You Will Get Your Plant Derived Vaccines Explained in 12 Minutes Or Death 2 You ?

PMI Announces Medicago to Supply Up to 76 Million Doses of Its Plant-Derived COVID-19 Vaccine Candidate A Philip Morris International subsidiary is a shareholder in a biopharmaceutical company that reached agreements with two departments of the Canadian government to accelerate its COVID-19 vaccine candidate efforts. Since 2008, Philip Morris Investments B.V. (PMIBV), a subsidiary of Philip Morris International (PMI) (NYSE: PM), has been a shareholder of Medicago (in which it currently holds an approximately one-third equity stake) and has supported Medicago’s innovative plant-derived research and development focused on vaccines. The investment is consistent with PMI’s own efforts to leverage science and innovation. Japan-based Mitsubishi Tanabe Pharma Corporation (MTPC) is the majority shareholder and PMIBV’s partner in Medicago. Among other things, PMIBV and MTPC will contribute additional funding to support Medicago’s efforts to develop a COVID-19 vaccine candidate.Show more

Medicago, a biopharmaceutical company headquartered in Quebec City, announced that it reached an agreement with Public Services and Procurement Canada (PSPC) to supply up to 76 million doses of its vaccine candidate for COVID-19, subject to Health Canada approval. Innovation, Science & Economic Development (ISED), another department of the Canadian federal government, will contribute C$173M (or approximately $131M) to Medicago to support its on-going vaccine development and clinical trials, and for the construction of its Quebec City manufacturing facility.

PMI’s CEO André Calantzopoulos said: “We welcome the collaboration announced between two departments of the Canadian government and Medicago to accelerate its efforts against COVID-19. Better outcomes can be achieved when governments and companies join efforts to promote shared objectives for the greater good. We are pleased to be able to support Medicago’s work to develop, substantiate, manufacture, and make available a COVID-19 vaccine candidate. We all hope they will be successful.”

Medicago began Phase 1 testing on volunteers on July 14 and is anticipating that Phase 2 trials will begin in early November 2020. If Phase 2 trials are successful, Phase 3 trials are expected to begin in December 2020.

Philip Morris International: Delivering a Smoke-Free Future

Philip Morris International (PMI) is leading a transformation in the tobacco industry to create a smoke-free future and ultimately replace cigarettes with smoke-free products to the benefit of adults who would otherwise continue to smoke, society, the company, and its shareholders. PMI is a leading international tobacco company engaged in the manufacture and sale of cigarettes, as well as smoke-free products and associated electronic devices and accessories, and other nicotine-containing products in markets outside the U.S. In addition, PMI ships a version of its IQOS Platform 1 device and its consumables to Altria Group, Inc. for sale under license in the U.S., where the U.S. Food and Drug Administration (FDA) has authorized their marketing as a modified risk tobacco product (MRTP), finding that an exposure modification order for these products is appropriate to promote the public health. PMI is building a future on a new category of smoke-free products that, while not risk-free, are a much better choice than continuing to smoke. Through multidisciplinary capabilities in product development, state-of-the-art facilities, and scientific substantiation, PMI aims to ensure that its smoke-free products meet adult consumer preferences and rigorous regulatory requirements. PMI’s smoke-free product portfolio includes heat-not-burn and nicotine-containing vapor products. As of September 30, 2020, PMI estimates that approximately 11.7 million adult smokers around the world have already stopped smoking and switched to PMI’s heat-not-burn product, available for sale in 61 markets in key cities or nationwide under the IQOS brand. Medicago signs agreements with the government of Canada to supply up to 76 million doses of its recombinant plant-derived COVID-19 vaccine.

Quebec, October 23, 2020 – Medicago, a biopharmaceutical company headquartered in Quebec City, is pleased to announce that it has reached an agreement to supply the Government of Canada with up to 76 million doses of its vaccine against COVID-19, subject to Health Canada approval. Medicago will also receive $173M in funding support from the Government of Canada for its vaccine research and development, and for the construction of its Quebec City manufacturing facility.

“We are proud to contribute a made-in-Canada vaccine to our country’s vaccine supply, and we want to thank the Government of Canada for its confidence in Medicago,” said Dr. Bruce Clark, President and CEO of Medicago.

Medicago’s innovative plant-based platform is a powerful tool that is being used to develop and, upon regulatory approval, produce vaccines helping to increase Canada’s self-reliance for pandemic response. The government’s investment not only supports Medicago’s research and innovation, but it also reinforces the Canadian economy, our scientific ecosystem and our domestic pandemic response capabilities.

“Our government is committed to protecting the health and safety of Canadians,” said the Honourable Navdeep Bains, Minister of Innovation, Science and Industry. “Today’s contribution will support breakthrough Canadian technology to advance the development of a vaccine for COVID-19 and support biomanufacturing capacity for a Made-in-Canada solution.”

“This agreement between the Government of Canada and Medicago ensures that Canadians will have access to another promising COVID-19 vaccine candidate. Medicago is working diligently right here in Canada to support the response to COVID-19 and protect the health and safety of Canadians,” said the Honourable Anita Anand, Minister of Public Services and Procurement.

“Medicago’s team is committed to being part of the global effort to fight the COVID-19 pandemic, and we look forward to the day where our vaccine is approved and we are supplying it both in Canada, and beyond our borders” said Clark.

On March 12, Medicago announced the successful production of coronavirus Virus-Like Particle (VLP) in just 20 days after receiving the virus gene, thus having a viable vaccine candidate for COVID-19. Medicago initiated pre-clinical trials with the financial support from the Government of Quebec and began Phase 1 testing on July 14 in human volunteers. Medicago plans to initiate Phase 2 trials in early November, and Phase 3 trials shortly after, in December 2020.

“We are confident that our vaccine candidate will succeed, and we look forward to communicating Phase 1 results in the coming weeks.” said Nathalie Landry, Executive Vice President, Scientific and Medical Affairs at Medicago.

Medicago’s first product, a seasonal recombinant quadrivalent VLP vaccine for active immunization against influenza, is currently under review by Health Canada following the completion of an extensive safety and efficacy clinical program involving over 25,000 patients.

Medicago is grateful for the financial support of its main shareholder, Mitsubishi Tanabe Pharma Corporation (MTPC), and minority shareholder, Philip Morris International (PMI).

Medicago is a biopharmaceutical company and pioneer in plant-based therapeutics technology. Founded in 1999 with the belief that innovative approaches and rigorous research would bring new solutions in healthcare.

Our mission is to improve global health outcomes by leveraging innovative plant-based technologies for rapid responses to emerging global healthcare challenges. Medicago is committed to advancing therapeutics against life-threatening diseases worldwide. Our team includes over 450 scientific experts and employees in Canada and the United States and academic affiliations in Europe and South Africa.

Medicago has previously demonstrated its capability to be a first responder in a flu pandemic. In 2009, the company produced a research-grade vaccine candidate against H1N1 in just 19 days. In 2012, Medicago manufactured 10 million doses of a monovalent influenza vaccine candidate within one month for the Defense Advanced Research Projects Agency (DARPA), part of the U.S. Department of Defense. In 2015, Medicago also demonstrated in principle that it could rapidly produce an anti-Ebola monoclonal antibody cocktail for the Biomedical Advanced Research and Development Authority (BARDA), part of the U.S. Department of Health and Human Services.

The Biomedical Advanced Research and Development Authority (BARDA), within the Administration for Strategic Preparedness and Response (ASPR) in the U.S. Department of Health and Human Services, provides an integrated, systematic approach to the development of the necessary vaccines, drugs, therapies, and diagnostic tools for public health medical emergencies such as chemical, biological, radiological, and nuclear (CBRN) accidents, incidents and attacks, pandemic influenza, and emerging infectious diseases. Together with our industry partners, BARDA promotes the advanced development of medical countermeasures to protect Americans and respond to 21st century health security threats.

Project BioShield adds Ebola vaccines, drugs to US stockpile The US Department of Health and Human Services (HHS) has announced the first Project BioShield funding for Ebola countermeasures, which would add two vaccines and two treatments to the Strategic National Stockpile (SNS): a single-dose vaccine licensed by Merck, a prime-boost vaccine regimen from Johnson & Johnson, and monoclonal antibody treatments from Mapp Biopharmaceutical and Regeneron Pharmaceuticals.

The $170.2 million in Project BioShield funds covers late-stage development and buys up to 1.13 million vaccine regimens and an unspecified number of treatment courses of the two drugs.

Ebola is considered a potential bioterror threat, as well as a naturally occurring public health threat, underscored by the 2014-16 outbreak in West Africa that sickened more than 28,000 people and led to more than 11,000 deaths.

Funding clears way
Project BioShield, passed by Congress in 2004 in the wake of the 2001 terrorist attacks, is designed to acquire medical countermeasures to biological, chemical, radiological, and nuclear agents. The funding was set to expire in 2013, but it was extended through 2018 via the 2013 Pandemic and All-Hazards Preparedness Reauthorization Act.

Rick Bright, PhD, director of the HHS' Biomedical Advanced Research and Development Authority (BARDA), said in a Sep 29 HHS statement that 3 years ago there were very few Ebola products, even in early-stage development, and now federal officials are poised to add four Ebola countermeasures to the SNS. "We reached this point at unprecedented speed, and that's a direct result of innovative approaches to product development and to partnering across the US government, other nations, and private industry."

BARDA's funding through Project BioShield will help companies validate their manufacturing processes and take final steps to apply for Food and Drug Administration (FDA) approval. During those activities, BARDA can purchase the vaccines and drugs for potential use in a public health emergency.

Two different vaccine strategies
BARDA said it would provide $39.2 million for Merck's single-dose VSV-EBOV vaccine, which was developed by the Public Health Agency of Canada with support from the National Institute of Allergy and Infectious Diseases and initially licensed by NewLink Genetics. The vaccine is furthest along in clinical trials, showed good effectiveness in a phase 3 clinical trial in West Africa, and has been used in ring vaccination strategies in the outbreak region.

Global health officials have said multiple vaccine strategies will likely be needed to battle Ebola outbreaks, such as ones that provide quick immunity and can be used to help tamp down outbreaks, and others that offer more long-lasting immunity and could be used to protect health workers or people who live in areas where the disease is endemic.

The second vaccine to receive Project BioShield funding is Johnson & Johnson's prime-boost regimen, which is slated to receive $44.7 million. The vaccine from Johnson & Johnson, part of Janssen Vaccines, involves a priming dose of the Ad26.ZEBOV and a booster dose of Bavarian Nordic's MVA-BN-Filo.

Several vaccine trials are under way in Europe, the United States, and Africa.

Monoclonal antibody cocktail drugs
The funding also includes $45.9 million for the drug ZMapp, made by Mapp Biopharmaceutical. The drug, a cocktail of three monoclonal antibodies, was used experimentally during the outbreak to treat some patients and continues to be available for expanded access protocols in the United States and West Africa.

The second drug—which received $40.4 million in initial funding—is another cocktail of three monoclonal antibodies, REGN3470-3471-3479, made by Regeneron Pharmaceuticals. It is made using specialized Chinese hamster ovary cells with the company's proprietary technology that is designed to quickly develop a candidate drug and quickly scale-up manufacturing.

In its own news release today, Regeneron also announced a new collaboration with BARDA to develop a portfolio of antibody treatment targeting 10 pathogens, starting with influenza.

How PlantForm is using tobacco plants to develop an Covid 19 and Ebola Vaccine Tobacco, a plant notorious for triggering health problems, is now helping to fight and even prevent the spread of the Ebola virus. That’s right, tobacco plants have joined the international fight against the deadly epidemic that has significantly affected parts of West Africa. Canadian biotech company PlantForm has developed a plant-based manufacturing platform that produces low-cost antibodies, protein drugs and vaccines for as little as one-tenth of the manufacturing cost of other biopharmaceutal production systems. The company has recently begun applying its process to harvesting the power of tobacco plants to produce drugs that could prevent the spread of the Ebola virus.

There are currently five known strains or species of the virus. The Ontario-based company is concentrating on developing a drug to fight a Sudanese strain of Ebola that could potentially cause new outbreaks.

It might be surprising to learn that the concept of tobacco plant–based drugs is not new. Similar technology has been used in the past, developing drugs to treat HIV and cancer. By using techniques developed in state-of-the-art research facilities at the University of Guelph, PlantForm is producing vaccines derived from antibodies present in tobacco plants. These tobacco plants can be used to produce antibody treatments.

Here’s a rundown of the process.

Tobacco plants are grown for five to six weeks and then immersed briefly in a solution of agrobacterium bacteria, which contains the genes for the target drug.
The plants are then grown for an additional week, which enables them to produce the desired antibody in each cell.
The plants are harvested and ground up.
The antibody drug is extracted and purified, and is then packaged into vials, resulting in an injectable drug.
There are an estimated 120 biologic drugs on the market today and hundreds more in development. The global market for biopharmaceuticals is growing as more and more companies realize the advantages of biotech, and it is expected to reach $239 billion by 2015. PlantForm’s technology provides several advantages over other drug production methods such as mammalian cell culture or fermentation systems. The process speeds up development and is capable of reducing manufacturing costs by 90%.

PlantForm was one of the winners at MaRS HealthKick 2014, Canada’s largest health venture showcase. MaRS HealthKick 2015 is now accepting venture applications for its business pitch competition, including in the Biotechnology and Pharmaceuticals category. Visit the MaRS HealthKick website to learn more about the event and application process. Applications are due November 24, 2014.

First human efficacy study of a plant-derived influenza vaccine In The Lancet, Brian Ward and colleagues report two efficacy studies that are, to the best of my knowledge, the first randomised phase 3 trials of a plant-derived quadrivalent influenza vaccine.1 The vaccine material was generated in Nicotiana benthamiana, a relative of the tobacco plant. The plants were transfected with an attenuated plant viral vector (Agrobacterium tumefaciens) expressing influenza haemagglutinin genes and the vaccine was recovered from the transfected plants in the form of virus-like particles.
The first study was a placebo-controlled randomised trial with 10 160 adults (aged 18–64 years), done in the 2017–18 northern hemisphere influenza season. 10 136 participants (4051 [40·0%] men and 6085 [60·0%] women; mean age 44·6 years [SD 13·72]) received their assigned vaccine and were included in the analyses. The plant-derived vaccine was immunogenic, but only the H3N2 component induced a greater than four-fold change in the haemagglutination inhibition titre. The absolute vaccine efficacy for prevention of respiratory illness caused by vaccine-matched strains was 35·1% (95% CI 17·9–48·7), meaning the study did not meet its primary endpoint (70% efficacy). By comparison, the influenza vaccine efficacy for the 2017–18 season was 15%2 in the UK, with very low efficacy for H3N2, which was the major circulating strain.
The second study was a non-inferiority study comparing the plant-derived vaccine with a chicken egg-derived quadrivalent inactivated vaccine. It was done in 12 794 older adults (aged ≥65 years) in the 2018–19 northern hemisphere influenza season. 12 718 participants (5605 [44·1%] men and 7113 [55·9%] women; mean age 72·2 years [SD 5·7]) received their assigned vaccine and were included in the analyses. The plant-derived vaccine had an 8·8% (95% CI −16·7 to 28·7) relative vaccine efficacy for prevention of influenza-like illness compared with the comparator; though the absolute vaccine efficacy for either vaccine was not reported. Notably, although the plant-derived vaccine was equally protective, it induced a lower antibody response, measured by haemagglutination inhibition and microneutralisation.
Why is there a need for a new influenza vaccine manufactured in plants? One problem is a mismatch between vaccine and circulating strains of influenza, particularly for H3N2 strains. Circulating H3N2 viruses have become increasingly humanised (better adapted to infect human cells), which becomes an issue when the virus for the vaccine is grown in embryonated chicken eggs. During cultivation of the virus in eggs, it can adapt to attach better to the cell receptors on chicken cells, subtly shifting the sequence of the haemagglutinin antigen used for entry. Thus, the egg-derived haemagglutinin can be different to the haemagglutinin expressed by circulating H3N2 virus and antibodies raised against the vaccine strain are less able to neutralise the virus. Alternative manufacturing processes might circumvent problems of antigen mismatch caused by growth in eggs. Two alternative approaches have been licensed to date: using insect cells to make a recombinant protein (Flublok; Protein Sciences–Sanofi) and mammalian cell lines to grow virus (Flucelvax; Sequirus). The effect of changing the influenza vaccine manufacturing platform on efficacy is variable. In one study, the recombinant-based vaccine was reported to have better efficacy than a cell-derived vaccine,3 but in another study no difference was seen.4 The absence of a difference in the second study was potentially because the seed virus was initially cultured in eggs, so mutations might have occurred before cell culture expansion.5
Alternative vaccine manufacturing processes might also be important during an influenza pandemic. Many of the potentially pandemic strains of influenza come from birds, which could have a significant effect on the production of a vaccine: if the hens required to lay the eggs are infected there might be fewer eggs or if the virus is lethal in chicken embryos it might affect how much antigen can be generated. Platforms that do not require eggs might be more resistant to these problems. One issue with the use of plants for pandemics is the speed at which material can be generated, both generating the Agrobacterium vector and then growing enough plants to transfect. However, these barriers can be overcome, and the use of a plant-derived pandemic vaccine is being investigated: Medicago, the funder of Ward and colleagues' studies described here, is conducting a phase 1 trial of a plant-derived virus-like particle vaccine for COVID-19 (NCT04450004).
The field of plant-derived vaccines has grown a lot in the past 28 years, since it was first shown that viral proteins could be expressed in plants.6 There is one licensed plant-derived human therapeutic for Gaucher's disease, but this is the first time a plant vaccine has been tested in a clinical trial. It is a milestone for this technology and sows the seeds for other plant-based vaccines and therapeutics.

The history of vaccines and how they’re developed
Developing a vaccine for SARS-CoV-2, the virus that causes COVID-19, has turned into a race, and many of us are anticipating the day immunization against this infectious disease can begin.

Some may feel the creation of several potential vaccines has happened too quickly and they question whether that’s good or bad.

Sandy Salverson, PharmD, vice president of Pharmacy Operations at OSF HealthCare, said the difference in developing a vaccine during a pandemic is just about how much disease is present in our communities vs. developing a vaccine during a time when the spread of the disease is less prevalent.

“The reason the studying of the potential vaccine can happen faster is because there is more opportunity to test it,” she said. “And second, the science surrounding this particular vaccine process just continues to advance. Timelines are shortening because of the evolution of science.”

On the fast track
The U.S. Food and Drug Administration (FDA) has a fast track process designed to make it easier to develop and faster to review potential drugs, such as a COVID-19 vaccine, to treat serious conditions and fill an unmet medical need.

It’s about getting important and necessary drugs to the public earlier. Fast track does not mean cutting corners or skipping over clinical trials or the study and review of results. Fast track – in the case of COVID-19 vaccines under development – is all about the intense focus being given to create a drug that is in great need worldwide.

“Once a drug receives fast track designation, early and frequent communication between the FDA and a drug company is encouraged throughout the entire development and review process,” according to the FDA. “The frequency of communication assures that questions and issues are resolved quickly, often leading to earlier drug approval and access by the public.”

In the beginning
depiction of a historical vaccination from an 18th century Russian biology textbookVaccine development started more than two centuries ago when English doctor Edward Jenner treated a young boy by injecting him with pus from cowpox blisters found on a milkmaid’s hands.

Cowpox contains the vaccinia virus, which causes smallpox. The injection immunized the boy against smallpox. The name of the virus was used to coin the term “vaccine.”

Eradicating a disease
While smallpox was targeted by the first vaccine developed nearly 225 years ago, it wasn’t until 1980 that the World Health Assembly, following decades of efforts by the World Health Organization (WHO), declared smallpox eradicated.

To date, smallpox is the only infectious disease to be eradicated worldwide. The disease once killed up to 35% of its victims and left others scarred or blind.

According to WHO, when a disease stops circulating in a region, it’s considered eliminated in that region. For example, polio was eliminated in the United States by 1979 after widespread vaccination efforts.

Only when a disease is eliminated worldwide is it considered eradicated.

Forgotten diseases
There are 14 infectious diseases, according to the Centers for Disease Control and Prevention (CDC) that once were prevalent in the U.S. before the development of vaccines for each of them.

Those diseases include polio, tetanus, flu, hepatitis B, hepatitis A, rubella, Hib, measles, whooping cough, pneumococcal, rotavirus, mumps, chickenpox and diphtheria.

While the diseases still exist, they are no longer the threat they once were as vaccines have immunized the majority of people.

Developing a vaccine
The path researchers must take with a potential vaccine is clearly defined and overseen by the FDA. Once researchers create a potential vaccine, the producer must apply with the FDA describing the product, the manufacturing process and its effectiveness in animal testing.

From there, the vaccine begins a series of three clinical trials laid out in phases. The manufacturer must successfully complete all the phases.

Phase I: This evaluates the vaccine’s safety and ability to generate an immune system response in a small group of people.
Phase II: This tests many people, possibly hundreds, to determine the right dosage levels.
Phase III: This tests thousands of people to analyze the safety and effectiveness of the drug.
Once the results of the clinical trials are available and before a vaccine can be released to the public, there are a number of reviews and regulatory approvals for efficacy, safety and manufacturing.

Close monitoring continues once the vaccine is released to detect any unexpected adverse side effects and to further assess effectiveness among large numbers of people.

Production of a vaccine
a timeline of the history of vaccine development over the centuries infographic
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Conventional vaccines are made using viruses and can take years to successfully create due to the process of collecting the viruses and adapting them in the lab. Each new conventional vaccine requires a custom production process, including complex purification and testing.

Other vaccines use genetic code rather than part of the virus itself with a technique using messenger RNA (mRNA).

The genetic recipe is made from a DNA template in the lab. The DNA can be synthesized from an electronic sequence that can be sent across the world instantly by computer. It takes about a week to generate an experimental batch of an mRNA vaccine.

The genetic recipe directs cells to make pieces of the spikes that sit atop the coronavirus. Once it’s injected, the body’s immune system makes antibodies that recognize these spikes. If a vaccinated person is later exposed to the coronavirus, those antibodies stand ready to attack the virus.

What’s next?
We believe in the science, efficacy and safety of vaccines. Also, we continue wearing masks, washing our hands and maintaining physical distance around others until there is widespread availability of a vaccine.

“As an overarching principle, OSF is supportive of the use of vaccines,” Salverson said. “We believe they help prevent illnesses and keep our communities healthy. We are going to evaluate the safety and efficacy of any COVID-19 vaccine just like we do with any other vaccine.”

Disease prevention through vaccination is considered to be the greatest contribution to public health over the past century. Every year more than 100 million children are vaccinated with the standard World Health Organization (WHO)-recommended vaccines including hepatitis B (HepB). HepB is the most serious type of liver infection caused by the hepatitis B virus (HBV), however, it can be prevented by currently available recombinant vaccine, which has an excellent record of safety and effectiveness. To date, recombinant vaccines are produced in many systems of bacteria, yeast, insect, and mammalian and plant cells. Among these platforms, the use of plant cells has received considerable attention in terms of intrinsic safety, scalability, and appropriate modification of target proteins. Research groups worldwide have attempted to develop more efficacious plant-derived vaccines for over 30 diseases, most frequently HepB and influenza. More inspiring, approximately 12 plant-made antigens have already been tested in clinical trials, with successful outcomes. In this study, the latest information from the last 10 years on plant-derived antigens, especially hepatitis B surface antigen, approaches are reviewed and breakthroughs regarding the weak points are also discussed.