A group of investigators at the Ecole Polytechnique Fédérale de Lausanne animal-tested a nanoparticle-based vaccine (nanoparticles conjugated to the model antigen ovalbumin), and found a promising immunologic response, both humoral and cellular:
Bioengineering researchers from the EPFL in Lausanne, Switzerland, have developed and patented a nanoparticle that can deliver vaccines more effectively, with fewer side effects, and at a fraction of the cost of current vaccine technologies…
This technology may make it possible to vaccinate against diseases like hepatitis and malaria with a single injection. And at an estimated cost of only a dollar a dose, this technology represents a real breakthrough for vaccine efforts in underdeveloped countries…
Recent research has also shown that the best way to get sustained immunity is to deliver an antigen directly to specialized immune cells known as dendritic cells (DCs).
This technique is not yet used clinically because there are two difficulties to overcome in targeting the DCs: first, there are not very many of these cells in the skin or muscle, where injections are usually made, so obtaining an adequate immune response with a single injection is difficult; and second, activating the DCs requires co-delivering a “danger signal” of some sort, otherwise the immune system will just ignore it. Current approaches mimic bacterial molecules already known to the immune system, but this can cause side effects or even be toxic.
EPFL professors Jeff Hubbell and Melody Swartz and PhD student Sai Reddy have engineered nanoparticles that completely overcome these limitations. At a mere 25 nanometers, these particles are so tiny that once injected, they flow through the skin’s extracellular matrix, making a beeline to the lymph nodes. Within minutes, they’ve reached a concentration of DCs thousands of times greater than in the skin. The immune response can then be extremely strong and effective.
In addition, the EPFL team has also engineered a special chemical coating for the nanoparticles that mimics the surface chemistry of a bacterial cell wall. The DCs don’t recognize this as a specific invader, but do know that it’s something foreign, and so a low-level, generic immune reaction known as “complement” is triggered. This results in a particularly potent immune response without the risk of unpleasant or toxic side effects.
“People have been exploring nanoparticles for a while,” says Hubbell. “Our ideas — to activate complement as a danger signal, and to exploit the slow interstitial flow towards the lymph nodes – are completely new. But it meant that our particles had to be much smaller than anything currently being developed. No other labs have managed to engineer so many levels of functionality into nanoparticles that are smaller than biologically occurring particles,” he adds. “The beauty of it is that once we have developed the recipe, any lab can make them.”
The paper @ Nature Biotechnology: Exploiting lymphatic transport and complement activation in nanoparticle vaccines …
Press release: EPFL develops new nanoparticle vaccine …
Image: Dendritic cell with podosomes.
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