Vaccinations with and against toxins face a conundrum: if they are too good, they can sicken their recipients.

Now, scientists have developed a nanoparticle to cage a certain class of toxins, allowing them to present those toxins to the immune system without first modifying them through chemical or heat treatment – a process that makes vaccines less toxic, but also less effective.

Mice vaccinated with a nanovaccine against the Staphylococcus aureus toxin hemolysin A were better protected from hemolysin than animals who received heat-treated hemolysin.

Liangfang Zhang, who is at the University of California at San Diego and the senior author of the paper reporting the results, called the particle a “hybrid biomimetic membrane.”

It consists of a core of PLGA, or poly (lactic-co-glycolic acid), covered in the membrane of a red blood cell. Nanoparticles for medical use, Zhang explained, “all face the same basic problem, and that is the immune response,” which makes short work of any nanoparticles it can find.

Many nanoparticles make themselves invisible to the immune system through a coating that gives them the properties of droplets. The biomimetic membrane takes the opposite approach, using camouflage that makes it look like a regular red blood cell to the immune system.

“Immune cells do attack red blood cells, but they don’t destroy them,” Zhang told BioWorld Today, because of “constant communication” between red blood cells and macrophages in the form of surface molecules. “We were inspired by this interaction.”

Zhang and his group first developed the nanoparticle with a therapeutic aim in mind. Earlier versions soaked up bacterial toxins in the bloodstream.

“When we did that project, we weren’t thinking of vaccines,” Zhang said. But the nanoparticles were so good at trapping the pore-forming toxins that it dawned on the scientists that they might be useful as a delivery vehicle of sorts.

In their newest experiments, which appeared in the Dec. 1 , 2013, issue of Nature Nanotechnology, Zhang and his team tested the notion that their nanoparticles could be used for exposing the immune system to those toxins as well.

The team created a nanoparticle whose membrane was studded with alpha-hemolysin, a virulence factor for S. aureus, and compared its effects with those of heat-treated S. aureus. They found that mice treated with the nanovaccine had higher levels of antibodies to hemolysin, and that those antibodies bound more tightly to their toxin target, than those vaccinated with heat-treated hemolysin.

The authors next vaccinated mice either in the bloodstream or subcutaneously, and then exposed them to hemolysin toxin some weeks later. For bloodstream infections, nanovaccine-treated mice had higher survival rates. For the complicated skin infections that can result from S. aureus, vaccination with the nanovaccine prevented skin necrosis.

Alpha-hemolysin is a member of a larger class of toxins, the pore-forming toxins. Such toxins are produced by bacteria including E. coli, H. pylori and other public (health) enemies. Animal venoms may also use pore-forming toxins.

Their name describes their game – pore-forming toxins insert themselves into cell membranes, causing them to spring leaks. Zhang and his team essentially turned that propensity against them, using their nanoparticle as a decoy to attract the toxins.

Pore-forming toxins are likely to be among the easier types of proteins to present to the immune system using this nanovaccine, since it’s easy to get them into the membrane. But Zhang thinks that the system could work for other proteins as well. “We just have to find a way to the antigen to the membrane,” he said.

The vaccine could be used both prophylactically and therapeutically, and because it combats a virulence factor rather than the bacterium itself, bugs are less likely to develop resistance than to classical antibiotics. And like the sponge Zhang and his colleagues tested in earlier work, such a vaccine could be used against several toxins at once, inserted into the same membrane.