Tag Archives: PRINT® (Particle Replication In Non-Wetting Templates) technology

Nanotechnology-enabled dengue virus vaccine

Here’s news of work-in-progress for a dengue virus vaccine and, possibly, a Zika virus vaccine too. From a Nov. ??, 2016 University of North Carolina news release,

Scientists at the UNC School of Medicine are working to develop a nanoparticle vaccine to protect against the four serotypes of dengue virus, which infects more than 350 million people across the globe each year.

Aravinda de Silva, PhD, professor of microbiology and immunology, and a post-doctoral researcher Stefan Metz, PhD, recently published the latest on their vaccine development efforts in PLOS Neglected Tropical Diseases.

The nanoparticle platform was produced with PRINT (Particle Replication in Non-wetting Templates) technology. Joseph DeSimone, PhD, the Chancellor’s Eminent Professor of Chemistry and a joint professor in the Department of Pharmacology at UNC, developed PRINT, a nano-molding technique, in 2004.

Rather than using a killed or attenuated virus to develop a vaccine for dengue, de Silva’s lab is focusing on “expressing the E protein and attaching it to nanoparticles to induce good immune responses,” Metz said.

The nanoparticle vaccine platform can be safer to certain populations than vaccines that use either live or killed virus, he said.

One of the many complexities about developing a successful dengue vaccine, Metz explained, is that there are four serotypes of the virus, which means researchers need to develop a vaccine that provides immunity against all four serotypes.

“There are currently several vaccines in trial and development for dengue,” Metz said. “One vaccine has gone through all three clinical trial phases and has been licensed in some countries. Although these vaccines produce good antibody responses, a large part of the population still wasn’t protected from each of the serotypes.

“With dengue, you need to vaccinate people against all four serotypes at once in order to protect people. That’s why we’re combing the different serotypes.”

In their most recent study, de Silva and Metz focused their efforts on the second serotype. Now, they’re moving forward with the same studies for serotypes one, three and four.

“In the study, we express the E protein, which is found on the surface of the virus particle,” Metz explained. “This protein is organized in a very complex way, and this complex organization exposes isotopes that are important to induce protective immune response.”

De Silva and Metz were recently named to a global research consortium to tackle Zika, and they’re using the same nanoparticle vaccine platform as they work to develop a Zika vaccine.

“Globally, if you look at the numbers, dengue is still a much bigger problem than Zika,” Metz said, noting that an estimated 25,000 people die from dengue infections each year. “If you get dengue, you might not even notice it. If you do get clinical symptoms during a first infection of dengue, you might feel like you have a feverish flu. A lot of people don’t even know it because if you’re not feeling well for a couple days, you don’t necessarily think that it’s caused by a dengue virus infection.

“However, if you were infected by the first serotype and you had a secondary infection with a different serotype, that’s when the more severe diseases can come up – stress syndromes, hemorrhagic diseases – those can be fatal diseases,” Metz said. “There are thousands and thousands of people dying from those diseases each year.”

Here’s a link to and a citation for the paper,

Precisely Molded Nanoparticle Displaying DENV-E Proteins Induces Robust Serotype-Specific Neutralizing Antibody Responses by Stefan W. Metz, Shaomin Tian, Gabriel Hoekstra, Xianwen Yi, Michelle Stone, Katie Horvath, Michael J. Miley, Joseph DeSimone, Chris J. Luft, Aravinda M. de Silva. PLOS http://dx.doi.org/10.1371/journal.pntd.0005071  Published: October 20, 2016

This paper is open access.

GlaxoSmithKline (with roots in the 18th century) makes 21st century deal with Liquidia Technologies

The GlaxoSmithKline (GSK) company history starts in the 1700s (1715 to be exact) when “Plough Court pharmacy, the forerunner of Allen and Hanburys Ltd, is established in London by Silvanus Bevan” (from the Company History webpage). As you’ve probably guessed, GSK is a pharmaceutical company (from the About Us, Our Company page),

We are a science-led global healthcare company

We have a challenging and inspiring mission: to improve the quality of human life by enabling people to do more, feel better and live longer. This mission gives us the purpose to develop innovative medicines and products that help millions of people around the world.

Headquartered in the UK, we are a global organisation with offices in over 100 countries and major research centres in the UK, USA, Spain, Belgium and China.

But being a leader brings responsibility. This means that we care about the impact that we have on the people and places touched by our mission to improve health around the world.

It also means that we must help developing countries where debilitating disease affects millions of people and access to life-changing medicines and vaccines is a problem. To meet this challenge, we are committed to providing discounted medicines where they are needed the most.

We are one of the few healthcare companies researching both medicines and vaccines for the World Health Organization’s three priority diseases – HIV/AIDS, tuberculosis and malaria, and are very proud to have developed some of the leading global medicines in these fields.

We produce medicines that treat major disease areas such as asthma, anti-virals, infections, mental health, diabetes, cardiovascular and digestive conditions. In addition, we are a leader in the important area of vaccines and are developing new treatments for cancer.

We also market other consumer products, many of which are among the market leaders:

  • over-the-counter (OTC) medicines including Gaviscon and Panadol
  • dental products such as Aquafresh and Sensodyne
  • smoking control products Nicorette/Niquitin
  • nutritional healthcare drinks such as Lucozade, Ribena and Horlicks skincare products marketed by Stiefel Laboratories

The other partner in this deal, nanomedicine company  Liquidia Technologies offers a less expansive description of their healthcare interests while a more market-oriented approach (from the home page),

Over the next decade, nanotechnology has the potential to influence virtually every aspect of our lives, including our energy, food, water, buildings, and medicines. According to a recently published report by BCC Research, the market value of the worldwide nanomedicine industry alone is estimated to grow at a CAGR [compound annual growth rate] of 12.5% to reach $130.9 billion by the fiscal year 2016. However, in order to realize this broad potential robust, cost-effective, regulatory-friendly manufacturing technologies will be required. Through its novel nanoparticle technology platform and expansive intellectual property, Liquidia is poised to be a leader in the development of nanotechnology-based healthcare products and a catalyst for the growth anticipated across this industry.

Here’s more about the deal and the technology, from the June 20,2012 news item on Nanowerk,

Liquidia Technologies today announced the initiation of a broad, multi-year collaboration with GlaxoSmithKline (GSK), which has acquired exclusive rights to research and develop certain vaccine and inhaled product candidates using the company’s proprietary PRINT® (Particle Replication In Non-Wetting Templates) technology. Liquidia’s PRINT technology is a powerful and versatile nanoparticle technology product development and manufacturing platform that is changing the way companies engineer healthcare products.

“We are very pleased to have the opportunity to work with GSK, a company known for its commitment to scientific excellence, medicinal chemistry expertise and expansive library of proprietary compounds that could potentially benefit from Liquidia’s PRINT technology,” said Neal Fowler, Chief Executive Officer at Liquidia, “The strength of this collaboration is based on the strong and successful heritage of GSK’s vaccine and inhaled therapy franchises and the transformative particle engineering and manufacturing capabilities of Liquidia’s PRINT technology, which when combined, we believe will yield a next generation of life saving therapeutics.”

Here’s my description of Liquidia’s PRINT technology (it’s not possible to cut and past from the company’s Product Platform page). The company has copied lithographic techniques used in the semiconductor industry to develop templates, probably polymer-based, that look like cupcake tins to me. Somehow a bunch of dots (nanoparticles) are attracted to these cupcake tin moulds, which can be different shapes, and somehow the nanoparticles are induced to remain in the shape prescribed by the mould as it disintegrates leaving the newly moulded nanoparticle shape ready for use.

Here’s more from the June 20, 2012 news item,

According to the agreement, Liquidia will receive an upfront payment, comprised of cash and equity, R&D funding, as well as potential for additional licensing fees, development milestones, and royalties. Upfront payment, R&D funding, licensing, and development and regulatory milestone payments under this collaboration could total up to several hundred million dollars upon all contingent payments coming due. Through this agreement, Liquidia has also retained the ability to independently develop certain respiratory and vaccine products in addition to using the PRINT platform to develop products in other therapeutic areas.

It certainly seems as if Liquidia Technologies (the source for the June 20, 2012 news item)  is more interested in communicating about business and markets than about any health benefits for the rest of us.