Hard-to-swallow truth about a future vaccine

Eugene Gu, The Independent

When pharmaceutical company Moderna issued a press release about the promising results of its Phase I clinical trial for a coronavirus vaccine, the media and the markets went wild. The New York Times ran a story that went viral on Twitter, racking up millions of views as social media influencers and doctors alike shared it far and wide. Moderna’s stock price shot up 20 per cent and several peer companies like Novavax rallied even higher at more than 30 per cent.

But was it justified?

The news cycle in the era of the coronavirus pandemic feels like tidal waves of hope and fear on steroids. Perhaps that’s because with more than 36 million Americans losing their jobs and more than 90,000 losing their lives, everyone is desperately looking for the light at the end of the tunnel. COVID-19 is taking an unprecedented physical and psychological toll on the American people and so small bits of potentially good news that should be taken with a grain of salt can end up dominating the headlines. People turn molehills into mountains because we really need and want a game-changer right now. But the truth is the truth regardless of what we want or feel, especially in science and medicine.

Phase I clinical trials simply test the safety of a drug or vaccine in a small number of healthy volunteers — usually brave and naïve college students — while Phase II trials are responsible for testing its effectiveness in a larger number of subjects. Such a hyped-up and exuberant response to a Phase I trial is rare and nearly unheard of, even in the extraordinary setting of Covid-19. This is especially the case since so little information is gleaned from an investigational drug in Phase I that has many more hurdles to overcome before it successfully gets to market. In fact, 77 per cent of vaccines for infectious diseases make it through Phase I, but only 33 per cent make it through the entire process overall.

Moreover, upon examining Moderna’s non-peer reviewed press release, the actual data on the vaccine’s success is even more flimsy. According to the document, of the 45 patients who received the vaccine, the data on “neutralizing antibody data are available only for the first four participants in each of the 25-microgram and 100-microgram dose level cohorts.” In other words, that means that when it comes to finding out whether the vaccine elicits an antibody response that could potentially fight the coronavirus, they only had data on eight patients. That’s not enough to do any type of statistical analysis and it also brings into question the status of the other 37 patients who also received the vaccine.

Moreover, when it comes to determining whether the “neutralizing antibodies” were clinically effective against the coronavirus, the only data Moderna eluded to were from mice. Not only are there huge differences between mice and men, but history also proves that success in animal models is often not replicated in human studies. This is especially the case for Moderna’s messenger RNA vaccine, which would be the world’s first to ever reach the market if it passes clinical trials.

In many ways, the vaccine almost behaves like an RNA virus itself except that it hijacks your cells to produce the parts of the virus, like the spike protein, rather than the whole virus. Some messenger RNA vaccines are even self-amplifying. That means they encode not only the protein antigen of interest to elicit an immune response but also produce their own RNA dependent RNA polymerase, so that they can force the cell to replicate more copies of it. In fact, public acceptance of this new paradigm is not something to be easily dismissed nor taken for granted. There are unique and unknown risks to messenger RNA vaccines, including the possibility that they generate strong type I interferon responses that could lead to inflammation and autoimmune conditions.

That is not to say there aren’t also great advantages to having messenger RNA vaccines too. For example, they can be mass-produced cost-effectively on a large scale necessary for the worldwide vaccination efforts that we desperately need for the coronavirus pandemic. They also do not require uninterrupted cold storage that makes vaccines challenging to distribute in poor countries and rural areas with unreliable refrigeration at the point of care. However, the fact remains that messenger RNA vaccines have never before been brought to market for human patients. So the hype surrounding Moderna’s vaccine requires us to take not one but two leaps of faith — that it works for a never-before-seen virus and in a never-before-seen way.

But perhaps the most important question to ask about Moderna’s new messenger RNA vaccine is not scientific nor technical but one of ethics and morality. When it comes to the United States and its private healthcare system, pharmaceutical companies have a long and sordid history of putting profits over people and human lives. Pricing and access to drugs — like insulin, for example — have been limited to those who can afford it at the deadly expense of those who cannot.

When Dr Frederick Banting and Dr Charles Best discovered insulin in 1921, they sold their patent for $1 because they could not bear the idea of profiting from a drug that was meant to save human lives. Yet pharmaceutical companies like Eli Lilly have skyrocketed the price of insulin using a process called “evergreening,” where they make incremental changes to the drug in order to renew their patents in perpetuity. Could the same thing happen with Moderna’s new and revolutionary messenger RNA vaccine for the coronavirus? If American pharmaceutical companies become the world’s gatekeepers for the vaccine, will they allow everyone to have it at low cost or will they prioritize only the rich and powerful?

Oxford Vaccine Group has a competing coronavirus vaccine called ChAdOx1 nCoV-19. It works by genetically re-programming the adenovirus — a DNA virus that causes a mild cold in humans and elicits a strong immune response — to express the coronavirus’s spike protein on the surface of itself. Then the adenovirus, which can be modified not to replicate nor become infectious, is injected as a vaccine that allows our bodies to generate protective antibodies and immunological memory to fight the coronavirus.

Unlike Moderna’s messenger RNA vaccine, the Oxford vaccine does not need to invade and hijack our cells’ own machinery to produce the coronavirus’s spike protein and instead hijacks the adenovirus’s machinery before it even comes into our body. From a medical and clinical perspective, there is less risk of generating a type I interferon response and autoimmunity because there is no messenger RNA floating around our blood, invading our cells.

But most importantly, the Oxford Vaccine Group is part of a universal healthcare system called the NHS within the UK. As such, there is much less potential for price-gouging and barriers to access for the eventual coronavirus vaccine compared to Moderna. If the undeserved investor and media hype for Moderna’s messenger RNA coronavirus vaccine allows it to overtake all competitors around the world, then we may be left with a potentially more dangerous and unknown vaccine that many of us may not even be able to afford. So let’s have an even playing field here.
Let’s base our excitement and exuberance on the actual facts and evidence and data rather than our labile emotions and feelings. We are all in this together, and that includes poor people in America and poor people in poor countries around the world who deserve an eventual coronavirus vaccine that is safe, effective, and — last but not least — affordable.