Anthrax : Immunity, Vaccines and Diagnostics

by National Institute of Health

(Page 3 of 3)

Spore biology

B. anthracis spores are essentially dormant and must "wake up," or germinate, to become reproductive, disease-causing bacteria. Researchers are studying the germination process to learn more about the signals that cause spores to become active once inside an animal or person. Efforts are under way to develop models of spore germination in laboratory animals. Scientists hope those models will enable discoveries leading to drugs that block the germination process.

Host immunity

People who contract anthrax produce antibodies to protective antigen protein. Similar antibodies appear to block infection in animals. Recent studies also suggest that some animals can produce antibodies to components of B. anthracis spores. Those antibodies, when studied in a test tube, prevent spores from germinating and increase their uptake by the immune system's microbe-eating cells. These discoveries suggest that scientists might be able to develop a vaccine to fight both B. anthracis cells and spores.

Researchers also are studying how the immune system responds to B. anthracis infection. Part of the immune system response, known as adaptive immunity, consists of B and T cells that specifically recognize components of the anthrax bacterium. The other type of immune response-innate immunity-aims more generally to combat a wide range of microbial invaders and likely plays a key role in the body's front-line defenses. Scientists are conducting studies of how those two arms of the immune system act to counter infection, including how B. anthracis spore germination affects individual immune responses.

Natural history of anthrax

In 2002, NIAID physician researchers initiated a clinical protocol to study the natural history of anthrax. The goal is to look at the infectious disease process over time, from initial infection through the clinical course and beyond recovery. A small number of anthrax survivors from the 2001 attacks have enrolled. Because the medical literature on anthrax does not include any findings regarding long-term complications in survivors, information gained in this study will be valuable to patients and doctors.

Vaccines

Researchers have developed new, more effective anthrax vaccines intended for broad use. If approved by the Food and Drug Administration (FDA), it could be given to children, the elderly, and those with weakened immune systems more easily than the existing military anthrax vaccine. NIAID is currently funding two companies to develop, produce, and perform clinical trials of a next-generation vaccine based on a genetically modified recombinant protective antigen (rPA) protein. Antibodies produced by the immune system in response to rPA are thought to be the primary mode of protection against anthrax spores. NIAID is also funding research on the application of new vaccination technologies and novel compounds that can boost the immune response to a vaccine.

Diagnostics

Research is under way to develop improved techniques for spotting B. anthracis in the environment and diagnosing it in infected individuals. A key part of that research is the functional genomic analysis of the bacterium, which should lead to new genetic markers for sensitive and rapid identification. Genomic analysis will also reveal differences in individual B. anthracis strains that may affect how those bacteria cause disease or respond to treatment.

Therapies

Following the discoveries of how the protective antigen and lethal factor proteins interact with cells, researchers are screening thousands of small molecules in hopes of finding an anti-anthrax drug. In addition, NIAID is working with FDA, CDC, and the Department of Defense to accelerate testing of collections of compounds for their effectiveness against inhalational anthrax. Many of those compounds already have been approved by the FDA for other conditions and therefore could quickly be approved for use in treating anthrax, should they prove effective.

NIAID is also seeking new drugs that attack B. anthracis at many levels. These include agents that prevent the bacterium from attaching to cells, compounds that inhibit spore germination, and inhibitors that block the activity of key enzymes such as anthrax lethal factor. NIAID also will develop the capacity to synthesize promising anti-anthrax compounds in sufficient purity and quantity for preclinical testing.

About the Author

NIH is the nation's medical research agency - making important medical discoveries that improve health and save lives. The National Institutes of Health (NIH), a part of the U.S. Department of Health and Human Services, is the primary Federal agency for conducting and supporting medical research.