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Vol. LVIII, No. 1
January 13, 2006
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Vaccine Research Progressing

Vaccines aim to prevent diseases by stopping microbes from getting a toehold in your body in the first place. Traditional vaccines use a variety of approaches, including using weakened or killed microorganisms or portions of them to "teach" the immune system to attack if it ever encounters the real thing. Unfortunately, some microbes can elude these methods. HIV, for example, infects the very immune cells that arrive to fight it, making effective vaccine design a particular challenge. But new strategies for developing vaccines are in the works and 2005 saw significant advances in the field.

DNA vaccines are showing great promise, and are already being used to help protect some animals. While none have yet been licensed for human use, DNA vaccines against HIV, Ebola, West Nile virus and SARS are currently being tested at NIAID's Dale and Betty Bumpers Vaccine Research Center (VRC). DNA vaccines can be manufactured more quickly than traditional vaccines. They also result in antigens being presented by the body's own cells, so they're more likely than some traditional vaccines to stimulate both antibody and cell-based attacks from the immune system. One trial that opened earlier this year, for example, is testing an experimental vaccine against West Nile virus. The vaccine, which consists of a DNA plasmid with genes coding for two key viral surface proteins, is injected into muscle, where muscle cells can read the DNA, produce the two proteins and display them on their surfaces.

A safe, effective HIV vaccine is perhaps the most prominent vaccine research goal and several HIV vaccines are now in the pipeline. One such vaccine, developed by scientists at the VRC, moved into its second phase of clinical testing in October. This vaccine contains synthetic genes representing HIV subtypes found in Europe, North America, Africa and Asia that comprise about 85 percent of HIV infections worldwide. For greater potency, the researchers are using a one-two punch strategy, starting out by vaccinating with naked gene fragments, then following up with a booster shot using weakened adenovirus to deliver selected genes.

An innovative vaccine strategy funded by NHLBI aims to bypass the need for helper T cells, normally a key component in the immune response. Researchers at Children's Hospital of Pittsburgh focused on a molecule on the surface of helper T cells called CD40L that signals other cells like antibody-producing B cells to mount their attack. The team combined CD40L with a key antigen from pneumocystis pneumonia and showed that the vaccine was able to protect mice lacking helper T cells from pneumocystis. The ability to develop vaccines for humans that could bypass helper T cells would be a major breakthrough for people with compromised immune systems like those with HIV or organ transplants.

Another interesting area of vaccine development comes from the cancer research arena. The immune system generally doesn't recognize tumors to mount attacks against them. But with a little help, unique or unusually abundant molecules on the surface of cancer cells can prompt the immune system to act. New vaccines are now showing promise for stimulating the immune system to attack cancer cells. According to NCI, several clinical trials are under way to test vaccines for a wide variety of cancers. For more information, visit www.cancer.gov/cancertopics/factsheet/cancervaccine.

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