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January 25, 2011

Progress to vaccines against the Plague, bacterial pneumonias, Malaria and TB

TB causes symptoms such as coughing, chest pains and weight loss

1. BBC News reports that a new vaccine that can fight tuberculosis (TB) before and after infection has been developed by Danish scientists. There are nine million new TB cases globally each year and increasing levels of drug resistance new diagnostics, drugs and especially effective vaccines are desperately needed. The new treatment combines proteins that trigger an immune response to both the active and latent forms of Mycobacterium. It might be possible to give a booster jab post-exposure to older children or even young adults which would protect them well into adulthood.

TB is a huge global problem, particularly in developing countries, where access to antibiotics to treat the disease is limited. The latest vaccine, so far tested in animals, is featured in the journal Nature Medicine. TB is a disease of the lungs, causing symptoms such as coughing, chest pains and weight loss. Untreated, it can be deadly.

However, only in a small number of cases - fewer than 5% - do the symptoms develop immediately after infection. In more than 90% of cases, once Mycobacterium tuberculosis, the bacterium which causes the disease, has invaded the body it changes its chemical signature, and lives in a dormant - or "latent" - state.

Current vaccines, such as the BCG vaccine, work only if given before exposure to the bacterium.




2. A new discovery with T Cells could lead to vaccines for the plague and bacterial pneumonias T cells can also fight plague and single immunization stimulates partial protection. Now they have found that a second immunization, or booster, improves the protection provided by T cells.

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."



3. Using the latest super resolution microscopy, researchers have caught the malaria parasite invading red blood cells for the first time. The researchers, led by the WEHI's Dr Jake Baum, Mr David Riglar and Dr Dave Richard, believe this breakthrough could lead to new malaria treatments as well as new methods for evaluating the effectiveness of experimental anti-malaria drugs.



4. Researchers newly report evidence that vaccination against cholera can be beneficial even after an outbreak has begun. The recent outbreaks of cholera in Haiti, Pakistan, and Zimbabwe suggest that current global action plans against cholera are failing. "Although everyone agrees that the ultimate prevention and control of cholera will require provision of clean water and adequate sanitation to the world's population, the simple fact is that this will not be a reality for decades for the world's most impoverished, as well as for those affected by civil unrest and natural disasters," says Dr. Edward T. Ryan.

Reyburn and colleagues model the effect of cholera vaccine once an outbreak has occurred using data from a number of recent outbreaks. The researchers modeled 50% and 75% vaccine coverage, with completion of vaccination ranging from "rapid" (10 weeks after an outbreak was first reported), to a "maximum" of completion of vaccination 33 weeks after an outbreak is first reported. They found that even delayed responses could have benefit, and their model neither included herd effect modifiers, nor the effect that vaccination could have on subsequent disease burden after the initial outbreak has waned into an endemic situation.

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