Tag Archives: Vaxxas

Preventing warmed-up vaccines from becoming useless

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.

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.

“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].

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.

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.

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.

Nanopatch more effective with poliovirus

No more needles or syringes that’s the Nanopatch promise and its one I’ve been writing about since 2009. It seems 2017 marks another step closer to seeing this idea become a product. From an Oct. 5, 2017 news item on ScienceDaily,

Efforts to rid the world of polio have taken another significant step, thanks to research led by University of Queensland [UQ] bioscience experts and funding from the World Health Organisation (WHO).

A fresh study of the Nanopatch — a microscopic vaccine delivery platform first developed by UQ researchers — has shown the device more effectively combats poliovirus than needles and syringes.

Here’s a prototype,

Caption: This is an image of the intended commercial product. Credit: Courtesy Vaxxas Pty Ltd

An Oct. 5, 2017 University of Queensland press release (also on EurekAlert), which originated the news item, provides more detail (Note: Links have been removed),

Head of UQ’s School of Chemistry and Molecular Biosciences Professor Paul Young said the breakthrough provided the next step in consigning polio to history.

“Polio was one of the most dreaded childhood diseases of the 20th century, resulting in limb disfigurement and irreversible paralysis in tens of millions of cases,” Professor Young said.

“This most recent study showed the Nanopatch enhanced responses to all three types of inactivated poliovirus vaccines (IPV) – a necessary advancement from using the current live oral vaccine.

“We are extremely grateful to the WHO for providing funding to Vaxxas Pty Ltd, the biotechnology company commercialising the Nanopatch.

“The support specifically assists pre-clinical studies and good manufacturing practices.”

Patch inventor Professor Mark Kendall said the study exhibited a key advantage of the Nanopatch.

“It targets the abundant immune cell populations in the skin’s outer layers, rather than muscle, resulting in a more efficient vaccine delivery system,” Professor Kendall said.

“The ease of administration, coupled with dose reduction observed in this study suggests that the Nanopatch could facilitate inexpensive vaccination of inactivated poliovirus vaccines.”

UQ Australian Institute for Biotechnology and Nanotechnology researcher Dr David Muller said effectively translating the dose could dramatically reduce the cost.

“A simple, easy-to-administer polio Nanopatch vaccine could increase the availability of the IPV vaccine and facilitate its administration in door-to-door and mass vaccination campaigns,” said Dr Muller.

“As recently as 1988, more than 350,000 cases occurred every year in more than 125 endemic countries.

“Concerted efforts to eradicate the disease have reduced incidence by more than 99 per cent.”

“Efforts are being intensified to eradicate the remaining strains of transmission once and for all.”

Data from the study encourages efforts by Vaxxas – established by UQ’s commercialisation company UniQuest – to bring the technology to use for human vaccinations.

“The research we are undertaking in conjunction with UQ and WHO can improve the reach of life-saving vaccines to children everywhere,” Vaxxas chief executive officer David Hoey said.

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

High-density microprojection array delivery to rat skin of low doses of trivalent inactivated poliovirus vaccine elicits potent neutralising antibody responses by David A. Muller, Germain J. P. Fernando, Nick S. Owens, Christiana Agyei-Yeboah, Jonathan C. J. Wei, Alexandra C. I. Depelsenaire, Angus Forster, Paul Fahey, William C. Weldon, M. Steven Oberste, Paul R. Young, & Mark A. F. Kendall. Scientific Reports 7, Article number: 12644 (2017) doi:10.1038/s41598-017-13011-0 Published online: 03 October 2017

This paper is open access.

Should you be interested in seeing previous posts, just use ‘Nanopatch’ as your search term in the blog search engine.

Australia’s nanopatch: a way to eliminate needle vaccinations

Tristan Clemons has written a Nov. 9, 2016 essay for The Conversation on one of my favourite stories, the nanopatch,

Who likes getting a needle? I know I definitely don’t.

Someone else who doesn’t is Mark Kendall from the University of Queensland, winner of the Young Florey Medal 2016.

Mark’s work in developing the nanopatch has provided a clear pathway for vaccine delivery science to move beyond 160 year-old needle and syringe technology.

… There are approximately 20,000 projections per square centimeter on each patch, each around 60 to 100 micrometres in length. One micrometre is one million times smaller than a metre, so the height of these tiny spikes is approximately the width of a human hair.

The nanopatch is produced using a technique known as “deep reactive ion etching”, which essentially makes use of ions (charged atoms) in an electric field to selectively etch the surface of a material away. Controlling the electric field and the ions allows a high degree of control, so the microprojections are regularly spaced and of similar dimensions.

An added advantage of this approach is it has been used in the electronic circuit and solar energy industries for many years, and has the potential for increasing the scale of production.

The tiny projections on each nanopatch are invisible to the naked eye, but are long enough to breach the outermost skin layer, the stratum corneum. The stratum corneum is a layer of dead skin cells which acts as the first barrier in protecting us from infection and skin water loss.

The nanopatch projections penetrate through the stratum corneum to reach the living skin layers directly below, the epidermis and the dermis. In the epidermis are several types of immune cells that are vital for the vaccine to work.

Hence the nanopatch is well suited to the delivery of vaccines where targeting immune cells is vital for vaccination success. Examples include influenza, polio and cholera.

Mark Kendall and his colleagues have shown they are able to coat nanopatch microprojections with a vaccine, apply the nanopatch to the skin and achieve vaccination with one tenth to one thirtieth of the dose required using traditional needle and syringe approaches.

… it’s more than just a good idea. Mark Kendall and his colleagues are now running human clinical trials of nanopatches in Brisbane, and the WHO is planning a polio vaccine trial in Cuba in 2017.

The latest information I have about this research is from a Feb. 26, 2016 University of Queensland press release,

Needle-free Nanopatch technology developed at The University of Queensland has been used to successfully deliver an inactivated poliovirus vaccine.

Delivery of a polio vaccine with the Nanopatch was demonstrated by UQ’s Professor Mark Kendall and his research team at UQ’s Australian Institute for Bioengineering and Nanotechnology, in collaboration with the World Health Organisation, the US Centres for Disease Control and Prevention, and vaccine technology company Vaxxas.

Professor Kendall said the Nanopatch had been used to administer an inactivated Type 2 poliovirus vaccine in a rat model.

“We compared the Nanopatch to the traditional needle and syringe, and found that there is about a 40-fold improvement in delivered dose-sparing,” Professor Kendall said.

“This means about 40 times less polio vaccine was needed in Nanopatch delivery to generate a functional immune response as the needle and syringe.

“To our knowledge, this is the highest level of dose-sparing observed for an inactivated polio vaccine in rats achieved by any type of delivery technology, so this is a key breakthrough.”

The next step will be clinical testing.

Dr David Muller, first author of the research published in Scientific Reports, said the work demonstrated a key advantage of the Nanopatch.

“The Nanopatch targets the abundant immune cell populations in the skin’s outer layers; rather than muscle, resulting in a more efficient vaccine delivery system,” he said.

Clinical success and widespread use of the Nanopatch against polio could help in the current campaign to eradicate polio. It could be produced and distributed at a cheaper cost, and its ease of use would make it suitable for house-to-house vaccination efforts in endemic areas with only minimal training required.

World Health Organisation Global Polio Eradication Initiative Director Mr Michel Zaffran said only Afghanistan and Pakistan remained polio-endemic, but all countries were at risk until the disease was eradicated everywhere.

“Needle-free microneedle patches such as the Nanopatch offer great promise for reaching more children with polio vaccine as well as other antigens such as measles vaccine, particularly in hard-to-reach areas or areas with inadequate healthcare infrastructure,” Mr Zaffran said.

Nanopatch technology is being commercialised by Vaxxas Pty Ltd, which has scaled the Nanopatch from use in small models to prototypes for human use.

Vaxxas CEO Mr David Hoey said the first human vaccination studies are scheduled for this year [2016].

“Key attributes of the Nanopatch, including its ease of use and potential to not require refrigeration, could improve the reach and efficiency of vaccination campaigns in difficult-to-reach locations, including those where polio remains endemic,” Mr Hoey said.

The work was funded by the World Health Organisation, Vaxxas, Rotary District 9630 and the Rotary Foundation.

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

Inactivated poliovirus type 2 vaccine delivered to rat skin via high density microprojection array elicits potent neutralising antibody responses by David A. Muller, Frances E. Pearson, Germain J.P. Fernando, Christiana Agyei-Yeboah, Nick S. Owens, Simon R. Corrie, Michael L. Crichton, Jonathan C.J. Wei, William C. Weldon, M. Steven Oberste, Paul R. Young, & Mark A. F. Kendall. Scientific Reports 6, Article number: 22094 (2016) doi:10.1038/srep22094 Published online: 25 February 2016

This paper is open access.

As befitting a ‘favourite story’, I’ve been following it for a number of years starting with this April 23, 2009 posting (scroll down about 25% of the way) although you might prefer to read this more substantive July 26, 2010 posting. The last time (Aug. 3, 2011 posting) I featured the story, it was to announce an investment of AUD $15M in Vaxxas (Kendall is not listed as member of the company) in order to bring the nanopatch to market.