A Plant-Based COVID Vaccine: Which Patients Would Benefit?

Véronique Duqueroy

May 26, 2022

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The first plant-based COVID vaccine ever produced was approved on February 24 in Canada for adults aged 18 to 64 years. Covifenz, manufactured by Medicago, is to be administered in two intramuscular doses on day 0 and day 21.

The originality of this new vaccine lies in its use of recombinant spike particles produced from a close relative of the tobacco plant (Nicotiana benthamiana). According to Health Canada, it is recommended in Quebec only "for people with a contraindication to administration of an mRNA vaccine or fears concerning that type of vaccine," because its vaccine efficacy is lower than that of RNA vaccines (71% vs 94.1% for the Moderna vaccine and 95% for the Pfizer vaccine). The results of the phase 3 clinical trials conducted in nearly 3000 subjects were published in May in The New England Journal of Medicine and indicate an efficacy ranging from 69.5% against symptomatic infection to 78.8% against moderate to severe disease.

At the end of March, the World Health Organization (WHO) announced that the application for approval of the Medicago vaccine was paused due to the company's ties with the tobacco industry. Quebec-based Medicago is actually not a Canadian-owned company. The Japanese group Mitsubishi Tanabe owns a 79% stake, and tobacco industry giant Philip Morris holds a 21% stake. The WHO's decision to pause the approval process for Covifenz reportedly is not related to the safety and efficacy of the vaccine. "WHO and the United Nations have a very strict policy regarding engagement with the tobacco and arms industries," stated Mariângela Simão, MD, WHO assistant general director.

Beyond the ethical or lobbying aspects, this plant-based COVID vaccine constitutes a first and could open the door to other vaccine alternatives. We interviewed Benjamin Davido, MD, a tropical and infectious disease specialist at Raymond-Poincaré Hospital, Paris Public Hospital System, in Garches, Paris, France, who emphasized the medical advancement this vaccine represents and questioned both the media silence and the WHO's position.

Medscape: This is the first plant-based COVID vaccine. What do you think of it?

Davido: Researchers have been working for nearly 20 years on plant-based vaccines, mainly for flu, using either corn, tobacco, cotton, or potato leaves. I find the idea very appealing. Here, the principle is the cultivation and synthesis by shrubs of protein equivalents, VLPs or virus-like particles, which are kinds of decoys or copies of target proteins (in this case, the SARS-CoV-2 spike protein). What is surprising is that even though this VLP technique has been around for a long time, to date we hadn't yet had a plant-based vaccine, and then suddenly we're there! It may not have the same vaccine responsiveness, [but it] is easier to implement. In fact, it is now well known that the vaccine target, the spike protein, is very immunogenic, and it may be that previously, the targets of the so-called "conventional" flu vaccines had not been good candidates for this type of vaccination. In any case, no one's been talking about it.

I am also amazed, positively so, that this was the subject of a publication in The New England Journal of Medicine.

Also, it is one of the rare studies on vaccines that deal with the effect of variants on vaccine efficacy. To my knowledge, there had not been anything published on this subject for several months, so it's an original article. We see that the vaccine was tested based on the original strain, as well as Alpha, Beta, Gamma, Delta, Lambda, et cetera. I didn't really understand why they separated Mu from Omicron, because I consider it to be the same thing. The moot point is that at the time of the study, they obviously didn't have the Omicron variant and very little of the Mu strain. In contrast, there were lots of Delta variants and, once again, there were very few vaccines that tested Delta so exhaustively.

Medscape: What are the limitations of this vaccine, in your opinion?

Davido: There are certainly some negative aspects. First of all, if you compare it to other vaccines, the global efficacy is 70%, which I consider to be disappointing. From what I recall, Novavax, another mRNA alternative, has a global efficacy of about 90%. So, it definitely falls short. Additionally, there is no indication for individuals over [age] 65 [years], because there is a lack of study power, with a very wide confidence interval [–3300 to 97], which is obviously very troublesome for a vaccine, especially since we know that currently the vaccines, and especially the boosters, are indicated for individuals with comorbidities and thus elderly individuals. The fact that there was no arm studying the use of this vaccine as a booster can be criticized, but this is true of many other vaccines, so the criticism is entirely debatable.

Medscape: How is it positioned in relation to other non-RNA COVID vaccines?

Davido: Covifenz has an efficacy of 78% against severe forms; Novavax has an efficacy of 100%. This 100% figure can be disputed, but 78% is definitely lower. However, as with Novavax, with Covifenz we have the prospect of a second vaccine that is positioned as an alternative to the mRNA vaccine, which is welcome knowing the mistrust of some individuals, and it paradoxically reinforces the merits of mRNA vaccines in view of their unparalleled potency.

Furthermore, Novavax and Covifenz both use an adjuvant, precisely because they are not very effective. I refer you to the earlier controversy regarding COVID vaccination and, in particular, 10 years ago with the H1N1 vaccine, where people and even some scientists were shocked by the idea of vaccination adjuvanted with squalene. I would point out that this is one of the reasons that flu vaccines are no longer adjuvanted today. Novavax is a protein-based vaccine adjuvanted with Matrix-M, which is a wood extract from Panama, whereas Covifenz contains a squalene-based adjuvant (like the H1N1 vaccine). It's quite ironic because some people demanded an alternative to the mRNA vaccine and, actually, we find that the alternative to the mRNA vaccine often is a vaccine containing an adjuvant, although adjuvants have not been associated with more adverse effects.

Medscape: What proportion of people are unable to receive an mRNA vaccine?

Davido: Among my patients, I have very few. I have only had two patients in the past 6 months who challenged me regarding getting non-RNA vaccines and for whom I proposed Novavax (but they still aren't vaccinated).

I think that there is strength in numbers; it's good to have two [options]. But there is very little to be gained in choosing the mechanism of action over efficacy. Also, we will have to develop single-dose vaccines if we want to democratize vaccination.

Medscape: What do you think of the WHO decision to reject Covifenz because of its links to the tobacco industry?

Davido: Pharmaceutical lobbying has received a lot of criticism, and in this case it is lobbying by the tobacco industry that is being denounced. But if tomorrow Philip Morris were to use its tobacco plants to produce vaccines rather than manufacturing cigarettes, this would instead be good news, wouldn't it? I don't understand the WHO's unfavorable opinion.

What is amusing is that this vaccine could be indicated for people who don't want to get mRNA vaccines for ideological reasons. Moreover, it is a vaccine that could be considered "eco-friendly" because it is plant based, which runs counter to the usual argument against vaccines, et cetera.

But I don't understand why there isn't more discussion of these results, which, again, were published in a major journal like The New England Journal of Medicine. This seems a bit like scientific censorship, which isn't right, because it is the best answer to those who accused us of manufacturing vaccines for the pharmaceutical industry. Watch this space.

This article was translated from the Medscape French edition.

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