Thursday, January 9, 2014

On-demand vaccines possible with engineered nanoparticles

January 9, 2014
This image shows a collection of vaccinating nanoparticles from 40 to 50 nanometers in size. The inset graphic is a representation of how the engineered proteins decorate a nanoparticle’s surface. (Credit: University of Washington)
University of Washington engineers hope a new type of vaccine they have shown to work in mice will one day make it cheaper and easy to manufacture on-demand vaccines for humans. Immunizations could be administered within minutes where and when a disease is breaking out.
Vaccines usually are made en masse in centralized locations far removed from where they will be used. They are expensive to ship and keep refrigerated and they tend to have short shelf lives.
Just-in-time manufacturing
The new technology makes it possible to produce a vaccine on the spot. “For instance, a field doctor could see the beginnings of an epidemic, make vaccine doses right away, and blanket vaccinate the entire population in the affected area to prevent the spread of an epidemic,” said François Baneyx, a UW professor of chemical engineering and lead author of a recent paper published online in the journal Nanomedicine.
In typical vaccines, weakened pathogens or proteins found on the surface of microbes and viruses are injected into the body along with compounds called adjuvants to prepare a person’s immune system to fight a particular disease. But standard formulations don’t always work, and the field is seeking ways to manufacture vaccines quicker, cheaper and tailored to specific infectious agents, Baneyx said.
Vaccinating nanoparticles
The UW team injected mice with nanoparticles synthesized using an engineered protein that both mimics the effect of an infection and binds to calcium phosphate, the inorganic compound found in teeth and bones. After eight months, mice that contracted the disease made threefold the number of protective “killer” T-cells — a sign of a long-lasting immune response — compared with mice that had received the protein but no calcium phosphate nanoparticles.
The nanoparticles appear to work because their 40–50 nm size allows for ferrying the protein to the lymph nodes, where they have a higher chance of meeting dendritic cells, a type of immune cell that is scarce in the skin and muscles, but plays a key role in activating strong immune responses.
In a real-life scenario, genetically engineered proteins based on those displayed at the surface of pathogens would be freeze-dried or dehydrated and mixed with water, calcium and phosphate to make the nanoparticles. This should work with many different diseases and be especially useful for viral infections that are hard to vaccinate against, Baneyx said.
He cautioned, however, that the new technology has only been proven in mice. “It still has to be validated in humans and approved by the FDA, which takes much money and many years,” Baneyx explained to KurzweilAI.
“The approach could be useful in the future for vaccinating people in developing countries, especially when lead time and resources are scarce,” he added. “It would cut costs by not having to rely on refrigeration, and vaccines could be produced with rudimentary equipment in more precise, targeted numbers. The vaccines could be manufactured and delivered using a disposable patch, like a bandage, which could one day lessen the use of trained personnel and hypodermic needles.”
The research was funded by a Grand Challenges Explorations grant from the Bill & Melinda Gates Foundation and the National Institutes of Health.

Abstract of the Nanomedicine: Nanotechnology, Biology and Medicine paper
Distributed and on-demand vaccine production could be game-changing for infectious disease treatment in the developing world by providing new therapeutic opportunities and breaking the refrigeration “cold chain”. Here, we show that a fusion protein between a calcium phosphate binding domain and the model antigen ovalbumin can mineralize a biocompatible adjuvant in a single step. The resulting 50nm calcium phosphate core-immunogen shell particles are comparable to soluble protein in inducing ovalbumin-specific antibody response and class switch recombination in mice. However, single dose vaccination with nanoparticles leads to higher expansion of ovalbumin-specific CD8+ T cells upon challenge with an influenza virus bearing the ovalbumin-derived SIINFEKL peptide, and these cells produce high levels of IFN-γ. Furthermore, mice exhibit a robust antigen-specific CD8+ T cell recall response when challenged with virus 8months post-immunization. These results underscore the promise of immunogen-controlled adjuvant mineralization for just-in-time manufacturing of effective T cell vaccines.

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