By: Rachel Levene, PhD Candidate in Molecular Microbiology at Tufts University School of Medicine and daughter of Dr. Eric Levene, Chester Pediatrics.
We’ve all seen the wonderful news about Pfizer’s and Moderna’s COVID vaccine trials – preliminary estimates of greater than 90% efficacy. I, too, am extremely excited and hopeful, especially since I am a participant in Pfizer's trial. I’m here to break down what this all means and when we might actually be able to roll up our sleeves and get vaccinated.
How do these vaccines work?
Pfizer’s and Moderna’s vaccines were made using new vaccine technology called mRNA. Their vaccines are a message that encodes the instructions for our cells to make part of the protein on the surface of SARS-CoV-2 (the virus that causes COVID-19). Even though the cell is making a viral protein, it cannot give anyone COVID-19 as the virus needs all its proteins to cause infection. The thought is that the immune system will make antibodies against this protein, much like what happens when someone gets naturally infected. The thought is that these antibodies will neutralize SARS-CoV-2 before it enters any cells and causes illness. Both require two doses, spaced three-four weeks apart.
One challenge of this new vaccine technology is how it is stored and shipped. mRNA is notoriously unstable and it needs to be kept at ultra-cold temperatures. Pfizer’s vaccine needs to be stored at -104°F, something regular freezers simply cannot do. Moderna’s can be stored for a limited period of time in a regular freezer and/or fridge. This presents a shipping problem and problem for distributing the vaccine in areas that do not have major medical centers that have access to ultra-freezers. Both companies and the government are working on distribution plans and how long the vaccines can remain stable in regular fridges and freezers
What is vaccine efficacy?
The trials are blinded, meaning that neither the participant nor the study team knows whether a participant got the actual vaccine or a placebo (saltwater injection). Both are slated to last two years – meaning that participants are followed for two years to see if they develop confirmed COVID-19 and to look at their immune response to the vaccine. The trials are designed to be able to make vaccine efficacy estimates before the two-year mark. Vaccine efficacy is statistics – making predictions about how well the vaccine prevents illness based on numbers. After a certain number of events (COVID-19 illnesses) in the participants (deemed the endpoint), some statistical models are applied to determine how effective the vaccine might be. Based on these models, a certain number of cases among the participants, and how these cases are split amongst the vaccine and placebo group a certain percentage of efficacy can be calculated.
The trials are also designed for an independent monitoring board to take a “sneak peek” after a fewer number of cases. This is called an interim analysis. What we just learned about were these. Both trials had about 90 cases of COVID-19 in the participants and ~90% of these were in the placebo group, hence the greater than 90% efficacy estimate. While 90 cases do not seem like a lot in trials of 30,000-44,000 people, it is a lot for an event-driven vaccine trial. The primary endpoints are around ~150 cases, which based on current upticks in cases in the country should not take long to get to. While this seems like few, based on statistical modeling this is all we need to see if there is an efficacy over 60%.
What do we still not know?
The news was released by a press release, so no independent scientists have actually reviewed the data yet nor has the data been made public. Scientists, including myself, still have a lot of questions.
- How well does the vaccine prevent severe COVID-19? If the vaccine does not completely prevent illness altogether, is someone who is vaccinated less likely to need to be admitted to the hospital, need intensive care? We know this is the case for influenza vaccines. Moderna has said that 11 of the cases were severe and none of these were in the vaccine group – which is good news. Even if the vaccine does not prevent illness altogether but still prevents severe illness, it will greatly reduce the impact on our healthcare system.
- Does the vaccine prevent asymptomatic infection? We know that people can spread SARS-CoV-2 and never feel sick. It would be helpful to know if the vaccine prevents this, as it provides indirect protection to others. It is still possible to have a vaccine that prevents disease and illness but not an infection. Since the trial was primarily set up to look for illness as endpoints, this question may be harder to answer.
- How well does the vaccine work in the elderly and children? Both trials have participants over 65. There is some evidence to suggest that the elderly have weaker responses to vaccines, including the flu vaccine, and need a higher dose. The Pfizer trial is unique in that it includes children ages 12-18. This is so important because children may respond differently to the vaccine. It may take some time until the vaccine efficacy can be evaluated in children under 12.
- How long does any protection last? This is hard to know because only time can give us this answer. It is still too early to say if we will need to be vaccinated every year, need a booster every couple of years, or have lifelong immunity.
What’s next and when can we expect to get vaccinated?
The FDA has told us that they will not authorize a vaccine for use unless it shows at least 50% efficacy. The good news is that early data from both trials exceed this. The next step is for them to submit their data to the FDA for emergency use authorization (EUA). This does not mean full FDA approval but that given the circumstances, the FDA thinks the benefits outweigh the risks. This is still a very high bar. Thus, the FDA wants at least two months of safety data from the trial participants. Additionally, there will be systems in place to monitor any adverse events, should there be any, as people get vaccinated. As a Pfizer participant, I have seen first-hand that safety is the highest priority. Additionally, they must show that it can manufacture the vaccine consistently and with the highest quality standards. If the FDA gives EUA, you can be sure their experts think it’s safe.
If they have approval, there will be very limited doses at first. Many organizations and agencies have come up with early distribution plans. Healthcare professionals and first responders will likely be first followed by essential workers and those with the highest risk like those in congregate care facilities. The general public will likely not be able to be vaccinated until the spring of 2021. Until then it is so important to continue wearing a mask/face covering, practicing physical distancing, and not gathering in groups especially indoors. And be sure to get your flu shot!
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