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Dec 2, 2013

Nanosponge Vaccine Breaks through Safety/Efficacy Tradeoff

  • For all their promise, many toxoid vaccines pose a vexing tradeoff—the safer they are, the less effective the immune response they promote. Alternatively, the least distorted form of a bacterial toxin—unprocessed either chemically or thermally—would be too dangerous to use as a toxoid vaccine, particularly in the case of pore-forming toxins, such as those produced by MRSA (methicillin-resistant Staphylococcus aureus). Such a toxoid vaccine would run riot, punching holes in cells, causing lethal leaks.

    But what if the most dangerous toxins were left unaltered chemically, and were instead constrained, made part of a toxoid vaccine package? That’s the vaccine development approach being explored by researchers at the University of California, San Diego. At first, these researchers had little thought of constructing vaccines. They were busy constructing nanosponges that showed promise as drug delivery vehicles. These nanosponges, the researchers noticed, proved effective at soaking up toxins. Then, they were struck by the potential use of a particle full of toxins—a toxoid vaccine.

    The researcher’s nanosponges are biocompatible particles made of a polymer core wrapped in a red-blood-cell membrane. In one set of experiments, each nanosponge’s red-blood-cell membrane was used to seize and detain the Staphylococcus aureus (staph) toxin alpha-hemolysin without compromising the toxin’s structural integrity. The result: a toxin-studded nanosponge vaccine.

    In experiments with mice, the nanosponge vaccine was safe and more effective than toxoid vaccines made from heat-treated staph toxin. After one injection, just 10% of staph-infected mice treated with the heated version survived, compared to 50% for those who received the nanosponge vaccine. With two more booster shots, survival rates with the nanosponge vaccine were up to 100%, compared to 90% with the heat-treated toxin.

    These results appear in a paper published December 1 in Nature Nanotechnology. In this paper, entitled “Nanoparticle-detained toxins for safe and effective vaccination,” the authors write, “We find that the non-disruptive detoxification approach benefited the immunogenicity and efficacy of toxoid vaccines. We anticipate that this study will open new possibilities in the preparation of antitoxin vaccines against the many virulence factors that threaten public health.”

    According to the paper’s senior author, Liangfang Zhang, Ph.D., a nanoengineering professor at UC San Diego Jacobs School of Engineering, “The nanosponge vaccine was also able to completely prevent the toxin’s damages in the skin, where MRSA infections frequently take place.”

    The particles “work so beautifully”" Dr. Zhang added, that it might be possible to detain several toxins at once on them, creating “one vaccine against many types of pore-forming toxins,” from staph to snake venom.

    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 nanopore approach is especially interesting because there are no vaccines approved to protect humans against the toxins associated with staph infections, including those caused by MRSA strains. In addition, as the problem of antibiotic resistance worsens, toxoid vaccines offer a promising approach to fight infections without reliance on antibiotics.



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