Nanotechnology Made Clear

'Nanosponge vaccine' fights MRSA toxins

The nanosponges at the foundation of the experimental "toxoid vaccine" platform are bio-compatible particles made of a polymer core wrapped in a red-blood-cell membrane. Each nanosponge's red-blood-cell membrane seizes and detains the Staphylococcus aureus (staph) toxin alpha-haemolysin without compromising the toxin's structural integrity through heating or chemical processing. These toxin-studded nanosponges served as vaccines capable of triggering neutralizing antibodies and fighting off otherwise lethal doses of the toxin in mice.

Toxoid vaccines protect against a toxin or set of toxins, rather than the organism that produces the toxin(s). As the problem of antibiotic resistance worsens, toxoid vaccines offer a promising approach to fight infections without reliance on antibiotics.

"With our toxoid vaccine, we don't have to worry about antibiotic resistance. We directly target the alpha-haemolysin toxin," said Liangfang Zhang, a nanoengineering professor at UC San Diego Jacobs School of Engineering and the senior author on the paper. Targeting the alpha-haemolysin toxin directly has another perk. "These toxins create a toxic environment that serves as a defense mechanism which makes it harder for the immune system to fight Staph bacteria," explained Zhang.

Beyond MRSA and other staph infections, the nanosponge vaccine approach could be used to create vaccines that protect against a wide range of toxins, including those produced by E. coli and H. pylori.

This work from Zhang's Nanomaterials and Nanomedicine Laboratory at the UC San Diego included nanoengineering post-doctoral researcher Che-Ming "Jack" Hu, nanoengineering graduate student Ronnie Fang, and bioengineering graduate student Brian Luk.

The researchers found that their nanosponge vaccine was safe and more effective than toxoid vaccines made from heat-treated staph toxin. 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.


"The nanosponge vaccine was also able to completely prevent the toxin's damages in the skin, where MRSA infections frequently take place," said Zhang, who is also affiliated with the Moores Cancer Center at UC San Diego.

Fighting Pore-Forming Toxins

This work is a twist on a project the UC San Diego nanoengineers presented earlier this year: a nanosponge that can sop up a variety of pore-forming toxins—from bacterial proteins to snake venom—in the body.

Pore-forming toxins work by punching holes in a cell's membrane and letting the cell essentially leak to death. But when toxins attack the red blood cell membrane draped over the nanoparticle, "nothing will happen. It just locks the toxin there," Zhang explained.

The nanosponges at the foundation of the experimental "toxoid vaccine" platform are bio-compatible particles made of a polymer core wrapped in a red-blood-cell membrane. Each nanosponge's red-blood-cell membrane seizes and detains the Staphylococcus aureus (staph) toxin alpha-haemolysin without compromising the toxin's structural integrity through heating or chemical processing. These toxin-studded nanosponges served as vaccines capable of triggering neutralizing antibodies and fighting off otherwise lethal doses of the toxin in mice.

Toxoid vaccines protect against a toxin or set of toxins, rather than the organism that produces the toxin(s). As the problem of antibiotic resistance worsens, toxoid vaccines offer a promising approach to fight infections without reliance on antibiotics.

"With our toxoid vaccine, we don't have to worry about antibiotic resistance. We directly target the alpha-haemolysin toxin," said Liangfang Zhang, a nanoengineering professor at UC San Diego Jacobs School of Engineering and the senior author on the paper. Targeting the alpha-haemolysin toxin directly has another perk. "These toxins create a toxic environment that serves as a defense mechanism which makes it harder for the immune system to fight Staph bacteria," explained Zhang.

Beyond MRSA and other staph infections, the nanosponge vaccine approach could be used to create vaccines that protect against a wide range of toxins, including those produced by E. coli and H. pylori.

This work from Zhang's Nanomaterials and Nanomedicine Laboratory at the UC San Diego included nanoengineering post-doctoral researcher Che-Ming "Jack" Hu, nanoengineering graduate student Ronnie Fang, and bioengineering graduate student Brian Luk.

The researchers found that their nanosponge vaccine was safe and more effective than toxoid vaccines made from heat-treated staph toxin. 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.

"The nanosponge vaccine was also able to completely prevent the toxin's damages in the skin, where MRSA infections frequently take place," said Zhang, who is also affiliated with the Moores Cancer Center at UC San Diego.

Fighting Pore-Forming Toxins

This work is a twist on a project the UC San Diego nanoengineers presented earlier this year: a nanosponge that can sop up a variety of pore-forming toxins—from bacterial proteins to snake venom—in the body.

Pore-forming toxins work by punching holes in a cell's membrane and letting the cell essentially leak to death. But when toxins attack the red blood cell membrane draped over the nanoparticle, "nothing will happen. It just locks the toxin there," Zhang explained.

UC San Diego, December 2, 2013

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