A post in collaboration with The Shared Microscope
Caution: Smoking tobacco is harmful to health, and as most of you know, is carcinogenic. This article in no way encourages to use of tobacco as protection against COVID-19.
In response to the COVID-19 pandemic, several drug companies, including AstraZeneca, Moderna, Pfizer, Johnson & Johnson, Sinovac, and Novavax, have successfully created vaccines that are currently being deployed to individuals worldwide. Medicago and GSK have also joined forces to develop a unique vaccine against COVID-19.
Medicago, a biopharmaceutical company headquartered in Canada, focuses on developing plant-based therapeutics in response to global health challenges, COVID-19 being no exception. In response to the pandemic, Medicago (alongside GSK) developed a COVID-19 vaccine unique to all the other vaccines recently developed against COVID-19. So what's special about the vaccine? Interestingly, this is the first COVID-19 vaccine that is entirely plant-based. Yep, you heard that right — made in plants! Tobacco plants (ish)!
What plant is the Medicago COVID-19 vaccine made in?
Medicago's vaccine is made from a close relative of the tobacco plant, Nicotiana benthamiana. Ironically, tobacco has plagued humans with lung conditions ranging from COPD to lung cancer for decades. Surprisingly, this notorious plant has been critical in manufacturing vaccines against COVID-19-related pneumonia in the past year.
Plant-based vaccines are cheap to produce, safe, and rapid for developing vaccine ingredients such as the Coronavirus-like particles. Plant-based vaccines are also highly scalable and provide manufacturers with increased flexibility. As highlighted by the peer-reviewed paper linked here, the Nicotiana benthamiana is the core production host for various companies aiming to further human medicine, including Medicago, Icon Genetics, iBio, and Lead Expression Systems.
Nicotiana benthamiana is often the production host of choice because it has a defective plant immune system, making it easy to produce new vaccine ingredients. Research suggests that the plant sacrificed its defensive system in favor of a hastened reproduction cycle. A strategy that enabled the plant to cope with severe drought weather in central Australia. This susceptibility to infection enables the plant to quickly undergo genetic transformations and transient gene expression, making it an excellent mini-factory for protein production.
How are plants used in vaccine development?
For over a decade, Medicago has been developing a technology that harnesses the power of plants to develop vaccines. More specifically, using a bacterium, the plant is "fed" information about a virus to produce the main ingredient of a vaccine (also known as the active ingredient).
The plant is programmed to produce the vaccine -- to do this, Medicago only needs the virus's genetic sequence rather than the virus itself. The genes are then introduced to the plant via a bacterium. The plant's normal machinery will produce the vaccine ingredient against the virus through a natural process within the tobacco plant. The plant can produce the vaccine's active ingredient in approximately one week from the date of initial exposure to the pathogen. The active ingredient is then harvested and purified for use in a vaccine candidate. The vaccine candidate can then be produced within 5 to 6 weeks.
For the coronavirus vaccine in development, Medicago focuses on producing Coronavirus-Like Particles that mimic the virus's structure. Please note: although the Coronavirus-Like Particles are structurally identical to the SARS-CoV-2 virus (which causes COVID-19), they do not contain any of the genetic material of the virus, and therefore, are unable to cause infection.
To learn more about the COVID-19 vaccine in development by Medicago, feel free to check out the following video:
However, the production of the vaccine candidate is only half the battle won: the vaccine candidate then has to pass various safety and efficacy tests before the vaccine can be commercialized for use in humans. This testing process is further explained in an article linked here.
Tell me more about the Coronavirus-Like Particle Technology
Virus-like particles, such as the coronavirus-like particles manufactured by Medicago, are structurally identical to wild-type viruses. However, they lack the genetic material inside the virus. Because of this, the virus-like particles are unable to replicate or cause infection in the vaccinated individual.
Below is an image of Medicago’s CoVLP compared to an image of a wild-type SARS-CoV-2 virus:
It can be argued that vaccines produced in plants are faster and more accurate because no manipulation of the virus is required. The vaccine development also does not require that viruses be handled in the laboratory. Research so far suggests that virus-like particles have had an equivalent or superior immune response in mice when compared with live viruses.
Virus-like particles cannot develop any mutations and are also structurally stable, unlike mutations that may sometimes develop from traditional vaccine manufacturing. The virus-like particles can elicit an immune response via antigen-presenting cells (a type of white blood cell) found in the human body, leading to a robust immune response in the vaccinated individual.
The virus-like particles fool the immune system to protect an individual from disease. Virus-like particles look like the disease-causing virus that can trick the immune system into making antibodies that will protect against the actual infectious pathogen if naturally exposed to it.
Isn't Medicago working with GSK for this vaccine?
Yes, Medicago has joined hands with GSK for the development of their COVID-19 vaccine. As part of the partnership, Medicago manufactures the active ingredient to be used in the vaccine. GSK provides its pandemic vaccine adjuvant system for the same.
What is the importance of the adjuvant? The adjuvant plays a vital role in the pandemic and has done so amid the last flu pandemic of 2009. The pandemic adjuvant reduces the amount of vaccine protein required per dose, allowing more vaccine doses to be produced overall. In other words, the Medicago vaccine can be “diluted” using the Medicago pandemic adjuvant, which can help to protect more people overall. This “dilution” using the adjuvant enhances the immune response and provides long-lasting immunity against infection.
Is the Medicago vaccine vegan?
This seems like an apt question here. Is the Medicago COVID-19 vaccine really vegan? Medicago has not directly responded to this question (yet). But one thing is clear, the active ingredient of the vaccine, the coronavirus-like particle, is not of animal origin. More information is required about all the other ingredients used in the vaccine before we can certainly comment about whether or not the vaccine is vegan.
What's the current situation?
The Candian company, alongside GSK and Philip Morris, recently reported promising results from their Phase I and II clinical trials. The vaccine is now in the final phase of human trials. To learn more about the vaccine development process, feel free to check out this article here.
Depending on the results of the Phase III trials, the company has reached an agreement with the Canadian government to accelerate its COVID-19 vaccine candidate efforts. The government has agreed with the company to supply 76 million doses of its COVID-19 vaccine within Canada.
Carpe Fiscus! The time is ripe to stimulate the "pathway to independence" for early career researchers.
In August 2017, faced with the increasing probability of drastic budget cuts under the Trump administration, the NSF Directorate of Biological Sciences announced it would no longer be funding its long-praised Doctoral Dissertation Improvement Grants (DDIGs). This decision marked a turning point in funding opportunities for graduate students, who are particularly vulnerable to a lack of grant options. As a graduate student at the time, I wrote about the decision and its ramifications for myself and my peers, citing the NSF's choice to slash the program as a brand of "trickle-down" academics. I noted that the decision to cut DDIGs was worrisome for early-career researchers, heralding a further consolidation of academic power at the very top levels of the hierarchy and diminishing agency for already-vulnerable trainees.
Just under four years later, the world and I have both moved on – I passed my dissertation defense and began a new chapter in my academic training. The US handed the reins of power over to a markedly different administration, one constantly challenged by the lingering watermarks of its inherently anti-science predecessors. With this country-wide transition and the eyes of the world increasingly on academic research during a global pandemic, we sit at the cusp of an incredible opportunity to push funding opportunities for early-career researchers further than ever before.
Funding for Early Career Researchers
Most graduate students in STEM are funded through a combination of research and teaching assistantships, the money for which comes from grant and institutional funding, respectively. Grant funds are often awarded directly to the student's principal investigator or PI — the person directly responsible for mentoring and supervising graduate students. Teaching assistantships are often seen as less desirable by the students and their PIs, as teaching takes time away from research. Therefore, research assistantships are prized but depend entirely on the PI for funding and tend to be fairly restricted in subject matter. The PI faces pressure to publish and present on the experiments laid out in the original proposal as this evidence of success is instrumental in future funding decisions; there is usually little room for creativity or independence from the grad student.
Funding opportunities for postdoctoral fellows are often similarly awarded to the PI rather than the fellows themselves, with fairly rare exceptions. The NSF has a single program aimed solely at biology postdoctoral fellows called the postdoctoral research fellowship in biology (or the PRFB), while the NIH, the other major funder of foundational research in the US, has several opportunities geared directly at postdocs, including their F32, K25, and K99/R00 awards. Competition for these awards is fierce. It is much more common for postdocs to be funded as a component of grants awarded to established PIs, leaving little opportunity for postdocs to control the direction of their research. Instead, they remain bound to research that can directly tie into the goals of the grant they are funded under – goals which they may have had no hand in setting.
Rightly or wrongly (and it would be the topic of a whole other post to unpack whether it's right or wrong), we predominantly train our graduate students and postdocs to be future PIs. PIs must be able to independently find funding opportunities, generate innovative research proposals, and follow through on those proposals' aims. These steps all involve thinking creatively, responding to unpredictable events, and adjusting accordingly. While funding decisions are based strongly on publication record, they also depend heavily on a proven track record of securing independent funding. Depriving our early-career trainees of opportunities to establish a funding track record makes their professional and academic journeys much harder. It takes away their agency, leaving them more reliant on their PI.
Hopefully, if you've read this far and are still invested in reading further, I've convinced you that funding opportunities for early-career researchers should be expanded. What can we all do to make sure that this expansion happens? Well, the answer will likely depend on who you are and your specific role within publicly-funded research.
For fellow academics, especially those further along in their careers: