Trend-Setter
6 years ago
*** Making vaccines immune to heat ***
Most vaccines need to be kept cool during transport and storage, but this can be hard to accomplish. EU-funded researchers keen to tackle this healthcare challenge have developed heat-tolerant and even needle-free formulations of an HIV-1 vaccine candidate. They expect their processes to work for many other vaccines as well.
Published: 30 October 2018
Related theme(s) and subtheme(s)
Health & life sciences : Drugs & drug processes | Medical research | Public health
Research policy : Horizon 2020
Countries involved in the project described in the article
Germany | Netherlands | Switzerland | United Kingdom
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© #191404568 | Author: EdNurg, 2018 fotolia.com
‘Many people are unaware that even short-time exposure is enough to damage the product,’ says Sylvain Fleury of Swiss biotechnology company Mymetics SA. A spoiled vaccine may not work, failing to offer the expected protection – and it might not actually be safe, he adds.
And yet, it is anything but rare for vaccine to be lost to this vulnerability. Cold chain breaches occur even in areas where the necessary logistics are available. They are an even greater risk in parts of the world that don’t benefit from this prerequisite.
Fleury is the initiator and scientific coordinator of MACIVIVA, an EU-funded project launched to bring vaccines in from the cold. Focusing on solid formulations holds the key, according to the partners involved in this endeavour backed by the EU and the Swiss government. The project is led by Mymetics SA’s Dutch sister company Mymetics BV.
The consortium is setting up pilot lines for the production of thermostable powder-based vaccines in the form of nasal sprays, oral capsules and sublingual tablets, as an alternative to heat-sensitive liquid vaccines. By the time MACIVIVA ends in November 2018, this task will be completed, Fleury reports.
The example on which the project focused is a vaccine candidate that could, one day, help to fight the AIDS epidemic. It targets HIV-1, the globally more common of the two types of HIV, Fleury notes. In addition to being more widespread than HIV-2, which is more specific to West Africa, HIV-1 is also generally more virulent, he adds.
Like most vaccines, the initial liquid formulation of this vaccine candidate had to be stored at 4 to 8 °C (no more, but no less either, to avoid damage from freezing). MACIVIVA’s solid formulations of this vaccine candidate have already been shown to be stable at temperatures of up to 40 °C for at least two months, Fleury reports, and studies covering even longer time spans are planned.
A solid solution
Commercial solid-form vaccines already exist, Fleury notes. However, these products also have to be cooled, he explains.
And many of these solid powder vaccines have to be reconstituted into a liquid before use. In contrast, the powder vaccines proposed by MACIVIVA are meant to be used straight out of the box.
The candidate vaccine taken forward by the project focused is based on influenza virosomes – particles derived from the membrane of dead flu viruses that can be filled or covered with substances used to treat or prevent disease.
Virosomes have no genetic material and are not infectious. They can’t replicate, but they can imitate: those used by MACIVIVA are, in effect, fake viruses dressed up as HIV-1. They are deployed to prompt the immune system into producing antibodies for protection.
MACIVIVA’s formulations are designed to do so where antibodies might be needed most urgently during the early stages of HIV infection, Fleury adds. Different types of immunisation – a nasal spray or a pill rather than an intramuscular jab, for example – could elicit immune responses of different strengths, in different parts of our body, he explains.
‘For HIV, it is important to induce antibodies not only in the blood, but also in the mucous membranes, where HIV-1 is likeliest to enter the body – more particularly, in the genital and intestinal tract,’ says Fleury. ‘Vaccine-induced mucosal antibodies could act as a front line defence.’
MACIVIVA’s alternative delivery forms are well suited to this purpose, Fleury adds. Connections within the immune system mean that nasal, oral and sublingual formulations can stimulate the production of mucosal antibodies in the targeted areas, he explains.[/color]
Look, no needles!
Administering MACIVIVA’s powder-based products wouldn’t require trained personnel. Once prescribed, vaccinations could be handled by the patients themselves, although supervision would be needed to ensure that they are carried out correctly, Fleury notes. Isolated communities without electricity in areas with patchy healthcare provision are not the only ones that would stand to benefit.
The HIV-1 vaccine candidate was developed by Mymetics prior to the project, Fleury explains. Results so far are very encouraging, he says, but trials and far more work will be required to turn it into a finished product, and funding for the next stages of the vaccine’s development has yet to be found.
The project has helped to take this particular vaccine forward, but this outcome, in a way, is icing on the cake. MACIVIVA focuses on the processes themselves, and it has developed solutions that could, in theory, also work for many other vaccines, Fleury notes – although adjustments would be needed for every new vaccine application.
MACIVIVA’s achievements build on excellent teamwork within the consortium, Fleury adds. Partners from three countries were involved, and most of them had never interacted before. ‘We all learned a lot from each other,’ he concludes.
Project details
Project acronym: MACIVIVA
Participants: Netherlands (Coordinator), Switzerland, United Kingdom, Germany
Project N°: 646122
Total costs: € 8 438 905
EU contribution: € 5 338 886
Duration: May 2015 to November 2018
http://ec.europa.eu/research/infocentre/article_en.cfm?artid=49737
Trend-Setter
6 years ago
New Mymetics Data Regarding Cold Chain Independent Virosome Based Vaccines to be Presented at AAPS in Washington, D.C.
-Poster presentation showing retention of structural integrity and good immunogenicity of spray dried virosome-based vaccine stored at different temperatures and administered as a nasal powder
-Poster presentation at AAPS - Washington, D.C., USA, Tuesday November 6th, 2018
The poster with the title "Developing Cold Chain Independent Vaccines - Spray-drying of Virosomes to Produce Dry Powder Formulations" will be presented by Dr. Richard Johnson, the CEO of Upperton Ltd, on Tuesday the 6th of November. Dr. Johnson will discuss that the successful spray drying of the Mymetics' HIV virosome-based candidate vaccine. The spray dried powder formulation stored at 4°C (40°F) or 40°C (104°F) maintained its structural integrity, while the liquid formulation showed strong structural degradation at 40°C (104°F). Further, a pre-clinical in vivo study confirmed that the nasal delivery of spray dried virosomes was an effective, needle-free route for immunization, with levels of immune response comparative to that obtained by subcutaneous injection.
Upperton Pharma Solutions Ltd., based in Nottingham, the United Kingdom, has a long track record in overcoming complex spray drying formulation challenges in the pharmaceutical industry and has an R&D and pilot plant facility for the manufacturing from small scale to clinical batches of spray dried drug substances and products.
The MACIVIVA project will end early November 2018 and may receive up to €5.3 million funding from the European Union's Horizon 2020 research and innovation program under Grant Agreement No 646122.
https://finance.yahoo.com/news/mymetics-data-regarding-cold-chain-133500521.html
Trend-Setter
7 years ago
Good News yesterday!
"Biohaven has been working with Catalent U.K. Swindon Zydis Limited, a subsidiary of Catalent, Inc. (NYSE: CTLT) ("Catalent") to develop a new ODT formulation of rimegepant which dissolves on the tongue without the need for fluid intake."
https://ih.advfn.com/p.php?pid=nmona&article=76833940
Same thing will happen to vaccines. Mymetics and 4 consortium partners are pioneering this disruptor in the vaccine industry worldwide.
"Vaccines are often produced as liquid biological products containing > 80% of water, which explains in part their instability during the storage in laboratories, hospitals, or manufacturing facilities. Liquid vaccines are inherently prone to physical and/or chemical modification, and degradation might also affect the immunological properties of the vaccine immunogens, with unwanted immune responses or insufficient immune protection. There is growing evidence that solid vaccine forms (e.g. powder) may offer several advantages over the liquid formulations, such as slowing down modifications and degradation.
The vaccine industry has developed freeze-drying lyophilization with low residual moisture content for improving stability and extending vaccine shelf-life. Such vaccines are stored as stable lyophilized dry products in a continuously frozen state at < -18°C, while others can be stored in refrigerators (+2-8°C). Therefore, maintenance of the cold chain is fundamental for preserving the bioactivity of most liquid and lyophilized vaccines currently on the market as well as those under development. However, many regions of developing countries also lack electricity and cooling capability for keeping vaccines below +8oC. The development of cold-chain independent vaccines in solid powder forms may greatly simplify the logistics and represent one of the long-term global solutions for addressing important issues faced by the vaccine field."
" Due to superior stability and the ease of administration of future solid vaccine forms for non-invasive routes, the world vaccine market landscape is expected to change. Thermostable solid vaccine forms developed for needle-free mucosal administration are expected to gradually replace the liquid and lyophilized/reconstituted vaccines administered by needle/syringe injections. Thus, such new thermostable solid vaccines will contribute to higher immunization coverage for the great benefit of the overall health care system."
https://cordis.europa.eu/result/rcn/194900_en.html
This project ends this year and final result is imminent!
Trend-Setter
7 years ago
Progress on MACIVIVA Project presented by consortium partner Upperton. "Spray drying of virosomes to produce stable vaccines"
Vaccines are poorly accessible in developing countries
Vaccines require cold-chain storage and are often delivered by injection, which is undesirable, less safe and more expensive to administer.
Developing thermostable solid form vaccines through non-invasive routes may represent a long-term global solution to the vaccination
challenge (Amorij, 2008)
Virosomes are an efficient vaccine delivery system
Virosomes are spherical, unilamellar lipid-based carriers, intercalated with functional glycoproteins to reflect the natural virus, however the lack
of viral RNA means there is no risk of infection (Figure 1). Virosomes can be tagged with different antigens and adjuvants, meaning they can
be tailored to target different viruses, and offer increased immunogenicity over inactivated viruses.
Currently, virosomal influenza vaccines are only available in liquid form (Amorij, 2008).
Spray drying can produce dry powders for a range of dosage forms, including inhaled or nasal drug delivery.
A dry powder is formed when a liquid feed solution or suspension is atomised using a spray nozzle, and rapidly dried using hot air. However,
while the drying process is gentle due to evaporative cooling, there is still the potential to stress and inactivate vaccine components. It has
been found that subunit and live-attenuated vaccines (and other delicate molecules such as proteins) can be protected during processing b
by incorporating them in an amorphous sugar matrix, which also offers longer term stability during storage (Kanojia, 2016)
A method has been developed to produce a powder form of virosome based influenza vaccine using spray-drying.
Formulations have been optimised for oral and nasal delivery.
http://www.upperton.com/images/pdf/t10.pdf
Trend-Setter
7 years ago
Mymetics to Present New Preclinical Data on Thermostable and Cold-Chain Independent Virosome based Vaccines
The new preclinical data will be presented at three upcoming events.
12 – 14 September, 2017: Modern Vaccines Adjuvants & Delivery Systems, Porto, Portugal.
16 – 18 September, 2017: ILS Liposome Advances & Liposome Research, Athens, Greece.
10 – 12 October, 2017: World Vaccine Congress Europe, Barcelona, Spain.
The preliminary results are showing that spray drying and lyophilization may conserve the virosome structure and antigens during the manufacturing process. Preclinical studies showed that Mymetics HIV-1 vaccine candidate, after being downstream processed into different powder solid dosage forms, could trigger specific antibodies, which were variable depending on the formulation. Antibodies were quantified in serum, nasal washes, vaginal washes and feces by the immuno-PCR Imperacer® assays.
https://www.otcmarkets.com/stock/MYMX/news/Mymetics-to-Present-New-Preclinical-Data-on-Thermostable-and-Cold-Chain-Independent-Virosome-based-Vaccines?id=169649&b=y
Trend-Setter
8 years ago
MACIVIVA = Game Changer
"Vaccines are often produced as liquid biological products containing > 80% of water, which explains in part their instability during the storage in laboratories, hospitals, or manufacturing facilities. Liquid vaccines are inherently prone to physical and/or chemical modification, and degradation might also affect the immunological properties of the vaccine immunogens, with unwanted immune responses or insufficient immune protection. There is growing evidence that solid vaccine forms (e.g. powder) may offer several advantages over the liquid formulations, such as slowing down modifications and degradation.
The vaccine industry has developed freeze-drying lyophilization with low residual moisture content for improving stability and extending vaccine shelf-life. Such vaccines are stored as stable lyophilized dry products in a continuously frozen state at < -18°C, while others can be stored in refrigerators (+2-8°C). Therefore, maintenance of the cold chain is fundamental for preserving the bioactivity of most liquid and lyophilized vaccines currently on the market as well as those under development. However, many regions of developing countries also lack electricity and cooling capability for keeping vaccines below +8oC. The development of cold-chain independent vaccines in solid powder forms may greatly simplify the logistics and represent one of the long-term global solutions for addressing important issues faced by the vaccine field."
"Furthermore, lyophilized vaccines must be reconstituted with a diluent prior to administration, which implies also that lyophilized vaccines must be packed and shipped together with vials/syringes containing the diluents for reconstitution. As most of the standard liquid vaccines, reconstituted lyophilized vaccines are generally administered intramuscularly, subcutaneously or intradermally with syringes. All the above suggests that liquid and freeze-dried vaccines, despite their good immunogenicity and stability, could be further improved by: i) Developing vaccines that are more thermostable, which means able to support high and low temperature excursions outside the recommended cold chain conditions or storage outside the cold chain; ii) Circumvent the powder reconstitution step prior administration; iii) Needle-free vaccination by one of the mucosal routes (sublingual, nasal or oral) with the solid vaccine powder forms."
"MACIVIVA Consortium has for main objective to develop robust “universal-like” manufacturing processes by heat spray drying or freeze-drying for obtaining new thermostable virosome dry powders for novel vaccine formulations for sublingual, oral and intranasal delivery, each representing a different manufacturing Pilot Line allowing GMP scale-up. If the project is successful, these thermostable virosomal vaccines could be stored outside the cold chain without affecting the vaccine properties, simplifying the logistics and addressing one of the major problems in the vaccine field. In the future, this may also allow the manufacturing of other human safe virosome-based vaccine formulations, as well as other vaccines. These innovative needle-free vaccines could be self-administered directly to the subject through the following non-invasive routes: Intranasal, oral and sublingual, without the need of reconstitution, favoring a broad acceptance in the target population."
"From May 2015 to October 2016 (M1-M18), all six MACIVIVA partners have closely collaborated together to achieve the project milestones and objectives set for this period. During the downstream processing from liquid to solid dosage forms, various analyses on virosomes were performed to make sure that they retain their original physical and biological properties after formulation as sublingual tablet, nasal spray and oral capsule. Mymetics SA had produced 12 different virosome fomulations during the first 18 months of the project, which were distributed among Upperton, Catalent, Chimera and Mymetics SA/BV. Catalent and Upperon have then evaluated various buffers and excipients for identifying the most suitable one for preserving the initial virosome structure, antigens and pH, respective to their own manufacturing process. Several manufacturing process parameters were investigated and optimized."
Full Coverage Report: http://cordis.europa.eu/result/rcn/194900_en.html
MACIVIVA : http://www.maciviva.eu/
Consortium partners:
http://www.mymetics.com/
http://www.catalent.com/index.php
http://www.bachem.com/
http://www.upperton.com/
http://www.chimera-biotec.com/
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