Vaccine To Fight Naturally Occurring Plague And Bioterrorism Too

 Gopalan T on January 26, 2011
US scientists could be closer to developing a vaccine that fights both the naturally plague and the bacteria that is sought to be used by terrorists for mass slaughter.
“Governments remain concerned that bioweapons of aerosolized Yersinia pestis, the bacteria that causes plague, could kill thousands,” said Stephen Smiley, a leading plague researcher and Trudeau Institute faculty member.
The anthrax scare that followed the terror attacks of September 11, 2001, made the threat of bioterrorism real and led to a surge in federal funding into research aimed at heading off such threats.
According to Dr. Smiley, there is no licensed plague vaccine in the United States. Together with postdoctoral associate Jr-Shiuan Lin, he is working to develop a vaccine that will protect members of the armed services and public from a “plague bomb.”
Yersinia pestis is arguably the most deadly bacteria known to man. Plague infections of the lung, known as pneumonic plague, are extremely lethal. The bacteria, which grow both inside and outside the cells of the lung, usually lead to death within a week of infection.
Most of the plague vaccine candidates that have been studied aim to stimulate B cells to produce plague-fighting antibodies. However, animal studies suggest that antibodies may not be enough to protect humans from pneumonic plague. The Smiley laboratory has shown that T cells can also fight plague. The lab previously demonstrated that a single immunization with an experimental vaccine stimulates the production of T cells that provide partial protection against pneumonic plague.

www.medindia.net/news/Vaccine-To-Fight-Naturally-Occurring-Plague-And-Bioterrorism-Too-79934-1.htm#ixzz1CWq4Anby

BIOTERRORISM: New Discovery Could Lead to Vaccines for Plague and Bacterial Pneumonia

There is an ongoing battle in the "war on terror" that remains mostly unseen to the public -- a race between scientists working to develop a vaccine to protect against plague and the terrorists who seek to use plague as a weapon.
"Governments remain concerned that bioweapons of aerosolized Yersinia pestis, the bacteria that causes plague, could kill thousands," says Stephen Smiley, a leading plague researcher and Trudeau Institute faculty member.
The anthrax scare that followed the terror attacks of September 11, 2001, made the threat of bioterrorism real and led to a surge in federal funding into research aimed at heading off such threats.
According to Smiley, there is no licensed plague vaccine in the United States. Together with postdoctoral associate Jr-Shiuan Lin, he is working to develop a vaccine that will protect members of the armed services and public from a "plague bomb."
Yersinia pestis is arguably the most deadly bacteria known to man. Plague infections of the lung, known as pneumonic plague, are extremely lethal. The bacteria, which grow both inside and outside the cells of the lung, usually lead to death within a week of infection.
Most of the plague vaccine candidates that have been studied aim to stimulate B cells to produce plague-fighting antibodies. However, animal studies suggest that antibodies may not be enough to protect humans from pneumonic plague. The Smiley laboratory has shown that T cells can also fight plague. The lab previously demonstrated that a single immunization with an experimental vaccine stimulates the production of T cells that provide partial protection against pneumonic plague.
New data, reported in the current issue of the Journal of Immunology, show that a second immunization, or booster, improves the protection provided by T cells. "It is particularly exciting that the boost seems to improve protection by increasing a newly described type of T cell, which we call a Th1-17 cell," says Smiley. These cells have characteristics of both Th1 cells, which defend against intracellular bacteria, and Th17 cells, which specialize at killing extracellular threats.
This research is focused primarily on thwarting the use of plague as a bioweapon. However, small, natural outbreaks of plague continue to this day. A plague vaccine will protect against both naturally occurring outbreaks and those that have been manufactured.
Additionally, Smiley believes these Th1-17 cells may be important in fighting other kinds of pneumonia: "Bacterial pneumonia is one of the most common causes of death in hospitals and, like plague, many of these pneumonias are caused by bacteria that grow both inside and outside the cells of our bodies."
Smiley’s studies are funded by the Trudeau Institute and grants from the National Institutes of Health. The Trudeau Institute is an independent, not-for-profit, biomedical research organization, whose scientific mission is to make breakthrough discoveries leading to improved human health. Trudeau researchers are identifying the basic mechanisms used by the immune system to combat viruses like influenza, mycobacteria, such as tuberculosis, parasites and cancer, so that better vaccines and therapies can be developed for fighting deadly disease.
The research is supported by government grants and philanthropic contributions
http://www.infectioncontroltoday.com/news/2011/01/new-discovery-could-lead-to-vaccines-for-plague-and-bacterial-pneumonias.aspx

TUBERCULOSIS: Molecular profiling

Thanks to molecular profiling, scientists now have a better idea about how a mass killer selects its victims. And the new analysis suggests that the killer, TB, may use a different murder weapon than researchers previously believed.
Mycobacterium tuberculosis infects one-third of people worldwide. But only about 10 percent of people infected will actually get sick with a debilitating lung disease. Until now, scientists had no way to predict who would become ill.
Now, an international consortium of researchers has compiled profiles of genetic activity in the blood of people with dormant TB infections, people with active infections, and healthy people. Those profiles show how the immune system deals with tuberculosis and point to some surprising culprits responsible for awakening a slumbering infection. Such profiles may help predict who will succumb to TB, the researchers report in the Aug. 19 Nature.
“This is literally the way to tell who is going to get sick,” says Clifton Barry, chief of the tuberculosis research section at the U.S. National Institute of Allergy and Infectious Diseases in Bethesda, Md. This study could revolutionize TB diagnosis in the same way that breast cancer treatments were forever changed by the discovery that some tumor cells make molecules that respond to estrogen, and that those molecules can serve as targets for chemotherapy, Barry says.
In the new study, researchers drew blood from TB patients and from healthy people in London and analyzed gene activity in the blood cells. People who had active infections had 393 genes with activity different from that seen in healthy people. The team could classify people into groups—no infection, latent infection or active illness—just by looking at the gene activity profiles in their blood. The findings were replicated in a separate group of patients from Cape Town, South Africa. The TB signature disappeared as people were treated with antibiotics.
About 10 to 25 percent of people with latent infections had signatures similar to those of people with active infections, indicating that people with the active profile may go on to develop the disease even if their infection is currently dormant, says study coauthor Matthew Berry of the MRC National Institute for Medical Research in London. The researchers are planning to follow people with latent infections to see if those with the signature really are the same ones who develop active infections later. If the results hold up, the blood profiles could be the first means of predicting who is likely to get sick from TB.
That could spare people from developing a lung-damaging infection, but may also mean that people who aren’t likely to get sick won’t need to take anti-TB drugs that can damage the liver.
Blood cells called neutrophils also appeared in the new study to be important for spreading the disease. Previously, researchers didn’t think that short-lived neutrophils could play any role in such a long-term infection as tuberculosis. The dogma in the field was that the bacterium infected only immune cells called macrophages, says study leader Anne O’Garra, also of the MRC National Institute for Medical Research. The new study indicates that genes turned on by a protein known as type 1 interferon become active in the neutrophils of people with full-blown TB. Interferon helps to fight off viral infections but may actually make bacterial infections such as TB even worse, O’Garra says.
These findings fit well with recent data from mouse studies implicating both neutrophils and interferon in serious disease caused by tuberculosis, says Andrea Cooper, an infectious disease immunologist at the Trudeau Institute in Saranac Lake, N.Y.
“We’re at a watershed here in changing what we think the disease is about,” she says.
TB’s molecular signature was distinct from the profiles of blood taken from people with autoimmune diseases, such as lupus, and from those with other infectious diseases like Streptococcus or Staphylococcus infections, the researchers found. The discovery was unexpected, as most researchers thought that different types of bacteria might change the activity of specific genes at the site of the infection but that those differences would not show up in the blood, Cooper says. The variety of signatures indicates that the immune system has developed multiple ways of dealing with infectious organisms.
“It highlights the beauty of the immune response and its finesse in dealing with different pathogens,” Cooper says.
http://www.usnews.com/science/articles/2010/08/19/gene-profiles-may-predict-tb-prognosis.html