• Race to a Cure Authors

Expert Vaccine Update: Biodextris and Emergence Creative

Representatives from Canadian pharmaceutical company Biodextris and the CEO of Emergence Creative discuss Vaccine Reluctancy and its Effects on Vaccine Roll Out.

As of January 14, 521 648 Canadians have received a dose of either the Pfizer-BioNTech or Moderna COVID-19 vaccines. That is just over 1% of the population. It takes 70% of people to be vaccinated and immune to achieve herd immunity for the remaining 30%. Given the 94 to 95% efficacy of the current vaccines, Canada would need to vaccinate at least another 27 407 546 people to reach this level of communal immunity. However, how will we achieve that level of mass vaccination when some 60% of people are unwilling to take the vaccine? What is driving this vaccine reluctance?

To answer this question, I talked with John Mukherjee, the Director Of Marketing And Business Development at Biodextris, and Raj Pannu, the co-founder and CEO of Emergence Creative, to discuss vaccine reluctancy and its effects on vaccine rollout. Biodextris is a Canadian Laval, QC-based contract pharmaceutical development and manufacturing firm, and a BIOTECanada’s vaccine committee member. They are working with Saskatchewan’s VIDO-InterVac vaccine to manufacture part of their vaccine for early-stage human clinical trials. Emergence Creative is a global creative agency based in New York dedicated to social impact. They work to create engaging, scientific, and socially impactful solutions in global health, education, sustainability, health sciences, social enterprise, and more. Emergence Creative is exploring vaccine reluctance during this pandemic. Pannu has a broad knowledge of immunology and a Ph.D. in biochemistry.

Being at the frontiers of vaccine development and vaccine rollout, both Mukherjee and Pannu were able to break down what vaccine reluctance towards the COVID-19 vaccines entails and what it means for public health.

The following is an edited transcript of my interview with John Mukherjee of Biodextris and Raj Pannu of Emergence Creative. Some information has been edited for brevity and clarity. No unauthorized copying or reproduction of this material is permitted.

Interview with John Mukherjee and Raj Pannu

Both the Modern and Pfizer-BioNTech vaccines that are being delivered in Canada are mRNA vaccines. What are mRNA vaccines and how do they work?

Mukherjee: To understand how mRNA vaccines work, you have to understand RNA, DNA, and the human cell as a whole. The human cell comprises of several different small parts, called organelles. One such organelle is the nucleus which holds all your DNA and has its own membrane to isolate it from the rest of the cell while only letting some things pass through. When it comes time to encode a protein, certain sections of your DNA get unwound, these sections are called genes. The gene then gets read by a molecule that creates a copy of your DNA called messenger RNA or mRNA. Your DNA is staying intact safely inside the nucleus; all it is doing is creating a copy. This mRNA gets translated into a different format composed of a variety of molecules called tRNA. Then, all the tRNA molecules line up alongside their respective mRNA partners. On the back of each of the tRNA molecules is an amino acid that joins them together as complementary RNA pairs. You then get a string of peptides that become the protein, which eventually shears off, folds into the proper shape, and goes to do whatever it's supposed to do in the body. What is important to understand is that mRNA is a copy of the DNA. Our DNA is unchanged, and we are merely replicating it.

How do mRNA vaccines differ from each other and how do they compare to traditional vaccines?

Mukherjee: All mRNA vaccines work similarly; the only difference is how they traffic mRNA into the cells. Each company working on an mRNA vaccine has a different method of trying to get that information into your cells with a copy of mRNA, that has not come out of our own nucleus, but has been artificially produced and put into the cell. This artificially produced mRNA eventually gets coded into proteins, which become the antigen, then decomposed and reabsorbed into the cell. Antigens are what summon your immune system to fight the virus. The main difference between traditional vaccines and mRNA vaccines is that we are producing the immune-system alerting antigens for ourselves in mRNA vaccines. In traditional vaccines, we go through actually making those antigens—whether through a chicken egg vector system, through some sort of microbial fermentation or by cell culture—then formulating it with an adjuvant and/or other components and packaging it in an injectable format. The reason why we have seen mRNA vaccines move so quickly in response to the pandemic is because we are cutting out a substantial portion of process development. In the traditional approach, you need large amounts of starting material to produce adequate amounts of antigen. With mRNA vaccines, we need only a fraction of the amount of material, nucleic acids, and the body makes the antigens itself.

Photo by Daniel Schludi on Unsplash.

Given the urgency of the situation, are mRNA vaccines a better approach to COVID-19?

Mukherjee: Yes. We can generate smaller volumes of mRNA vaccines that are more potent to produce a grander effect with smaller dosages. Also, by taking the mRNA approach, we can shorten the time taken to develop a vaccine. A traditional vaccine, even when expedited, can take anywhere between five and ten years. Since we are skipping significant steps when we make mRNA vaccines, those vaccines come out first. The interesting part is the difference in side effects between the mRNA and traditional vaccines. According to some recent observations in the first few to be vaccinated, mRNA vaccines tend to have more pronounced side effects after injection. This makes sense because a few of your cells are being pushed to produce these antigens; this causes many local effects similar to a bacterial infection but are short-lived.

So now that we understand how this vaccine works, what makes people so reluctant to get it?

Pannu: When you look at the polling data in Canada, the number of people who answered yes to the question "If a vaccine comes onto the market, would you take this vaccine?" has been continually changing. In July 2020, only about five in ten Canadians said they would take the vaccine. Then between July and September, that number dropped to 39%. Since September, we have had many governmental approvals and data from Pfizer and Moderna saying that this new technology platform has promising efficacy rates. You would think that would increase people's confidence, but only 40% of people would take the vaccine if available to them as of late December. That number may be somewhat artificial because people tend to be cautious about something unknown, but they might take it when given the opportunity. Regardless, there will not be a massive shift in numbers. A concept called herd immunity means that if enough people have immunity to a virus, the virus cannot cause community transmission within that population because so many people are immune. This protects people who are not vaccinated since the immune people insulate them.

Is there a minimum percentage of people that need to be vaccinated to keep the entire population safe with herd immunity?

Pannu: Yes. There is a minimum number of people that need to be immune to protect the small number of people who are not, but in order to understand the numbers, you have to take vaccination rate, vaccine efficacy, and population into effect. The current vaccines in Canada are 95% effective, but only 40% of Canadians are willing to take the vaccine. To achieve herd immunity, you need about 70 to 80% of people to take the vaccine, given its efficacy rate. Given Canada’s population, that translates to 26 million people needing to be vaccinated when only 12 million people are willing to take the vaccine. We would need to convince some 14 million people who are hesitant to take the vaccine to take it.

Given the large numbers of people reluctant to the vaccine, would it be possible for the government to make vaccination mandatory?

Pannu: That is a fascinating public policy question. To what extent is the government prepared to make it mandatory for people to take vaccines? Right now, despite the horrible economic damage and the enormous loss of life, there still does not appear to be enough desire on the part of the government to force people to take it. That is of some concern.

What will it take to get vaccine reluctant people to change their minds?

Pannu: What is the root cause of the distrust? First, people are concerned about corporations, which is expected because there have been many cases of unethical business practices. In the United States, there is a high cost of health care, and people tend to be distrustful of corporations as people believe they are looking out for the corporation's economic interests, not necessarily the individual. Second, there is mistrust of governments. There is a very famous example in Alabama, USA, in the 1930s, known as the Tuskegee incident. A United States public health agency was doing clinical trials on human subjects without their knowledge and injecting people with live syphilis. That is a horrible example in public health that has created enormous distrust among African-American communities for public health agencies that still exist today. Third, there is the political dynamic of false equivalence in which there are two sides: either the economy shuts down, or everybody gets COVID-19. Both sides tend to be extremely loud and aggressive about what they think is important when in some ways, these factors are more interrelated than people may think. That is partially because from the public health side, the communications have been relatively low. There's a lack of criteria for what should be open due to the lack of precise guidance. This breeds distrust, and on top of all that, when you add this new, quickly progressing technology platform, we have this big mess that causes people to be hesitant about taking a vaccine.

Many government policies seem to be divided. During one point in the lockdown, a commercial road between Toronto and Peel was split between zones and one side of the road’s stores were open for business and the other was closed. So how are these types of situations affecting the efficacy of the lockdown measures and what can the government do about it?

Mukherjee: The problem is that the people who are leading do not have the right background. People who advise leaders do have a public health or science background but are not getting their say in what should be done. This balance between economy and safety seems always to have been considered as two sides of a spectrum when they go hand in hand. We would do a lot better if more people handled this issue with a sense of community instead of being policed by the government. There has been tremendous success in other places like China, but they are under a communist rule where they do what they are told; otherwise, they would get other ramifications or, worse, COVID-19. That governmental system has allowed China to set up their pandemic approach differently from what we are doing in democratic societies like Canada and the United States. I am not saying that is necessarily the correct way of handling a situation like this, but having a community motion in how we do things rather than artificially splitting regions up, seems to be a better approach.

How did the past SARS outbreak provide an example to the current COVID-19 response?

Pannu: SARS should have been a wake-up call in some ways. In the United States, the Obama administration looked at SARS as a near miss. They were very concerned about the possible implications for an airborne transmissible respiratory virus. Despite all the preparation done after that epidemic, I think it's disappointing that the Canadian and American governments could not do much to protect their people now. However, if you look at places like Australia, they protected their population, but at a high personal cost to the people. In the Australian state of Victoria, where Melbourne is, there was a big lockdown where everything just shut down, and people stayed home for a few weeks. It was challenging, but there was a coordinated effort with economic relief paired with a total lockdown, making people understand how serious this was. Now everything in Australia is fine, and they are almost back to normal. New Zealand is basically down to zero cases, and they can move on to other more important things. This proves that it is possible to eradicate this disease quickly. Culturally, in the United States and parts of Canada, people tend to be more individualistic and focused on personal and family needs instead of communal safety. Many transmissions are happening because people are not sufficiently afraid of this disease. They don't understand how dangerous it is and that there currently is no cure for this disease. Part of the solution is going to be to get people to take this seriously. Nevertheless, it does not appear to have happened partly due to the government's mixed messaging. It's a terrible time to be a leader because there are so many different constituencies coming to you, from small businesses to the threat of unemployment and public safety. The main goal would be for public policy to figure out how to be limber enough to keep people afloat and get rid of the disease.

Many studies are ongoing to analyze the possible circulatory, respiratory or even brain damage caused by the virus. What do you know about the long-term side effects of COVID-19?

Mukherjee: Biodextris and its partners are working on several different therapeutics, as well as COVID-19 vaccines. There are two schools of thought on how to tackle this pandemic: either get a vaccine and eradicate it from the population, which in some ways is the cheaper method, or to treat the worst symptoms that cause the most damage with various newly developed therapeutics. Both options have pros and cons. Therapeutics could be used on many viruses potentially but not eradicate the cause, the virus. Vaccines are specific to one virus and do not typically help with any other virus, but they eliminate the problem. COVID-19 has now been implicated with circulatory, respiratory, and in some cases, cerebral damage. The speculative cause is vast amounts of cellular damage and debris combined with acute inflammation, leading to widespread clotting. What is concerning is that these effects are being observed in the younger population as well. Also of concern is that immunity appears only to be temporary, ending after 3 to 4 months in some. If the data is correct, you can be hit again, and if you look at it as an erosion effect, and if you get hit the second time and you were not ready for it, the second time you hit you a lot worse. So when does it end? The cycle keeps going, and as it continues to undergo transmission from host to host, significant mutation will occur over time as well all making a negative impact on herd immunity.

Pannu: Since this disease has only been known to science for the last ten months, the natural history and how it impacts the body is mostly unknown. There is much variation in the level of symptoms: some people get strokes, deep venous thrombosis, mood-related things, depression, or different kinds of gambari and paralysis. Generally, there's a variety of different COVID-19 symptomatology and analysis of what's directly related and secondary. All disease symptoms result in cellular debris, which can impact people's liver, kidneys, and other organs. It's currently unknown, but I think science will discriminate and develop specific therapeutics for a lot of these things. However, the main problem is that you cannot game out this thing. You cannot use your rational mind and try to understand something invisible and highly contagious. There's no way to know whether the decisions that you're making are right or wrong, especially if you're going to subject yourself to risk. People tend to have a false sense of confidence that they can figure out the right or wrong thing. Being a young person and losing a year of your life is horrible, so I'm not shocked that people are making bad decisions. It's not surprising but it's unfortunate.

There is a lot of misinformation about COVID-19 and vaccines. Can you speak to that?

Pannu: The issue of misinformation is complex. It is not limited to COVID-19. We live in an era where the technology around information is so sophisticated that people can interact so quickly that information—regardless of positive or negative—travels incredibly fast. Additionally, everyone has the power to create information, and sometimes what appears to be valid is not. That is where misinformation comes in. On the vaccination front, the false links between vaccination and autism were a cause of erroneous publications, but then celebrity endorsements pushed that story out there, furthering the misinformation. There are so many different agendas and so many different constituencies around misinformation. What is interesting with COVID-19 is that we are working with an international consortium of misinformation. Misinformation comes from multiple sources, acting almost like a virus because it goes viral, mutating and changing as it goes into different areas. The sad thing about it is that, whether you live on a small island off the coast of British Columbia or in a major metropolitan city, you could be getting information from Russia, Africa, Europe, or anywhere in between. Despite the geographical distance, all that misinformation is still part of your local ecosystem. People live in information bubbles because we have our Instagram, Facebook and Twitter algorithms constantly reinforcing things that we already believe. As we consume the same type of information over and over again at high frequency, we are getting our affirmations reaffirmed back at us, creating a confirmation bias. It is a very challenging information ecosystem for anybody who is well-intentioned to inform people correctly. Like in China, strong centralized governments can mandate everything that happens and shut down some information sources but you cannot do that in democratic societies. Some well-intentioned people are doing their best and I am sure we will get through this somehow, but it is a very challenging situation.

Mukherjee: Raj hit the most critical points, but I hope people realize that you have to take the time to evaluate your sources of information and look at what the personal gain or political gain is in the statements that are being made. People need to take that extra five minutes to trace their information back to the source before sharing it to add an element of quality control to what kind of data you will let into your brain and then propagate to your friends and family. The big takeaway is to qualify your sources before believing them.

Featured image courtesy of Unsplash.

Article Author and Interviewer: Ria Patel

Article Editor: Olivia Ye