deadly strain. infections by MRSA bacteria (purple) highlight the need for S. aureus vaccine.
NIH
staph infections represent one of the most serious microbial threats to people. Yet efforts to prevent with vaccines have always failed, even though the bacteria responsible is becoming increasingly resistant to antibiotics. Now, an experimental vaccine with new ingredients was very protective in rabbits against staphylococcal pneumonia, one of the most dangerous results from bacterial infection. The inventor hopes to take human studies soon.
Staphylococcus aureus is thought to colonize the nose of about one third of the human being at some point, but it also causes about half a million hospitalizations and 20,000 deaths each year in the United States. The strains of the bacteria that are resistant to most antibiotics, particularly MRSA doubled varieties (methicillin-resistant S. Aureus ), have become a major threat, emphasizing the need for a vaccine against the microbe.
However, a series of vaccines has undergone dramatic failures in recent years. A candidate of Nabi Biopharmaceuticals of Rockville, Maryland, flopped in two trials in dialysis patients in the United States, and a Merck vaccine was abandoned in 2012 after millions of dollars were spent testing.
microbiologist Patrick Schlievert of the University of Iowa in Iowa City believes that pharmaceutical companies were under way on a vaccine against the wrong direction. Previous staphylococcal vaccines have attempted to provide protection including protein or carbohydrates in the natural capsule that surrounds the cell wall of the bacterium staphylococcus and allows it to evade the immune system. This approach was successful for vaccines against other bacteria as Haemophilus influenzae type B and Streptococcus pneumoniae , but did not work with S. aureus. Other vaccines that failed included simple proteins from the cell wall of S. aureus bacteria.
In an article published online this month The Journal of Infectious Diseases, Schlievert and colleagues took a new approach. The strategy involves an entirely different class of substances extracted from S. aureus bacteria. These included so-called superantigens and cytolysins proteins that are produced by S. aureus internal structures and play a major role in diseases caused by bacteria. Researchers vaccinated 88 rabbits, divided into several groups with different combinations of these substances. All but two of the animals survived when S. aureus bodies were sprayed into their lungs. 88 unvaccinated rabbits exposed to the same bacteria, only one survived.
In another experiment, the researchers found evidence that typical vaccines can actually make those immunized more vulnerable to a staph infection. They vaccinated five rabbits neutralized with proteins from the cell surface S. aureus -the type of substances used in most previous and current candidate vaccines. All five of these animals died within 6 hours of exposure to a common MRSA strain; however, five non-vaccinated animals survived at least 4 days after exposure.
results against-intuitive The studies are consistent with previous research by Schlievert indicating that the cell surface antigens, which are frequently used to create bacterial vaccines are poor choice for prophylactic to S. aureus because of particular way the body to cause disease, he said.
"One of the ways Staphylococcus works is to create aggregations of bacteria which block blood vessels and airways," said Schlievert. Therefore, vaccines that stimulate the creation of antibodies against antigens of cell surface can be more dangerous than no vaccine at all, he said, because in connection with these antigens, they created molecular complexes that intensify the phenomenon of agglutination.
Schlievert also believes that its results are more relevant to humans than other animal studies with staphylococcal vaccines. While other researchers tested S. aureus vaccines in mice and non-human primates, supports the immune system of the rabbit is more similar to that of humans, at least in terms of how it responds to this bacteria. Staph researchers say the new study Schlievert is provocative, but not entirely convincing. "It shows that superantigens are more protective than the antigen-bunnies area undergoing experimental infection," said Robert Daum, a pediatrician and microbiologist at the University of Chicago in Illinois. It remains to be seen whether the same is true in humans, he says. "Many people have used surface antigens [in vaccines] for a long time. it was not a great success, but there is little evidence to suggest that vaccines are worse. "
Daum considers the suggestion that rabbits were better than mice as experimental animals to be interesting. It is true that mice are not particularly good models in S. aureus , he said, but then, rodents are inexpensive and well studied. "If it is true that rabbits are a better model, it Roil the field, because they are much more expensive and difficult to work with. I think rabbits have not yet been studied enough to conclude that they are better . "most of the data come from group Schlievert this.
Daum argued that failures in previous vaccines have shown that defeat S. aureus requires more basic science before new vaccine antigens are debited. Too little is understood about the human immune response to S. aureus , which can cause fatal infections, but often live in and on us without causing disease at all. "We do not want to eliminate all staphylococci. We want to eliminate the bad ones that cause the disease. So we need to understand immunology, and we are not yet there," said Daum.
Schlievert said that unpublished data from his group show that its also superantigen-based vaccines prevent skin infections in rabbits. It then intends to ask the Food and Drug Administration to allow it to conduct safety studies of the vaccine base man.
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