms that pose serious global threats.
HIV is transmitted through sexual contact, blood transfer (e.g., shared needle use) or pregnancy and breastfeeding. The virus then sets up shop in white blood cells — the body's immune system — and a race begins between the virus, which kills white blood cells, and the body, which desperately manufactures new white blood cell replacements. For a while, a balance is achieved, but eventually the virus prevails and the white blood cell count drops. This immune system exhaustion results in a declining capacity to fight all types of infections — a condition referred to as Acquired Immune Deficiency Syndrome, or AIDS. Eventually, the infected individual succumbs to diseases normally shrugged off. Even the common cold becomes lethal.
In recent years, drug treatments have led to the control of HIV in the developed world. Although the drugs are expensive and have significant side effects, they can suppress the virus. The drugs are not a cure, since the virus remains hidden in the body, but they do prevent the onset of AIDS and thereby allow infected individuals to live productive lives. While a miracle for many, these drugs are not the solution to the HIV pandemic. For political, economic and social reasons, they are not readily available in the developing world and, even if they were, many countries lack the sophisticated health care systems to deliver and monitor treatment. The real solution is a vaccine that would protect individuals with a single shot and without a sophisticated health care system. Yet despite decades of work by the world's brightest minds, we still don't have an effective HIV vaccine.
Major advances
Why has it been so difficult to develop a vaccine? The primary problem
is that the virus is constantly mutating and changing shape. As the
viruses “shape-shift,” they establish a swarm in which each individual
virus is different from one another. This causes the immune system to
misfire, a little like fending off a swarm of angry bees with a stick.
While the virus is tricky, researchers are finally beginning to identify
its Achilles' heel. The first major advance is the realization that
there are parts of the virus that can't change shape — that are somehow
constrained by the virus's biology. This includes the receptor that the
virus uses to attach to, and enter, white blood cells. Scientists have
known for some time that rare individuals are able to control HIV and
occasionally even eradicate it completely. It turns out that some of
these “elite controllers” have developed an immune response against
these constrained parts of the virus. In other words, the immune system
has focused its response on a weak spot, enabling it to tackle an entire
swarm of viruses despite the shape variation between individual
viruses. It now appears a vaccine might be developed that trains the
immune system to recognize constrained parts of the virus and turn
vaccinated individuals into “elite controllers.” The challenges remain
great, since it turns out to be very difficult to develop vaccines that
target these viral weak spots. The second major advance is the realization that when HIV is transmitted from individual to individual, the whole swarm is not transferred. Usually, only a single virus member is transmitted across a mucosal surface. As the immune system revs up to tackle the intruder, this single virus begins to replicate, and the daughter viruses start to mutate and change shape. By the time immune system cells arrive at the site of infection, a swarm has already developed capable of evading the immune system's firepower. Therefore, an effective vaccine would need to elicit immunity immediately at the infection site. If a vaccine could pre-establish immune response cells at the body's mucosal barriers, these sentinel cells would have a considerable advantage over the single transmitted virus; the immune system could strike before the viral swarm develops. Again, formidable challenges remain in training immune cells to reside in and continuously survey mucosal barriers.
Taken together, these two major advances in understanding how the immune system can beat HIV offer considerable hope for the field. It now seems highly likely that an effective HIV vaccine is in our future, and hopefully this nasty disease will be completely eradicated.
One final thought: In 1984, Keystone Symposia convened the first open, international scientific conference on AIDS, helping to catalyze the consensus among researchers that AIDS was caused by a retrovirus, HIV. Like that earlier paradigm shift for AIDS research, we dearly hope last week's Keystone Symposia HIV conference will mark another turning point.
David L. “Woody” Woodland, Ph.D. is the Chief Scientific Officer of Silverthorne-based Keystone Symposia on Molecular and Cellular Biology, a nonprofit dedicated to accelerating life science discovery by convening internationally renowned research conferences in Summit County and worldwide. Woody can be reached at (970) 262-1230 ext. 131 or woody@keystonesymposia.org.
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