How plant-based vaccines can revolutionize the fight against infectious disease

After its refrigerator broke down in 2019, a small medical clinic in Gampela, Burkina Faso, was left with myriad ineffective vaccines against yellow fever, tetanus and tuberculosis. When the COVID-19 pandemic hit, workers at the clinic were forced to make 40-minute trips to fetch vaccines from a neighbouring clinic in Ouagadougou.

For Adama Tapsoba, a single mother of two who visits the Gampela clinic, the lack of cold storage for vaccines presents a serious problem. Tapsoba already spends four hours walking to the Gampela clinic to immunize her children. If the Gampela clinic cannot supply proper vaccines, it will become infeasible for Tapsoba to provide the health care her young children need.

For underdeveloped countries like Burkina Faso, the cold storage of vaccines is an obstacle to achieving global health equity. mRNA COVID-19 vaccines need to be kept and transported at temperatures as low as -70 C; often, resource-constrained countries do not have adequate resources or technology to fulfill this cold-chain need. Even the need for consistent refrigeration common for many vaccines is often a stretch.

Fortunately, plant-based vaccines provide a novel solution. Stable at ambient temperatures, they don’t need the expensive, logistical challenge common to most vaccines. In the future, they may also be ingested orally, which would eliminate the stigma of injections, pain and needle phobia, and the costs associated with training health-care personnel.

Plant-based vaccines are genetically modified plant lines expressing inactivated viral proteins. In plant-based vaccines, abundantly found organelles, such as chloroplasts and mitochondria, store the inactivated viral proteins, protecting them from degradation in the cytoplasm of plant cells. In essence, chloroplasts and mitochondria function as “refrigerators” of the viral proteins.

Chloroplasts and mitochondria function as “refrigerators” of the viral proteins.

Considering that -70 C temperature refrigerators cost anywhere between $10,000 to $20,000 each, plants provide an inexpensive alternative to storing vaccines.

Plant-based vaccines also optimize vaccine development by serving as a platform for scalable production. Every plant cell has hundreds of chloroplasts and mitochondria. Each organelle could store viral proteins, meaning that a single plant would function as its own vaccine development factory. Additionally, simply breeding the plants with each other would produce new vaccine-storing plants.

Another important benefit of plant-based vaccines is their mode of delivery. Currently, researchers are working to develop edible plant-based vaccines, which would lead the shift toward needleless vaccine delivery. The U.S. Centres for Disease Control reports that two in three children and one in four adults have a fear of needles – trypanophobia – and that one in 10 people will delay or not get vaccinated for COVID-19 altogether because of this fear. Trypanophobia is a specific anxiety disorder for which psychologists have struggled to develop effective treatment strategies. Exposure therapy has shown some success in treating trypanophobia, but it is time-consuming to train health-care providers and ultimately slows primary-care workflows.

The concept of plant-based vaccines was first introduced 30 years ago, and in 1998 the National Institute of Allergy and Infectious Diseases (NIAID) stated that edible vaccines would induce significant immunogenicity by using plants as bioreactors. However, to date, there is only one licensed plant-based vaccine: a Newcastle Disease vaccine for poultry in the U.S.

Until this year, no plant-based vaccine had been approved for human use. Despite the historical regulatory failure of plant-based vaccines, Medicago, a Quebec-based biopharmaceutical company, in partnership with GlaxoSmithKline, has recently developed an injectable COVID-19 plant-based vaccine (CoVLP+AS03) with comparable efficacy rates to current mRNA vaccines. In February, Health Canada approved CoVLP+AS03 for adults aged 18 to 64.

Medicago conducted a multinational, placebo-controlled randomized Phase 3 clinical trial of more than 24,000 participants and two months ago, published results in the New England Journal of Medicine, reporting a 69.5 per cent efficacy against any symptomatic COVID-19 caused by five variants (Alpha, Gamma, Delta, Lambda, Mu).

As mRNA vaccines report efficacies above 90 per cent, it may seem as if Medicago’s plant-based vaccine is less effective. However, it is important to note that the efficacy figures of the Moderna and Pfizer vaccines are associated with the original COVID-19 strain. CoVLP+AS03 was also manufactured in response to this original strain but the clinical trial results report efficacy in response to multiple COVID-19 variants. Studies have shown that the original mRNA vaccines are markedly less effective at preventing infection from these COVID-19 variants. For instance, a recent meta-analysis of mRNA vaccines against the Delta variant reported an efficacy rate of 77.7 per cent. Future studies should analyze the efficacy of mRNA vaccines against other emerging COVID-19 variants to properly compare mRNA vaccines and CoVLP+AS03.

The current barrier to the widespread use of plant-based vaccines is the lack of recognition.

Despite the efficacy and safety of CoVLP+AS03, it remains approved only in Canada. The current barrier to the widespread use of plant-based vaccines is the lack of recognition. The U.S. Food and Drug Administration (FDA), for example, does not have a regulatory process for plant-based vaccines yet because it classifies them as genetically modified crops. Additionally, plant-based vaccines are still a relatively novel concept, and skeptics say more research is required before plant-based vaccines can hit the market.

Even in Canada, only 580 doses of CoVLP+AS03 have been administered. The low uptake is due to the fact that more than 80 per cent of the Canadian population was already vaccinated for COVID-19 with two doses at the time of approval of CoVLP+AS03. The Canadian government invested $173 million in the development of CoVLP+AS03 in hopes of fulfilling its goal of donating 200 million vaccines through the vaccine-sharing program COVAX. Unfortunately, the World Health Organization, a governing body of the COVAX program, has rejected Medicago’s plant-based vaccine because of company ties to the tobacco giant Philip Morris, which holds a one-third stake in Medicago.

Plant-based vaccines show tremendous potential in fighting COVID-19 and future pandemics. However, for these drugs to gain traction, some prerequisites must be fulfilled. First and foremost, the FDA must re-classify plant-based vaccines and devise a unique evaluation process for these drugs. This will legitimize the concept of plant bioreactors for pharmaceutical development and pave the way for university research laboratories and private biotechnology companies to pursue these ideas. A proper regulatory framework should integrate the current approval processes for genetically modified crops and vaccines. The development of this protocol for approving plant-based vaccines may already be underway as Medicago has recently initiated the regulatory filing process with the FDA.

Additionally, further research must be conducted into molecular farming and plant biotechnology to ultimately improve vaccine efficacy rates and limit adverse side effects. Special emphasis must be placed on improving antigen selection and managing dosage consistency.

For Adama Tapsoba and so many others, regulatory approval of plant-based vaccines may mean accessible health care for generations to come. Eliminating the need for the expensive vaccine cold chain and outdated needle delivery would represent a major leap in achieving global health equity.