'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