Plant-derived COVID-19 vaccine candidate starts rolling review with Health Canada
The tech – which the company has honed over years with its influenza vaccine candidate – uses plants to produce protein particles for the vaccine. If authorized, the COVID-19 vaccine will become the company's first commercial product.
Plants as 'mini protein factories’
Founded in 1999, Quebec City’s Medicago is a pioneer of plant-derived therapeutics.
Its tech takes the idea of traditional vaccine manufacturing – based on using eggs to produce viruses – and instead uses living plants as the bioreactor that produces a protein particle that mimics the target virus.
The first step is to create the required protein particle and introduce it into a plant-specific bacterial vector. This is then taken up by plants which multiplies the vector. It takes just four to six days for the ‘mini-factories’ to produce the Virus-Like-Particles (VLPs) – compared to around six months for egg-based production (The company highlights that plants are not genetically modified; rather, the plants’ natural cellular processes are used).
While initial experiments had used alfalfa (Medicago is the Latin word for alfalfa), today the company uses N. benthamiana plants: a relative of tobacco which has a weakened immune system meaning genetic material can be hosted rather than rejected by the plant.
'Unleash the power of plants!'
Up to last year, the company’s frontrunner had been its influenza vaccine. Like a number of other biotechs, its focus shifted with the onset of the pandemic.
“Our work on our COVID-19 vaccine candidate started in February of 2020 where we were able to produce a VLP after just 20 days of having the genetic sequence,” Nathalie Landry, Medicago’s Executive Vice President, Scientific and Medical Affairs, told BioPharma-Reporter.
“As we had been working on other vaccine candidates, it was not difficult for us to pivot and apply the technology to our COVID-19 candidate.”
Medicago has already taken other plant-based candidates into large-scale clinical studies: and the lead quadrivalent VLP influenza vaccine is already under review with Health Canada.
However, the COVID-19 vaccine candidate is now in a position to overtake the influenza application and has the potential to become the company’s first commercial product.
The COVID-19 candidate uses Coronavirus-Like-Particle (CoVLP) technology with the vaccine composed of recombinant spike (S) glycoprotein expressed as virus-like-particles (VLPs) co-administered with GSK’s pandemic adjuvant. Two doses are administered 21 days apart (3.75 micrograms of CoVLP per dose).
A Phase 1 study of 180 healthy subjects aged 18-55 reported that the candidate ‘induced robust neutralizing antibody and cellular immune responses’, with antibody levels higher after vaccination than observed in convalescent sera. The vaccine was granted Fast Track designation by the US FDA in February this year.
The publication of Phase 2 data is expected shortly.
A Phase 3 trial, which started in March, is enrolling up to 30,000 participants across 11 countries, with the company expecting to finalize the data by the end of the spring. Medicago has also initiated a feasibility study to address emerging COVID-19 variants.
Health Canada has now started to assess the data under an Interim Order rolling submission: whereby Medicago submits nonclinical sections, quality and clincial safety, and efficacy information as they become available.
If the vaccine is authorized, commercial production could then be ramped up – ultimately reaching 1 billion doses a year.
“Depending on final dosage, we should be able to produce up to 80 million doses of the vaccine by the end of 2021,” said Landry.
“We will be able to potentially double this amount of doses by 2022. We are going to produce the COVID-19 vaccine doses at both of our sites in Quebec and in North Carolina.
"We also have a large scale manufacturing site under construction in Quebec, which will produce about 1 billion doses per year of pandemic vaccines when completed.”
Quebec city production site
Medicago started construction of its $245m Estimauville manufacting complex in Quebec city in 2018. The intitial plan for the 44,000m2 site was to produce 40-50 million doses of quadrivalent vaccines against seasonal influenza as of winter 2021. The facility will house 400 jobs.
However, as it noted when breaking ground on the site: "In case of a pandemic, the factory will be able to produce a vaccine in 5 to 6 weeks, compared to 5 to 6 months for traditional vaccines technologies."
Advantages of a plant-based platform
Canada has authorized four COVID-19 vaccines to date: Moderna and Pfizer/BioNTech’s mRNA vaccines; and AstraZeneca and J&J’s viral vector vaccines.
Landry says the plant-based platform, however, offers a unique candidate for a number of reasons. It is versatile, because of the platform’s ability to produce both vaccines and antibodies with the same platform. And it is easy to scale up manufacturing, because the same growing conditions are required whether there is one plant of 10,000 plants.
In the case of influenza, Landry also highlights the platform’s accuracy: able to accurately match the recommended target strains (a mismatch between vaccine and circulating strains of influenza can be a problem for traditionally produced vaccines: as mutations can be introduced in egg-based production).
The company is also exploring a number of other vaccine candidates for the plant-based platform: including an adjuvanted influenza candidate, pandemic flu candidate and rotavirus candidate. And then there is also the potential to develop the tech for therapeutic products beyond vaccines.