Since the beginning of the COVID-19 pandemic there has been discussion of the prospects of a vaccine targeting the SARS-CoV-2 virus that causes the illness. Research quickly got underway in numerous pharmaceutical companies around the world, some building on earlier research involving SARS-CoV-1. By the late Spring and early Summer the experts were saying that, if all goes well, we might expect approval for an effective vaccine by 2021. In August I wrote here, “I am hopeful that one of the vaccines in development will legitimately cross the finish line by the end of the year”.
We are not quite there yet, but if the preliminary evidence announced recently by Pfizer and BioNTech holds up, then we could get an emergency use authorization (EUA) from the FDA sometime in December. So what is the status of this vaccine?
This is exciting news for a reason that is likely to get overshadowed by its application to the pandemic – this is an mRNA vaccine. If it gets approved it would be the first mRNA vaccine in use. The technology first appeared in the literature in 1990, so this has been in development for 30 years. There were many hurdles to overcome, but they eventually were solved.
Vaccines work by introducing material into the body that will provoke a specific adaptive immune response. This could be an attenuated virus, a killed virus, or a viral protein, for example. An mRNA vaccine works by introducing messenger RNA, the genetic material that is used to make (translate) proteins. The technology was developed so that the introduced mRNA is taken up by cells and used to make viral proteins, which then provoke the desired immune response. Why not just inject the proteins themselves? You can, but mRNA has several advantages, including that it can be mass-produced more quickly and cheaply than a protein-based vaccine. If this vaccine works and gets approval it may usher in a new era of vaccine production that could have benefit far beyond the current pandemic.
Regarding the Pfizer-BioNTech vaccine specifically, we only have early results and these have not yet been peer reviewed, so we are dependent on what the companies are telling us. The phase 3 trial involves almost 44,000 volunteers so far, half of which were given the vaccine and the other half a placebo (a saline injection without any active ingredient). Each group receives two doses about 28 days apart. Then the researchers just wait and see how many people in each group contract COVID. They can also track the severity of the illness and the outcomes in those who do get sick, and of course they will track any potential side effects from the vaccine itself. The companies now report that 94 of the study participants have contracted COVID-19, with 90% fewer cases in the vaccine group compared to the control group.
A 90% efficacy would be great, if this holds up when the final data is analyzed and reviewed. Expectations were that the FDA would consider approving a vaccine if it had at least 50% efficacy, so this is high above that low bar. The fact that two doses are required is unfortunate, because it means two doses have to be manufactured and distributed for each person protected, and in the real world many people don’t show up for the second dose. But this is not a deal-killer, just less than optimal. Early reports indicate that the side effects are a little worse than the flu vaccine, mostly irritation at the injection site and fevers.
In negotiations with the FDA it was decided that they would consider EUA only after 50% of all study participants have been followed for a minimum of 2 months, which will happen by the end of November. This is to ensure that enough people have been followed for long enough to monitor for serious side effects. Of course, this will not capture all the potential side effects that can emerge when the vaccine is given to millions or even billions of people, but it is a reasonable process to balance risk vs benefit. Then after release, if that happens, there will be continued monitoring as is standard procedure.
Pfizer says it will be able to produce 50 million doses by the end of 2020 (enough for 25 million people) and another 1.3 billion doses in 2021. If the FDA grants an EUA after looking at the data, then by the end of the year the vaccine can start distribution to high risk individuals and those most likely to catch and spread the virus, such as front-line workers. From there the vaccine can be released to the general population. The UK-based Joint Committee on Vaccination and Immunisation (JCVI) has issued the following guidelines on who gets it first:
- Older adults in a care home and care home workers
- All those aged 80 and over and health and social care workers, though they may move up the list
- Anyone 75 and over
- People aged 70 and over
- All those aged 65 and over
- High-risk adults under 65
- Moderate-risk adults under 65
- All those aged 60 and over
- All those 55 and over
- All those aged 50 and over
- The rest of the population, with priority yet to be determined.
Pfizer is an American company but with an international footprint, and BioNTech is a German company. Which countries get the vaccine first will largely depend on regulatory approval. It is likely the FDA will be the first to grant an EUA, but the companies will also seek approval from the European Medicines Agency (EMA) and the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK. Given all this it is hard to say exactly how the vaccine will be distributed internationally, but it is likely that many if not most Americans and Europeans could be vaccinated by the end of 2021. And of course there are many other vaccines in the works around the world and it is likely that several will become available over the next year.
All told, this is very good news. An effective vaccine will definitely have a positive impact on the pandemic, and will likely be a game-changer. Hopefully the preliminary data will hold up, and no serious side effects will emerge. It should also not be missed that this was the fastest that a vaccine has been developed and (hopefully) soon to be approved in history, and that this vaccine is the first of a new vaccine technology that also promises to be a significant advance.