New nanoparticle vaccine is more effective but less expensive

Described in an article appearing online September 16 in the journal Nature Biotechnology, the vaccine delivery platform is a deceptively simple combination of nanotechnology and chemistry that represents a huge advantage over current vaccine methods. 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 the developing world.

A vaccination is an injection of a non-virulent form of a pathogen or molecule from a pathogen (known as an antigen), to which the immune system responds, destroying and then developing a “memory” for the pathogen. Later, when a virulent form of the pathogen comes along, this memory kicks in and the intruder is quickly eradicated. Most vaccines protect against viruses or bacteria, but vaccine techniques are also being explored as a way to kill cancer cells.

Thanks to recent advances, an immune response can be triggered with just a single protein from a virus or bacterium. 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.”

Cost and logistics are important factors, especially for use in developing countries. Unlike other nanoparticle vaccine technologies that degrade in water and thus require expensive drying and handling procedures, the EPFL team’s nanoparticles won’t degrade until they are in the body. They are in liquid form and don’t require refrigeration, so preparation and handling costs are reduced, and they are easy to transport.

The group is collaborating with the Swiss Tropical Institute in Basel to determine the strength and duration of the immune response in the context of a nanoparticle malaria vaccine. Toxicity studies are also in the works. Swartz says that the team is also planning to use this technique to target cancer cells.

“If, as we hope, this vaccine technique can confer sustained immunity with a single injection for around a dollar a dose, without toxic side effects, it could have a real impact on public health, in the developing world as well as right here at home,” says Swartz. “More study is required to achieve these goals,” she adds, “but we have every reason to believe this technique could be in use within five years.”

Source: Ecole Polytechnique Fédérale de Lausanne

Plants make vaccine for treating type of cancer
Plants could act as safe, speedy factories for growing antibodies for personalized treatments against a common form of cancer, according to new findings from the Stanford University School of Medicine. The findings came in the first human tests of an injectable vaccine grown in genetically engineered plants.
Viral recombination another way HIV fools the immune system
When individuals infected with HIV become infected with a second strain of the virus, the two viral strains can exchange genetic information, creating a third, recombinant strain of the virus. It is known that the presence of multiple viral strains, called superinfection, frequently leads to a loss of immune control of viral levels. Now a study from the Partners AIDS Research Center at Massachusetts General Hospital (PARC/MGH) shows that how and where viral strains swap DNA may be determined by the immune response against the original infecting strain. Their report will appear in the Journal of Experimental Medicine and has been released online.
Researchers use salmonella to administer vaccines
(PhysOrg.com) -- Researchers at the Biodesign Institute at Arizona State University have made a major step forward in their work to develop a biologically engineered organism that can effectively deliver an antigen in the body. The researchers report that they have been able to use live salmonella bacterium as the containment/delivery method for an antigen.
HIV conquers immune system faster than previously realized
New research into the earliest events occurring immediately upon infection with HIV-I shows that the virus deals a stunning blow to the immune system earlier than was previously understood. According to scientists at Duke University Medical Center, this suggests the window of opportunity for successful intervention may be only a matter of days – not weeks – after transmission, as researchers had previously believed.
A Viral Cloaking Device: Biologists show how Human Cytomegalovirus hides from the immune system
(PhysOrg.com) -- Viruses achieve their definition of success when they can thrive without killing their host. Now, biologists Pamela Bjorkman and Zhiru Yang of the California Institute of Technology have uncovered how one such virus, prevalent in humans, evolved over time to hide from the immune system.
Novel computational model describes the speed at which HIV escapes the immune response
Researchers from Utrecht University, The Netherlands, have developed a model that illustrates how HIV evades the immune system. The study, published July 18th in the open-access journal PLoS Computational Biology, incorporates detailed interactions between a mutating virus and the immune system.
Vaccine for koala chlamydia close
Professors Peter Timms and Ken Beagley from Queensland University of Technology's Institute of Health and Biomedical Innovation (IHBI) said the vaccinated koalas, which are at Brisbane's Lone Pine Koala Sanctuary, were mounting a good response to the vaccine.
Booster vaccination may help with possible future avian influenza pandemic
New evidence suggests that a booster vaccination against H5N1 avian influenza given years after initial vaccination with a different strain may prove useful in controlling a potential future pandemic. The study is published in the August 1 issue of The Journal of Infectious Diseases, now available online.

New nanoparticle vaccine is more effective but less expensive

Related stories:

News discussion: