Tag Archives: Merck

Preventing warmed-up vaccines from becoming useless

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One of the major problems with vaccines is that they need to be refrigerated. (The Nanopatch, which additionally wouldn’t require needles or syringes, is my favourite proposed solution and it comes from Australia.) This latest research into making vaccines more long-lasting is from the UK and takes a different approach to the problem.

From a June 8, 2020 news item on phys.org,

Vaccines are notoriously difficult to transport to remote or dangerous places, as they spoil when not refrigerated. Formulations are safe between 2°C and 8°C, but at other temperatures the proteins start to unravel, making the vaccines ineffective. As a result, millions of children around the world miss out on life-saving inoculations.

However, scientists have now found a way to prevent warmed-up vaccines from degrading. By encasing protein molecules in a silica shell, the structure remains intact even when heated to 100°C, or stored at room temperature for up to three years.

The technique for tailor-fitting a vaccine with a silica coat—known as ensilication—was developed by a Bath [University] team in collaboration with the University of Newcastle. This pioneering technology was seen to work in the lab two years ago, and now it has demonstrated its effectiveness in the real world too.

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Here’s the lead researcher describing her team’s work

Ensilication: success in animal trials from University of Bath on Vimeo.

A June 8, 2020 University of Bath press release (also on EurekAlert) fills in more details about the research,

In their latest study, published in the journal Scientific Reports, the researchers sent both ensilicated and regular samples of the tetanus vaccine from Bath to Newcastle by ordinary post (a journey time of over 300 miles, which by post takes a day or two). When doses of the ensilicated vaccine were subsequently injected into mice, an immune response was triggered, showing the vaccine to be active. No immune response was detected in mice injected with unprotected doses of the vaccine, indicating the medicine had been damaged in transit.

Dr Asel Sartbaeva, who led the project from the University of Bath’s Department of Chemistry, said: “This is really exciting data because it shows us that ensilication preserves not just the structure of the vaccine proteins but also the function – the immunogenicity.”

“This project has focused on tetanus, which is part of the DTP (diphtheria, tetanus and pertussis) vaccine given to young children in three doses. Next, we will be working on developing a thermally-stable vaccine for diphtheria, and then pertussis. Eventually we want to create a silica cage for the whole DTP trivalent vaccine, so that every child in the world can be given DTP without having to rely on cold chain distribution.”

Cold chain distribution requires a vaccine to be refrigerated from the moment of manufacturing to the endpoint destination.

Silica is an inorganic, non-toxic material, and Dr Sartbaeva estimates that ensilicated vaccines could be used for humans within five to 15 years. She hopes the technology to silica-wrap proteins will eventually be adopted to store and transport all childhood vaccines, as well as other protein-based products, such as antibodies and enzymes.

“Ultimately, we want to make important medicines stable so they can be more widely available,” she said. “The aim is to eradicate vaccine-preventable diseases in low income countries by using thermally stable vaccines and cutting out dependence on cold chain.”

Currently, up to 50% of vaccine doses are discarded before use due to exposure to suboptimal temperatures. According to the World Health Organisation (WHO), 19.4 million infants did not receive routine life-saving vaccinations in 2018.

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

Ensilicated tetanus antigen retains immunogenicity: in vivo study and time-resolved SAXS characterization by A. Doekhie, R. Dattani, Y-C. Chen, Y. Yang, A. Smith, A. P. Silve, F. Koumanov, S. A. Wells, K. J. Edler, K. J. Marchbank, J. M. H. van den Elsen & A. Sartbaeva. Scientific Reports volume 10, Article number: 9243 (2020) DOI: https://doi.org/10.1038/s41598-020-65876-3 Published 08 June 2020

This paper is open access

Nanopatch update

I tend to lose track as a science gets closer to commercialization since the science news becomes business news and I almost never scan that sector. It’s been about two-and-half years since I featured research that suggested Nanopatch provided more effective polio vaccination than the standard needle and syringe method in a December 20, 2017 post. The latest bits of news have an interesting timeline.

March 2020

Mark Kendal (Wikipedia entry) is the researcher behind the Nanopatch. He’s interviewed in a March 5, 2020 episode (about 20 mins.) in the Pioneers Series (bankrolled by Rolex [yes, the watch company]) on Monocle.com. Coincidentally or not, a new piece of research funded by Vaxxas (the nanopatch company founded by Mark Kendall; on the website you will find a ‘front’ page and a ‘Contact us’ page only) was announced in a March 17, 2020 news item on medical.net,

Vaxxas, a clinical-stage biotechnology company commercializing a novel vaccination platform, today announced the publication in the journal PLoS Medicine of groundbreaking clinical research indicating the broad immunological and commercial potential of Vaxxas’ novel high-density microarray patch (HD-MAP). Using influenza vaccine, the clinical study of Vaxxas’ HD-MAP demonstrated significantly enhanced immune response compared to vaccination by needle/syringe. This is the largest microarray patch clinical vaccine study ever performed.

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“With vaccine coated onto Vaxxas HD-MAPs shown to be stable for up to a year at 40°C [emphasis mine], we can offer a truly differentiated platform with a global reach, particularly into low and middle income countries or in emergency use and pandemic situations,” said Angus Forster, Chief Development and Operations Officer of Vaxxas and lead author of the PLoS Medicine publication. “Vaxxas’ HD-MAP is readily fabricated by injection molding to produce a 10 x 10 mm square with more than 3,000 microprojections that are gamma-irradiated before aseptic dry application of vaccine to the HD-MAP’s tips. All elements of device design, as well as coating and QC, have been engineered to enable small, modular, aseptic lines to make millions of vaccine products per week.”

The PLoS publication reported results and analyses from a clinical study involving 210 clinical subjects [emphasis mine]. The clinical study was a two-part, randomized, partially double-blind, placebo-controlled trial conducted at a single Australian clinical site. The clinical study’s primary objective was to measure the safety and tolerability of A/Singapore/GP1908/2015 H1N1 (A/Sing) monovalent vaccine delivered by Vaxxas HD-MAP in comparison to an uncoated Vaxxas HD-MAP and IM [intramuscular] injection of a quadrivalent seasonal influenza vaccine (QIV) delivering approximately the same dose of A/Sing HA protein. Exploratory outcomes were: to evaluate the immune responses to HD-MAP application to the forearm with A/Sing at 4 dose levels in comparison to IM administration of A/Sing at the standard 15 μg HA per dose per strain, and to assess further measures of immune response through additional assays and assessment of the local skin response via punch biopsy of the HD-MAP application sites. Local skin response, serological, mucosal and cellular immune responses were assessed pre- and post-vaccination.

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

Safety, tolerability, and immunogenicity of influenza vaccination with a high-density microarray patch: Results from a randomized, controlled phase I clinical trial by Angus H. Forster, Katey Witham, Alexandra C. I. Depelsenaire, Margaret Veitch, James W. Wells, Adam Wheatley, Melinda Pryor, Jason D. Lickliter, Barbara Francis, Steve Rockman, Jesse Bodle, Peter Treasure, Julian Hickling, Germain J. P. Fernando. DOI: https://doi.org/10.1371/journal.pmed.1003024 PLOS (Public Library of Science) Published: March 17, 2020

This is an open access paper.

May 2020

Two months later, Merck, an American multinational pharmaceutical company, showed some serious interest in the ‘nanopatch’. A May 28, 2020 article by Chris Newmarker for drugdelvierybusiness.com announces the news (Note: Links have been removed),

Merck has exercised its option to use Vaxxas‘ High Density Microarray Patch (HD-MAP) platform as a delivery platform for a vaccine candidate, the companies announced today [Thursday, May 28, 2020].

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Also today, Vaxxas announced that German manufacturing equipment maker Harro Höfliger will help Vaxxas develop a high-throughput, aseptic manufacturing line to make vaccine products based on Vaxxas’ HD-MAP technology. Initial efforts will focus on having a pilot line operating in 2021 to support late-stage clinical studies — with a goal of single, aseptic-based lines being able to churn out 5 million vaccine products a week.

“A major challenge in commercializing microarray patches — like Vaxxas’ HD-MAP — for vaccination is the ability to manufacture at industrially-relevant scale, while meeting stringent sterility and quality standards. Our novel device design along with our innovative vaccine coating and quality verification technologies are an excellent fit for integration with Harro Höfliger’s aseptic process automation platforms. Adopting a modular approach, it will be possible to achieve output of tens-of-millions of vaccine-HD-MAP products per week,” Hoey [David L. Hoey, President and CEO of Vaxxas] said.

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Vaxxas also claims that the patches can deliver vaccine more efficiently — a positive when people around the world are clamoring for a vaccine against COVID-19. The company points to a recent [March 17, 2020] clinical study in which their micropatch delivering a sixth of an influenza vaccine dose produced an immune response comparable to a full dose by intramuscular injection. A two-thirds dose by HD-MAP generated significantly faster and higher overall antibody responses.

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As I noted earlier, this is an interesting timeline.

Final comment

In the end, what all of this means is that there may be more than one way to deal with vaccines and medicines that deteriorate all too quickly unless refrigerated. I wish all of these researchers the best.

Queen’s University (Belfast) and ionic liquid chemistry voted the most important British innovation of the 21st Century

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Given all the excitement about graphene these days, one might expect that it would be voted the ‘most important British innovation of the 21st Century’. In a surprise move, ionic liquid chemistry has achieved that title according to a Mar. 27, 2013 news item on Azonano,

The work of staff in the Queen’s University Ionic Liquid Laboratories (QUILL) Research Centre has been named as the innovation that will have the greatest impact in the coming Century.

QUILL fought off stiff competition from 11 other innovations from across the United Kingdom to win the vote which was part of the Science Museum’s Initiative on Great British past and future Innovations. This initiative was also sponsored, amongst others, by: Engineering UK, The Royal Society, British Science Association, Royal Academy of Engineering and Department for Business Innovation & Skills

A team of nearly 100 scientists are exploring the potential of ionic liquids at Queen’s. Known as ‘super solvents’, they are salts that remain liquid at room temperature and do not form vapours. They can be used as non-polluting alternatives to conventional solvents and are revolutionising chemical processes by offering a much more environmentally friendly solution than traditional methods.

The Queen’s University Mar. 26?, 2013 news release provides more information,

Professor Ken Seddon is Co-Director of QUILL. His seminal paper started the world-wide surge of interest in ionic liquids and it has now reached over 1000 citations. Speaking about their latest achievement, he said: “We are delighted to win as this shines a very public spotlight on how a team of chemists can dramatically improve the quality of the environment for everyone. Being named the most important British innovation of the 21st Century is recognition of the high calibre of research being undertaken at QUILL and throughout the University.”

Professor Jim Swindall, Co-Director of QUILL at Queen’s, said: “This is fantastic news for QUILL and for the University. This vote confirms that Queen’s work on ionic liquid chemistry will eventually have a bearing on most of our lives. The liquids dissolve almost everything, from elements such as sulfur and phosphorus (that traditionally require nasty solvents) to polymers, including biomass. They can even remove bacterial biofilms such as MRSA. They are already being used in a process to remove mercury from natural gas by Petronas in Malaysia. Others can be used as heat pumps, compression fluids, or lubricants – the list is limitless.”

Enterprise Minister Arlene Foster said: “I congratulate Queen’s University on winning this most prestigious of accolades. It is a great achievement for Professors Ken Sedden and Jim Swindall and the entire team at QUILL and it is a great day for Northern Ireland science. This recognition underlines the strength of research being undertaken by Queen’s and the impact this research has on the chemical and environmental industry around the world.”

Robin Swann, Chairman of the Northern Ireland Assembly’s Committee for Employment and Learning said: “The result of this public vote is terrific news for Northern Ireland as it demonstrates the importance of the research being undertaken at Queen’s. The fact that global energy giant Petronas is already using the technology in its plants demonstrates the value and global impact of the research at the University and I congratulate Queen’s on this significant achievement.”

Set up in 1999, QUILL is an industry/university cooperative research centre and is now a world leader in the creation of ionic liquids. Key industry partners include BASF, Chevron, Invista, Merck, Petronas, Proctor & Gamble and Shell.

Congratulations to the folks at QUILL!

More on quantum dots: a toxicity study; Merck action in Israel

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I have two items on quantum dots today. The first concerns a toxicity study performed on primates at the University of Buffalo (NY, USA). From the May 22, 2012 news item by Will Soutter for Azonano,

A multi-institute toxicity study on quantum dots in primates has discovered that these nanocrystals are safe for a period of one year.

This finding is encouraging for researchers and physicians looking for novel techniques to treat diseases such as cancer using nanomedicine. The organizations involved in the study included the University at Buffalo, Nanyang Technological University, ChangChun University of Science and Technology, and the Chinese PLA General Hospital.

On digging a little further, I found this information on the University of Buffalo website, from their May 21, 2012 news release,

— Tiny luminescent crystals called quantum dots hold great promise as tools for treating and detecting diseases like cancer.

— A pioneering study to gauge the toxicity of quantum dots in primates has found cadmium-selenide quantum dots to be safe over intervals of time ranging from three months to a year. The study is likely the first to test the safety of quantum dots in primates.

— The authors say more research is needed to determine quantum dots’ long-term effect on health; elevated levels of cadmium from the quantum dots were found in the primates even after 90 days.

The research, which appeared on May 20 in Nature Nanotechnology online , is likely the first to test the safety of quantum dots in primates.

In the study, scientists found that four rhesus monkeys injected with cadmium-selenide quantum dots remained in normal health over 90 days. Blood and biochemical markers stayed in typical ranges, and major organs developed no abnormalities. The animals didn’t lose weight.

Two monkeys observed for an additional year also showed no signs of illness.

The first  results are hopeful but there are some concerns,

The new toxicity study — completed by the University at Buffalo, the Chinese PLA General Hospital, China’s ChangChun University of Science and Technology, and Singapore’s Nanyang Technological University — begins to address the concern of health professionals who worry that quantum dots may be dangerous to humans.

The authors caution, however, that more research is needed to determine the nanocrystals’ long-term effects in primates; most of the potentially toxic cadmium from the quantum dots stayed in the liver, spleen and kidneys of the animals studied over the 90-day period.

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The cadmium build-up, in particular, is a serious concern that warrants further investigation, said Ken-Tye Yong, a Nanyang Technological University assistant professor who began working with Prasad [Paras N. Prasad] on the study as a postdoctoral researcher at UB.

Unusually, this article seems to be open access at Nature Nanotechnology,

A pilot study in non-human primates shows no adverse response to intravenous injection of quantum dots

Ling Ye, Ken-Tye Yong, Liwei Liu, Indrajit Roy, Rui Hu, Jing Zhu, Hongxing Cai, Wing-Cheung Law, Jianwei Liu, Kai Wang, Jing Liu, Yaqian Liu, Yazhuo Hu, Xihe Zhang, Mark T. Swihart, and Paras N. Prasad

Nature Nanotechnology (2012) doi:10.1038/nnano.2012.74

The acquisition of an Israeli quantum dot company by Merck is my second bit of quantum dot news, from the May 22, 2012 news item on Nanowerk,

Merck announced today that within the scope of a capital increase by the Israeli start-up company QLight Nanotech, it is acquiring an interest in the Jerusalem-based company. QLight Nanotech is a spin-off subsidiary of Yissum, the technology transfer company of the Hebrew University of Jerusalem. QLight Nanotech develops products for use in displays and energy-efficient light sources based on semiconductor nanoparticles known as quantum dots.

I understood that Merck was a pharmaceutical company so I was bit surprised to see this (from the May 22, 2012 news item on the Solid State Technology website)

“I am excited that our basic science discoveries on semiconductor nanocrystals are now being realized in innovative technological applications. The partnership with Merck, a world leader in materials for display applications, is a synergistic one allowing us at Qlight Nanotech to implement advanced chemicals manufacturing and applications’ know-how,” said the scientific founder of  QLight Nanotech, Professor Uri Banin of the Hebrew University of Jerusalem, who will continue to support the company as a shareholder and advisor alongside of Yissum.

In fact, Merck bills itself as a pharmaceuticals and a s chemicals company.