UCSD scientists have created a vaccine for the deadly MRSA infection, using ‘nanosponge’ technology they previously used to soak up MRSA toxins and other poisons and venoms. The vaccine is effective in mice, they showed in a study; and their goal is to get it into human clinical trials.
The nanosponges are built on a polymer core wrapped with membranes from red blood cells that seize the toxins. They were first loaded with the MRSA toxins and injected into mice. The mouse immune system recognized the toxins and developed antibodies. The vaccinated mice were then able to survive an otherwise lethal dose of the toxins.
The study was published Sunday in Nature Nanotechnology. Liangfang Zhang, a nanoengineering professor at UC San Diego Jacobs School of Engineering, was senior author on the paper.
MRSA, or methicillin-resistant Staphylococcus aureus, has become one of the “superbugs” plaguing hospitals, and even some locations outside hospitals, because it has evolved potent resistance to antibiotics. The prospect of antibiotics becoming useless has become a nightmare scenario for modern health care. Without effective antibiotics, infections that were once easily treatable could once again become fatal, as they often were in the days before antibiotics were discovered.
But MRSA’s lethality is mainly indirect, through a toxin called alpha-haemolysin. The toxin kills cells by punching holes in them. If that toxin were to be neutralized, the bacterium would be much less dangerous.
“With our toxoid vaccine, we don’t have to worry about antibiotic resistance. We directly target the alpha-haemolysin toxin,” Zhang said in a UCSD news release.
The nanosponge vaccine solves a tricky problem in vaccinating against MRSA, Zhang said. The toxin from MRSA is too dangerous to be given unaltered. So it is heated or chemically treated to weaken it for vaccine development.. But the altered toxin is less effective in provoking an effective antibody response than the unaltered toxin.
Immune cells called dendritic cells seek out the toxin-laden vaccine and process it, leading to antibody production by other immune cells. Free toxin kills dendritic cells, but trapping it in the vaccine’s membrane reduces its dangerous without altering the toxin itself.
“The researchers found that their nanosponge vaccine was safe and more effective than toxoid vaccines made from heat-treated staph toxin,” the news release stated. “After one injection, just 10 percent of staph-infected mice treated with the heated version survived, compared to 50 percent for those who received the nanosponge vaccine. With two more booster shots, survival rates with the nanosponge vaccine were up to 100 percent, compared to 90 percent with the heat-treated toxin.”
Previously, “there was no way you could deliver a native toxin to the immune cells without damaging the cells,” Zhang said in the release. “But this technology allows us to do this.”
In April, Zhang and colleagues published a paper in Nature Nanotechnology showing how the nanosponges could increase survival of mice injected with toxins from MRSA and other sources.
The nanosponges soaked up the toxins, which adhered to the red blood cell membranes. By reducing the amount of freely circulating toxins, the nanosponges increased survival.
Zhang and colleagues originally developed the nanosponges as a delivery vehicle for cancer drugs. The goal was to keep the drugs active in the body for longer periods of time, by guarding them against detection and destruction by the immune system.