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Does Vaccination Increase Inequity?
15 Minute Read
How ironic it was that, as we sat in the gilded Coffee Room of the Cavalry & Guards’ Club, discussing arguably one of mankind’s greatest achievements, the Kremlin was poised, in the teeth of global opprobrium, to vent its demented fury on the innocent civilians of Ukraine, with all the death, destruction and human misery that would inevitably follow. We were surrounded by fine paintings reminding us of the glorious military victories of Wellington. Of course, Wellington fought for the right side, but however gloriously depicted after the event, war is always a stain on humanity.
As I was driving recently to collect my daughter from school, I had tuned in to Planet Rock on the radio (don’t worry, I am equally appreciative of the work of Tallis, Byrd and Gibbons - it just depends what sort of mood I’m in). Up came a song by Iron Maiden, one of the UK’s heavy metal titans. The song, I recognised instantly, was called, “The evil that men do (goes on and on)” - a modification of the famous line in Shakespeare’s Julius Caesar - the full version being “The evil that men do lives after them; The good is oft interred with their bones.” As we watch with horror the TV footage of Putin’s advancing tanks, we pinch ourselves to check we are actually in the 21st Century. While Shakespeare’s quote is particularly trenchant today, the opposite is also true. Jenner, Koch, Pasteur and so many others built on each other’s research, knowledge and dogged hard work over the last two centuries to bequeath to humanity a gift that brings health and life. This is still work in progress. Our modern-day heroes and heroines of science have saved us from the worst ravages of COVID-19(COVID) and given us our lives back. Scientists are the new rock stars, thrust into the limelight over the last two years. We were lucky enough tonight to be addressed by the “lead singer” and some of the other virtuosos in the band (scientists, not Iron Maiden, although that would have been highly enlightening too).
A vast amount of ground was covered this evening, from science to morality to money and many other aspects of a topic, which for the first time in modern times, is at the forefront of the minds of the general population. While we grazed the issue from multiple directions, the question that pops out at the end is whether it is both possible and right to make money out of vaccinations. The answer must surely be yes and yes. While there are certainly those seen to have profiteered during the pandemic (mostly well-connected “suppliers” of PPE), profit has not, overall, come out of this a dirty word. You could argue that vaccines are something the state should provide - and indeed it does in terms of the patient. But while it can help, the state has neither the resources nor the infrastructure to deliver vaccines on its own. We received a reminder that, while we may think we have COVID on the run, there could be long-lasting effects and continued protection through vaccination is essential.
COVID may have shaken the world, but the flip side of the coin is that, necessity being the mother of invention, it turbocharged the whole science of vaccination. The billions of COVID vaccines yet to be produced and sold around the world are merely the tip of the iceberg. Could we have dared to dream that what traditionally took ten years can now be done in 12 months? In the dark days of 2020 this dream was indeed distant, but reality miraculously overtook the dream. In fact, as we heard this evening, the industry aspiration is to bring that down to 100 days or even less. Yes, this will protect us so much better against inevitable future pandemics, but that is just the beginning. With the technological advances made in the last two years, particularly in RNA, vaccinations for myriad serious diseases are now within our grasp. As national health services groan under the weight of ageing populations, the maxim of prevention being better than cure will come to the fore. Prevention of chronic diseases will save literally trillions of dollars over the next 10 years. Governments and investors alike will want to be involved in this paradigm shift in healthcare, craving exposure to the vaccination phenomenon. This is surely where the smart money is heading.
Are you sitting comfortably? Then we’ll begin...
Ed Harris - ThoughtLeader Editor
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Summary of ThoughtLeader Dinner, Tuesday 22nd February
Introduction from the Sponsor - Douglas Hansen-Luke - Chairman of Future Planet Capital
Future Planet Capital (FPC) was set up 6 years ago with the purpose of investing in the brightest minds on the planet from top universities and centres of innovation and research to invest in companies that could profitably address the key challenges currently facing the world. Two years ago, FPC invested in Vaccitech which was set up by Professors Hill and Gilbert of the Oxford vaccine. This vaccine has changed the world, being the most commonly used during the COVID pandemic. This has been done at some 10% of the cost of its competitors and has arguably saved more lives than any other. They are essentially investing in peace and healing. In the last year, they have also started collaborating with Professor Dan Peer of Tel Aviv University, who developed the first lipids that went into the BioNTech vaccine. Tel Aviv University has now set up a lab in Harwell, Oxfordshire. The objective is, with the help of the UK government, to create a vaccine which is effective, trusted, equitable and, of course, profitable. Therefore, tonight’s debate focuses on whether such things can be done both equitably and profitably.
Introducing tonight’s speaker
Professor Sir Adrian Hill was originally a medic but then moved on to biogenetics and founded the Jenner Institute in 2005. He has been at Oxford University for over 40 years and is of course best-known for heading the Oxford vaccine team. However, his start point is actually malaria and next year we hope to see the launch of a malaria vaccine, which will be a major global event. He is the Lakshmi Mittal Professor of Vaccinology and outside the lab has a passion for rugby and ballet.
Before Sir Adrian gave his exposition, nine pre-prepared scripts were read by members of the audience to set the scene for the forthcoming talk.
Script 1
2020 will be remembered for many things: deserted streets; skies without planes; and a glorious Mediterranean summer. It was also a year of restrictions, unprecedented in our lifetime. According to Dictionary.Com, the word ‘unprecedented’ was voted ‘Word of the Year”. One morning in October 2020, the word appeared in the frontpage headlines of eight national newspapers. In the Oxford English Dictionary, ‘unprecedented’ is described as follows:
“Without instance, never before known, unparalleled”.
The pandemic of 2020 was many things. However, one thing it was not, was unprecedented.
Script 2
Eighteen hundred years ago, a city in the heart of Europe was in the midst of a plague many times more deadly than the one we suffer today. That city was Rome, and the disease became known as the Antonine Plague. Victims would endure a viral attack for several weeks with progressively awful symptoms, too revolting to describe at dinner. It would prompt a contemporary writer at the time to say: “Like some beast, the sickness destroyed not just a few people but rampaged across whole cities and destroyed them”.
Script 3
There were seventy-five million people living in the Roman Empire at that time. It is estimated that ten million died in the Antonine Plague. It swept across the land indiscriminately. The elite, the rich and the poor, all succumbed to its ravages in equal measure. In AD 167, there was no defence against a viral attack, there were no epidemiologists, and no understanding of what was happening, and how to stop it. So, they prayed to their gods and hoped. Some even sent delegations to Apollo, asking for his advice. There was no Chris Whitty in Ancient Rome. Marcus Aurelius, who was popularised in the film Gladiator, described the Antonine Plague in his book, Meditations, as follows:
“To bear in mind constantly that all this has happened before and will do again – the same plot from beginning to end, the identical staging. All just the same. Only the people are different.”
How right he was.
Script 4
For eighteen hundred years, plagues, pandemics and disease left their cruel stamp on mankind time and time again. The Black Death raged across different continents three times between the 5th and 19th Centuries. Fatality was counted in millions, in some regions populations halved, villages disappeared and the course of history changed forever. Then, in 1918, the Spanish Flu infected 500 million people worldwide, killing 100 million in 18 months. Cholera, Yellow Fever and Polio all left their mark. But perhaps the deadliest of all was the Smallpox virus. Believed to have been in existence for three thousand years, it is impossible to calculate exactly how many perished over time. However, it is estimated to have killed at least 300 million in the 19th and 20th centuries alone.
Script 5
Today, we owe a huge debt of gratitude to a doctor practising in a rural English village towards the end of the 18th Century. Growing up, he heard that milk maids, who were renowned for their beautiful complexions, frequently contracted cowpox from the animals they tended, but typically did not get smallpox. Taking the liquid matter from a cowpox sore, he scratched it into the skin of an eight-year-old boy, who had smallpox. After a few days, the boy recovered. He named the matter taken from the cowpox sore ‘Vaccine’ after the Latin word ‘vacca’, meaning ‘cow’.
Script 6
That doctor’s name was Edward Jenner, and his discovery began the long journey towards the eradication of smallpox and the prevention of many deaths. In 1806, US President Thomas Jefferson wrote to Edward Jenner saying, “You have erased from human afflictions one of its greatest. Yours is the comfortable reflection that mankind can never forget that you have lived. Future nations will know by history only that the loathsome small-pox has existed and by you has been extirpated”. In 1967, a massive search and vaccination programme began with the aim of eradicating smallpox. It was a truly global effort. Ten years later, smallpox was finally declared eradicated.
Script 7
It took one hundred and fifty years to truly extirpate smallpox. Notwithstanding the research and development already in place, it has been an extraordinary achievement to create, manufacture and distribute an effective vaccine program against a novel virus in just two years. Perhaps one might even say it is ‘unprecedented’. Yesterday, Bloomberg’s COVID-19 Tracker System showed that a remarkable 10.4 billion doses of vaccine have been administered worldwide so far. However, it is concerning that vaccine dose rates in the most developed countries average 200 per 100 people, while in less wealthy countries that figure falls to around 30, and, in some of the poorest countries, 6. It is no surprise that health officials at the World Health Organisation now refer to COVID-19 as “a pandemic of the unvaccinated”.
Script 8
To help conceptualise the sheer number of viruses in existence, consider this: their current biomass has been estimated to be the equivalent of 75 million blue whales and, if placed end to end, the collective length of their virions would span 65 galaxies. Tom Freidman, the American political commentator and Pulitzer Prize winner, urged us not to get too complacent when he wrote - “Vaccines and antibiotics have made many infectious diseases a thing of the past. We have come to expect that public health and modern science can conquer all microbes. But nature is a formidable adversary”
Script 9
Dr Eric Yager, microbiologist at Albany University, said in November last year: “This pandemic has ushered in a new era of vaccine research. The combination of global collaboration and the development of mRNA vaccines is akin to a ‘landing-on-the moon moment’.“ We have come a long way since milkmaids and cows. But, as an unattributed source once said: ‘There is nothing so patient, in this world or any other, as a virus searching for a host’…
… Let’s find out more.
The Chairman had polled the guests as to their view on the motion. The result was 40% for, 60% against.
Professor Sir Adrian Hill - Director of the Jenner Institute and Lakshmi Mittal Professor of Vaccinology at the University of Oxford, Fellow of Magdalen College, Oxford. Leader in the field of malaria vaccine development and co-leader of the research team which produced the Oxford–AstraZeneca COVID-19 vaccine
Poets have been strangely silent on the subject of vaccines. Wordsworth would probably have been aware of the work of and quite possibly personally known Edward Jenner, but never a word about vaccines - just daffodils!
It has been an extraordinary two years for the whole world. Even pre-pandemic, the effects of vaccines should inspire awe, surprise and appreciation. They are doing an extraordinary job. 25 years ago, twice as many children died of infectious diseases as do today. This is largely due to the deployment of highly-effective, safe vaccines. 11 vaccines are now administered to children across the world from the wealthiest countries to the poorest regions of the developing world. There is around 90% global coverage of infant vaccines - something that would have been a game-changer during COVID. It is cost-effective because by the time these vaccines are delivered to the poorest parts of Burkina Faso, they have been licensed in rich countries where prices are much higher and manufacturers, mostly in Asia, have found a way to produce them at vast scale on thin profit margins, but still profitably. This makes them affordable for even the poorest countries.
This is a clear view on whether vaccines increase inequity. They generally do not as they are daily saving the lives of some of the poorest children in the world. This is achieved through a differential pricing model which is somewhat bizarre. 80% of the value of vaccines comes from high-income countries vaccinating roughly 10% of the number of people being vaccinated in low-income countries. This system was never planned but has evolved into one that works very well.
So therefore, in normal times, vaccinations cannot really be said to increase inequity. However, when COVID arrived, a coalition of international entities that arranged vaccinations - the WHO, UNICEF, GAVI (The Global Alliance for Vaccines and Immunization), and the newly-formed CEPI (The Coalition for Epidemic Preparedness Innovation) came together with a very sensible, attractive scheme called COVAX (COVID-19 Vaccines Global Access). All manufacturers would provide as many doses of vaccine as quickly as possible and these would be equitably distributed around the world. Last year, 9.5bn doses were distributed globally - an unprecedented achievement in this field. One might think we had now achieved a solution for all future pandemics. Of course, that would sadly be a Panglossian assumption. The key problem is inequity of vaccine distribution.
What went wrong? The distribution was both chaotic and extremely unfair. There was no globally-agreed distribution system. Such a task had never been undertaken in such a hurry before. There was a bidding war and naturally some countries could afford more than others. Some were better organised and, therefore, able to secure supplies before later bidders. As of now, only 16% of people in Africa have even had a single dose, compared to 80% in the UK and 99% in some countries. Costs have varied significantly; the Indian government was paying $1.50 per dose from the Serum Institute of India, up to $30 for the new mRNA vaccines. This was not what COVAX was trying to achieve. Nationalism also tainted the process. As it happened, the three countries with the largest militaries in the world - China, Russia, and the US, were also the three countries that did not license any vaccines other than their own. Theirs were each clearly the best so no need to license any others. They can’t all have been right.
When it comes to such a global emergency, you think of the big pharma companies and how much profit they are going to make. Four of them predominate in vaccine supply to high income countries - two in the US and two in Europe. In the end, only one of those became a major player in COVID-19 vaccines, which teaches us that we cannot always rely on big pharma to produce all the vaccines needed. Even the ethical question of “What is the right thing to do?” was not clear. The Chinese were criticised for prioritising their military for early vaccinations. Some vaccine manufacturers in Asia were vaccinating their own staff before distributing it externally. Most of those early vaccines had very little safety or efficacy data and these players were condemned for their actions. In the movie Contagion, that is precisely what the lead scientist does - injects herself before anyone else. Is that ethical? If the next pandemic were to be as deadly as Ebola - killing 60% of those affected, would you not expect those producing the vaccines to vaccinate themselves first? This is something the world needs to consider rather than just throw stones at each other.
In terms of distribution, several countries have individually consumed more COVID vaccine than the entire continent of Africa (consisting of 54 countries). That is hardly equitable. But how can that be corrected? The Africans are understandably furious and are trying to set up their own vaccine production facilities, but it is too late. So, while in normal times, vaccines generally are equitable, during the COVID-19 pandemic there simply wasn’t time to set up a system that prevented selfishness.
Vaccine technology is amazing and the COVID vaccines were a triumph of that technology - in particular, mRNA, which, to most people, appeared out of nowhere (in reality, decades of research went into it). This was also good for viral vectors - before COVID only one viral vector had been licensed in the West - J&J’s Ebola vaccine. Even the old-fashioned inactivated vaccines with which Louis Pasteur would have been familiar have done very well for what they were designed for. The standard way of producing vaccines - expressing a protein, finding an adjuvant, mixing it in - has turned out to be far too slow for a pandemic. That has been a complete surprise.
Ironically, the triumph of mRNA vaccines has further increased inequity due to the temperature requirement of the early mRNA vaccine. Poorer countries simply do not have the infrastructure to store and distribute vaccines at -80C - it worked fine in Europe and the US. Therefore, RNA vaccines must quickly address the issue of thermostability, which is why it is so exciting that the NeoVac initiative may well have solved this problem. That would be a huge step forward in terms of the fairness of distribution of RNA vaccines. In conclusion, in a pandemic situation, global public health policy collides with market economics, creating unfairness. Technology will play a key role in the solution - we need more facilities and more, newer vaccines. It is this that we must work on ahead of the next pandemic which sadly will inevitably come at some point.
The exposition was then followed by contributions from other experts.
Professor John Oxford - Professor at Queen Mary, University of London - leading expert on influenza, including bird flu, the 1918 Spanish Influenza, and HIV/AIDS.
The Past
A cataclysmic 100m people died from Spanish flu (so far 5m have died from COVID). A Viennese neurologist and fighter pilot - Constantin von Economo - in 1918 had mostly young men coming through his practice with head injuries from the war. Suddenly, his clientele started to change. He was increasingly seeing young men and women (the Spanish flu, unlike COVID, was predominantly fatal for the young aged 18-35) apparently suffering from Parkinson’s disease or cerebral palsy - shakiness, lack of balance and general weakness. They also suffered from intense lethargy and sleepiness - encephalitis lethargica. Within a few months, some French neurologists saw patients with similar conditions and soon these were occurring all over the world. By 1925, there were 5m cases of Von Economo’s disease across the world. Curiously, it was not contagious and nobody knew how one got it.
In the early 60s, another neurologist Oliver Sacks arrived at a hospital in New York. He was asked to look after a group of survivors of Von Economo’s disease, some of whom had been on the ward for 25 years. They were barely conscious. L-DOPA had recently been successfully used to treat Parkinson’s sufferers, so Sacks thought there would be little to lose by trying it on these patients. As described in his 1973 book “Awakenings”, these patients literally came back to life. Ladies who could play the piano 40 years ago could still play and they all spoke with their accents of 40 years prior. However, this miraculous effect was short-lived and the patients were, within weeks, back in their semi-catatonic state. Sacks thought that increasing the dose might help, but that was not possible.
A pair of epidemiologists from Atlanta, Georgia published a paper in the Lancet suggesting these patients were suffering the after-effects of infection with Spanish flu in 1918. The virus had got into their mid-brain area, either damaging it and leaving or possibly remaining there. Scientists probed brain and lung samples for definitive influenza RNA without success, but this was nonetheless a plausible explanation. Oliver Sacks turned out to be the key player in demonstrating that you can have a rare, long-lasting neurological impact after a large flu outbreak. A similar phenomenon also occurred with measles before MMR. A child would get measles and apparently recover. Then some time later, they would start to exhibit these same symptoms and ultimately die. Autopsies would show traces of measles virus in the brain. Of course, thanks to vaccines, children don’t get measles anymore. Likewise with polio, effects could be seen up to 30 years later
The key question now is whether COVID has a similar sting in its tail. It is a very strange virus. Unlike with other flu viruses, patients are not dying of pneumonia - it is from an as-yet poorly understood reaction of the immune system. The key point about this, therefore, is that we cannot be complacent about COVID-19. Just because fewer people are dying, we may yet find in the future that some who have caught it and recovered are still harbouring latent conditions that will present at a later date. In particular, we need to be wary of children catching it. While they do not appear to suffer at the time, the seeds of serious future illness may have been planted. Some scientists today feel like Cassandra - the Trojan priestess cursed to be able to tell the future but never to be believed. In truth, we will not know for four or five years yet whether COVID-19 is really over or not.
Professor Dan Peer - Director of the Laboratory of Precision NanoMedicine at Tel Aviv University
The future
His lab was the first to show systemic delivery of mRNA in animals. This was some years ago and felt like science fiction. However, its transition to reality was rapid. He wrote a grant in 2008 to the National Institute of Health entitled “mRNA which is modified with lipid nanoparticles as a new platform for vaccines.” There was almost no interest whatsoever. The comments from the panel were effectively that it was imaginary, could not be done and an altogether stupid idea. In December 2020 when the Pfizer vaccine was approved, he was able to remind the NIH panel of their earlier comments.
They were approached by BioNTech to collaborate on some of their lipids, which resulted in a few licensing deals and the rest is history. The key is the future. We have learned over the last two years the challenges in making really good mRNA vaccines, key among which is thermostability. They must be stable in a regular fridge or even at room temperature. Also, the ability to entrap large payloads in lipid nanoparticles opens up new avenues for so many diseases - not only regular infectious diseases but also cancer, and metabolic diseases. But even in the sphere of regular infectious diseases there is so much scope to create new and better vaccines.
They have developed a proprietary new lipid library which they have started testing. Around a year ago they came to the UK and set up, with Adrian Hill and others, Neovac. It has huge potential. The ability to entrap large payloads into a single particle is already at the ‘proof of concept’ stage. Thermostability for at least one year in a regular fridge or one month at room temperature is an ongoing study. This could change the world.
Marianne Talbot - Director Of Studies in Philosophy at the University of Oxford's Department for Continuing Education
The human aspect
Most of us were brought up both to tell the truth and be kind. However, life throws up plenty of moral dilemmas when these can be mutually exclusive (when your mother asks your opinion on her terrible haircut, for example). The COVID-19 vaccine has created various moral dilemmas; we ought to protect people in our own country. However, we also ought to protect those in poor countries who can’t afford to protect themselves. Given a finite number of vaccine doses, you cannot do both. Many different interests impact on these decisions.
The second moral dilemma; we ought to protect our most vulnerable citizens, but we also ought not to force citizens to do something against their will. If we are to look after people in care homes, then surely both carers and patients must be vaccinated. What if the carers don’t want to be vaccinated? Do we force them? Also, given that none of us are safe until all of us are safe, do we introduce vaccine passports and, if so, are we prepared for those who don’t want a vaccine to be denied access to clubs, restaurants and foreign travel? Is that not unfair coercion?
There are different approaches to moral dilemmas; we can insist that one “ought” is more important than the other - for example, that truth-telling is always more important than kindness. Alternatively, we can decide that kindness trumps the truth. We all know people who exhibit both philosophies. The answer is that each situation must be judged on its own merits. Do we prioritise vaccination for children in the UK who appear to be unaffected by COVID, or the elderly in poor countries who are?
The other approach to the moral dilemma is to reinterpret the key concepts. In the case of Mum’s bad haircut, telling her the truth about it can be rationalised as being cruel to be kind, so we have ticked both boxes. We could conversely say that, if we lie in this case it is not a real lie - just a white lie. In the case of vaccines for carers, we can approach the question by saying that we are not forcing them to be vaccinated insofar as we are not forcing them to be carers. Equally, with vaccination passports, we present the restrictions imposed on the unvaccinated as being their free choice.
Moral rules will often clash, but that forces us to think about our values - what is a lie? What is it to be kind? What is it to protect people? What is it to force people to do things etc.? Aristotle took the view that there are no moral rules, but that we need to engage in moral reasoning. This is an ability exclusively enjoyed by humans. COVID-19 vaccines have faced us with a number of moral dilemmas. We have no choice but to deal with them while trying in some way to keep all the virtuous qualities in play.
Jules Haggerty - Head of Centre of Excellence - Lipid NanoParticle at CPI (Centre for Process Innovation)
Public / private collaboration
How can we use government-funded infrastructure created over the last 5-10 years to support and accelerate medicine and vaccine development? In early 2020, the UK biomanufacturing community was already mobilising - this was before the vaccine taskforce was even thought about. This close-knit community set about finding out who had which relevant capabilities in terms of RNA vaccine manufacture and distribution. It turned out there was not much. By chance, CPI had just been doing some work around lipid nanoparticle technologies that would lead to RNA. CPI thus turned out to be the best qualified entity to take care of UK manufacture and supply of the RNA once the taskforce was convened. Their first project was a collaboration with Imperial College which worked well. The fact that for their clinical trial material they had to source RNA and other materials and technology from the USA and Austria did demonstrate that there wasn’t much to work with in the UK. It has been a rollercoaster few years working with the Vaccine Taskforce with changing strategies and partners. However, running through all their work was a strong desire to be able to manufacture and supply RNA vaccines from the UK and not be reliant on sources abroad. In that they succeeded. They have engaged in R&D and set up a manufacturing facility in Darlington for a fraction of the cost of most other manufacturing facilities.
What will they use it for? CPI only exists to partner and collaborate. They will be translating academic research and help companies grow to the benefit of society and help economic growth in the UK. The Darlington facility will be offered out to the new generation of companies to progress their vaccine candidates into the clinic as quickly as possible. In this pandemic, quick decisions had to be taken and regulators had to be nimble. The government found a new way of making decisions without going through 20 layers of bureaucracy. If they could do it then, then why not now? You have to take more risks and do things in parallel. You need finance up front, but it’s not impossible.
CPI’s collaboration model tackles the really big challenges that trouble industry and society. It is competitive, but academia, government and industry can work together using a shared risk and reward model. It demonstrates the art of the possible. When finance is needed, there is already a proof of concept in place. An example is CPI’s collaboration with NeoVac. The vaccines taskforce asked them to survey the UK landscape regarding RNA and lipid nanoparticles to assess what was extant and what was missing from our capabilities. Equity was a big issue - the vaccine cannot be $30 a dose around the world. Equally, the UK government did not want to be dependent on one overseas company demanding licence fees for a proprietary lipid. NeoVac has some IP (Intellectual Property) that really addresses some of those key issues. Combining the manufacturing capability and RNA supply of CPI with NeoVac’s IP portfolio will demonstrate proof of concept. This goes way beyond COVID. The LNP (Lipid NanoParticle) technology is useful not just for delivering RNA but also lots of next-generation therapy - the list is endless.
Christopher Egerton-Warburton - Partner at Lion's Head Global Partners
Costs
When the UK government wanted to fund GAVI (Global Alliance for Vaccines and Immunization), IFFIm (the International Finance Facility for Immunisation) was at hand. It was founded in 2006 on the idea that private investors and government donors can work together to have a greater, more immediate impact on global health. This entity devised a way to issue bonds to fund vaccines. Following the Ebola crisis, he was contacted by a major WHO figure, who had also co-founded GAVI, reminding him of Bill Gates’s famous remark to Angela Merkel that “This should never happen again.” Out of this, CEPI was formed which crystallised his thoughts on what needed to be done to bring new vaccines to the world.
The focus of GAVI is cost - how can vaccines be made cheaper, to the point where most Western manufacturers have largely exited the space and bulk manufacturing has moved to developing countries such as India, where it can be done at incredibly low cost. Lives are saved literally for pennies. It has been incredibly successful and the UK has been a huge supporter of GAVI. Early in the COVID-19 outbreak, he was invited to join a meeting at the World Bank in Washington. There were a surprisingly small number of people there trying to figure out what on earth to do about COVID. This was the nightmare they had been fearing and they realised they were not remotely ready for it in terms of products and science. The UK had not joined CEPI, but thankfully Chris Whitty had helped set up a similar body which had channelled funds into the Jenner Institute and others.
He was asked to write a paper for the Bill Gates Foundation on which vaccines he believed would make it. His initial thought was that COVID-19 had come too soon for mRNA technology - that governments and regulators would not be prepared to allow these vaccines to be administered to millions of people without years of trials to test for secondary impacts etc. Normally, regulators are particularly cautious about vaccines, lest they make otherwise healthy people ill. Vaccines do not change. The BCG (Bacillus Calmette–Guérin) vaccine against TB hasn’t been changed since 1918.
There was a concept at GAVI that vaccines should be free. This came from enlightened self-interest. It is not just about saving people in poor countries - it is also about preventing infectious diseases from migrating from poor countries to rich. COVID-19 presented a complex horror story. All vaccines had to be free. Everybody had to be vaccinated. Imagine the difference in cost between vaccinating a cohort of people and jabbing the entire population of the globe. HPV (Human papillomavirus vaccine) almost completely prevents cervical cancer in women and throat cancer in men. However, because this was only rolled out year by year, millions in the future will die from vaccine-preventable cancer. So, the task of rolling out for free a vaccine that did not yet exist to everyone on the planet was a daunting task.
His sense in writing this paper was that the Oxford vaccine would probably be the best candidate but spoke to Adrian Hill to tighten up a few facts. The rest is history. There is more to do, however. The vision must be to be able to create a vaccine in 100 days. Much of that is about regulation and the realisation that we already have some good tools and models. CEPI set up many models on the basis that of 20 vaccines, 15 would likely fail. What is actually more likely is that either all would succeed, or all fail on the basis of whether or not they produced an effective protective antigen. COVID-19 has arguably fast-forwarded biochemistry by 10-15 years. We must now take what we have learned, in order to ensure that vaccines are equitable.
He suspects that when the history books are written, the Oxford Ebola vaccine would have been one of the best, even though it never got licensed. Novavax is probably the best COVID-19 vaccine we have created, but represents only a fraction of doses administered. Science is not fair. mRNA vaccines have been shown to be a very powerful tool in shutting down an epidemic. If such vaccines can be made cheaper and more thermostable, then the inequity question disappears.
Q & A session
Q How can we avoid forgetting what we have learned so that when this happens again we avoid the same mistakes?
A History does repeat itself. Ebola did not only occur in West Africa. People brought it back to the UK, were quarantined, ended up in ICU and some sadly died. At that time, some money was made available - it conjures a rueful smile to think how generous David Cameron’s government felt its £50m contribution was, albeit that it was later doubled. We need to develop all technologies that we have and we know so much more in the wake of COVID. The main thing, and this is not hugely expensive, is that we need to build proper manufacturing facilities. What made a huge difference to the Oxford team was that they had already been working with the world’s largest vaccine manufacturer (AstraZeneca) on a more obscure disease, so when COVID-19 arrived in March 2020 and the Oxford vaccine was licensed nine months later, this collaboration was already well-established. Even in mid-2020, the Gates foundation was talking of funding manufacturing facilities in each continent to help in the struggle against COVID. This went a bit quiet when someone was brave enough to point out that these would take two years to build and a third to get them approved. Then they would have to be staffed with people with considerable experience of manufacturing vaccines - all in, a rather complex process. These facilities do indeed need building across the world in preparation for the next pandemic. It will cost money but is more cost-effective than certain other defences. We are more likely to have another pandemic than a nuclear war (Adrian might revise his thoughts on that given events since then). The circumstances that gave rise to this pandemic are still there. We should perhaps focus more on health and less on war.
Q How do we devise incentives for the vaccine industry to produce one-shot vaccines which would necessarily have hugely front-loaded sales?
A There are several ways to go. Thermostability is crucial - if you can store vaccines in a fridge for a year, that would be ground-breaking. Take the example of Israel. Early in the pandemic, there was a strategic decision to strike a deal with all the companies developing vaccines. They all got paid, despite there not yet being a vaccine to deliver. They were effectively buying the rights to priority distribution of the future vaccines, and it worked for Israel strategically. The price, of course, was very high.
There are ways to reduce risks. People had not appreciated the scale of the thermostability issue. Specialised containers are being produced that help with this.
Q This is a question about Biosecurity. The scientists in the room obviously are driven by good intentions. As we are seeing in Ukraine, not all people share those good intentions. Looking back in history, gas - the first weapon of mass destruction - was used in WW1. Between the wars, there was a preoccupation with sarin gas. Thankfully, it was never used. Then 1945 saw the creation of the nuclear bomb. We went through the Cold War during which the destruction of the whole of society was a very real possibility. We have now reached an age where biological weapons can be deliberately delivered and deployed by actors with aggressive intent - something that can spread swiftly through a society and have a high mortality rate. While we are in the fortunate position now with COVID-19 being a relatively mild disease, despite its high transmissibility, it is highly questionable as to whether this was a disease that evolved naturally. Is it now not the job of the nation state to create a biosecurity construct whereby potential biochemical threats, particularly from the likes of China, are analysed and antidotes developed and manufactured, in tandem with the development of vaccines against naturally-occurring diseases?
A There are already thoughts along these lines. There are strategies for producing expensive antibodies or vaccines along “pancoronavirus” lines. Luckily, there are only seven classes of pathogen, and it will soon be possible to create generic vaccines against many of them. Until COVID, the only people who cared about coronaviruses were veterinary vaccinologists. They were a huge problem for chickens and other livestock and many vaccines were developed for them, but humans had only mostly encountered SARS and MERS. Sitting around the table, we were all no doubt infected by a variety of coronaviruses which thankfully don’t cause much disease. We should be reassured to know that it is actually very difficult to create bioterrorist agents. You have to be able to test them to see if they are more transmissible and virulent. COVID-19 has been through billions of people over the last two years, mutating all the while, and it has taken quite a while for it to mutate into something highly transmissible. We are lucky that its virulence has been reduced.
Q Was Brexit a pro or a con when it came to Europe’s “Vaccine Wars”?
A The scientists involved in the Oxford vaccine were adamant that it should not be labelled a “British” vaccine draped in the Union Jack, despite the fact that the UK government largely funded it. It was unfortunate that a German tabloid in particular decided to run a story that the Oxford vaccine was ineffective. This may indeed have been symptomatic of Brexit tensions. Although this resolved itself in the end, it certainly dented vaccine confidence in the short term. One key revelation, though, in terms of policy is you should not listen to the groups of academic experts in any one country. Instead, you should listen to the regulators in each country as they communicate amongst themselves constantly on questions of safety. The groups of academic advisors changed from week to week. The newspapers didn’t want to publish the findings of the regulators - only the most extreme views on both sides.
Q Tonight’s debate is about equity - what works and is fair for everybody. Is it right for a country to pursue the safety of its own people ahead of others? Is there a way in which government can speed up the process and what is it about nationalism that makes it so hard for countries to cooperate?
A The Israeli experience proved to be highly efficient. Only 9,000 people died from COVID. This number was very similar to two bad years of ‘flu. Starting vaccination very early in December 2020 brought Israel very quickly to a high level of protection. They paid more than treble the retail price for what at the time was a risky technology. There was criticism and dissent within the government, but the result was that Israel’s five waves of infection did not do too much harm. Angela Merkel negotiated a great price with Pfizer BioNTech, but that meant Germany was the last to get the vaccines. The founder of BioNTech didn’t himself get vaccinated until it was “his turn”. The outcomes of these different strategies tell their own story. Israel arguably suffered almost no excess deaths from COVID.
The UK also started vaccination early, but our death rates did not stay low. Why? The perceived compliance of the British public? The decision to lock down a week later than advised may have had a profound effect. There is no point in giving people three doses of vaccine against a particular variant when the virus is rampaging and mutating around the world. It would be better to be a little more generous in our distribution overseas. We should increase our help to developing countries in setting up their own manufacturing facilities - this can be done without losing control of our IP.
Adrian has dreamt of countries producing vaccines A, B, C and D with nobody knowing which one was from where. When we go to the GP to get any other vaccines, we don’t ask or know who made them and in which country. Our only concern is whether they are effective and so it should also be with COVID-19 vaccines.
Q What lessons around equity and access learned from vaccines can be applied to other life sciences and pharma? In these other areas, because there is less reliance on public / private partnerships and more on private financing through pharma companies and recovering the cost of research through the patent process, there are questions about where the research effort is directed. Imperfect though equity in vaccines may be, it is better than that in the rest of pharma, even from the perspective of being a champion of the role of private pharma in innovation. It has nonetheless been highlighted that there is a lack of research effort in combating antimicrobial resistance and producing new antibiotics. How do we achieve an effective direction of research dollars across the life science sector?
A We live in a capitalist society - we have to work with the system. We heard about the massive bet that Israel made on the COVID-19 vaccines. These are not the sort of decisions that governments usually make. In normal circumstances, such a gamble would likely prompt too many recriminations. Over the years, big pharma like GSK, Pfizer, Merck and others have received bloody noses by pouring money and capacity into various vaccines. We need these big companies and they have shareholders. Ultimately, we cannot expect them to act against their own interests.
We can learn things from RNA in that it is a platform technology that can be applicable to the 100-day challenge. That is applicable to a range of other therapeutic uses. There could be technological transfers that may have an impact in reducing costs. The issue of funding is more difficult. Big pharma’s programmes are pre-arranged. If they are working on a malaria programme you can’t suddenly ask them to produce a cancer therapy available at a particular cost. This could be an area where more charitable and philanthropic organisations can step in.
Q Money has poured into the development of COVID-19 vaccines in the last two years. Are there any other areas that might benefit from a spillover effect?
A Closely related areas like flu may well benefit but it is also possible that the likes of shingles and HIV could also benefit. The next step could well be cancer. Many of these RNA companies were based in cancer research and they might go back to that - for example specialist tumour vaccines. The other areas might be protein-replacement therapies such as cystic fibrosis and other genetic disorders. The technologies are applicable, but manufacturing would need to be scaled up.
Q What is the prognosis for the malaria vaccine?
A The vaccine for Plasmodium falciparumis - the most widespread and deadly (640,000 deaths in 2020) strain is in phase III trials. Efficacy is currently at 70% - we would like it to be at 95%. There is a vaccine from the Serum Institute of India - made in Oxford. Their approach to malaria is not to push one but four and, subject to funding, the main principles have been cracked. The other good news is that they can manufacture it at about $1 a dose.
Summations for and against the motion:
For (proposed by your editor)
This title does raise the notion that vaccination could somehow, potentially, be regarded as a bad thing. It’s obviously not. But the word inequity, in contrast with inequality, implies a degree of injustice or unfairness, whereas inequality is simply a quantitative imbalance. Of course, inequality is also often unfair, but then life isn’t fair and that has been starkly demonstrated by the COVID-19 pandemic.
There can be little argument about whether pandemics increase inequity. The worst off in society have suffered disproportionately financially and medically - while the wealth of the already stratospherically rich has gone into orbit - sometimes literally. On the basis that vaccines mitigate the effects of pandemics, you could argue that they therefore mitigate that inequity. In one sense, that is true, but of course that beneficial effect is felt unequally, so with the best will in the world, vaccines do increase inequity to the extent that those with wealth, health and education benefit disproportionately.
For the purposes of vaccines, you can roughly divide the global population into 4 groups; those who do or do not have access to vaccines and those who do or do not (or would or would not) choose to take them. Since the days of Jenner himself there have been anti-vaxxers, suspicious of new science and the powers that back it, but I suspect relatively few base their beliefs on a fear of inequity. Vaccines are only effective if people can be persuaded to have them. While some anti-vaxxers have done their homework and come to different conclusions to the majority, many, but not all, are among the less educated, making them susceptible to those deliberately spreading misinformation, or who have a natural tendency to be mistrustful of any government initiative. Others adopted a rather more paradoxical position. Believing themselves to be fit and healthy, they saw no reason to take the infinitesimal risk of vaccination themselves, while relishing the freedoms they enjoyed as a result of millions of others doing so.
Nobody, I would assume, would suggest that vaccination is a root cause of inequity, but does exacerbate existing inequity within and between societies. We, in the UK, are hugely lucky to have the wealth of talent and scientific knowledge exemplified by Professor Hill and his colleagues, coupled with the wherewithal to administer the fruits of their labours to protect the population from a novel and vicious disease. However, this at times has led to a rather unattractive “I’m alright Jack” mentality as we watched with relish as politicians in France and other European nations tied themselves up in knots and stumbled with their messaging while we sailed ahead with our impressive vaccination programme. You might even say that, shamefully, some jingoistically enjoyed pipping our neighbours to the post, ignoring what that meant in terms of needless suffering.
Vaccines during this pandemic, setting aside the small matter of saving millions of lives, have been used as political and economic assets. If Boris Johnson survives in office, it will only be because of the UK’s highly-successful vaccination programme - an undeniable achievement for which even his detractors would grudgingly have to give him a shred of credit. Being an incorrigible cynic, I would say that even the calls from the WHO for the rich countries to share their spoils with the developing world are not purely altruistic. While nobody wants to see people dying, the developing world is a key part of the global supply chain which makes us self-interested.
Then there are those demanding shareholders. While it is clearly unrealistic to have suggested that the key players behind the vaccines would make them available to developing countries either before or concurrently with their host nations, there is certainly inequity in how different companies have behaved in terms of pricing. Not mentioning any names of course, some appear to be capitalising more than others. While all vaccine producers are cutting prices for sales to countries which can’t afford them, it is interesting that in 2022, one key producer in particular is forecast to focus its sales almost entirely on high-income countries (presumably on full margin) while, for example, Oxford / Astra Zeneca’s sales are expected to be spread across the global socio-economic spectrum.
Therefore, I would argue that, while vaccines do not necessarily cause inequity, they do increase it. Having priority domestic access to any value-added and ubiquitously-needed resource will have that effect. Look at the current energy crisis. The UK being a world-beater in medical science gives us a natural advantage when it comes to creating new vaccines. Of course, it is not the vaccines themselves that increase inequity - it is the financial and political power they represent. We should all be proud, however, that Oxford are setting an example and leading the way among vaccine producers in keeping that inequity to a minimum.
Against - Jack Mitchell - Barrister at Old Square Chambers
Inequity is indeed a lack of fairness and justice. One of the concepts was that mRNA was too soon. Distribution is not equitable, but science is also not fair, so does that support or oppose the position as to whether vaccinations in themselves are a proponent of inequity? They are a collaboration between public and private. Why aren’t we putting vaccines into Coca Cola - the most widely distributed soft drink worldwide. The only two countries in the world where it is not number one are France (Orangina) and Scotland (Irn Bru). Darlington in five months were able to create what was necessary in a pandemic, not just for this country but beyond. The concept of thermoaccess is also key. If we want to think about inequity, vaccines are not inequitable - they have merely held up a mirror to our society which is full of inequity. The fact that we can now see that better might help us to reduce it. Context was another theme as to why the motion should be opposed. Thinking of Cassandra, what does the future hold? The issue of thermostability is being addressed, which could mean vaccines could be stored at room temperature for a month. Could the mirror of inequity be about to shatter? To quote Professor Sir Adrian himself, “Vaccines don’t increase inequity”. You are therefore invited to oppose the motion.
The room voted overwhelmingly to oppose the motion (to the chagrin of your editor).
The evening ended with a fulsome vote of thanks from Lord Wei - Social Entrepreneur and member of the Advisory Board of Future Planet Capital.
Conclusion:
It must surely be rare for so many scientific luminaries to address outsiders in private session. All those present were the beneficiaries of the real inside track on what is going on in the world of vaccines. We were in the presence of the people who actually did it - who changed the world. Without their skill and dedication, along with that of their colleagues, we could all well still be cowering in mandated isolation. Yet more extraordinarily, millions of people around the world who today are walking around alive and well could be, well, dead. Then there is the countless number of people who will benefit from vaccines yet to be developed. The internet and mobile phones were game-changers (I was going to say killer apps but that doesn’t really work here), but vaccines are the new “saviour app”. Of course, developing vaccines costs money - lots of it - but this is surely an investment in the future of our species.
Soon enough, investment managers will have to explain themselves for not having an exposure…
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