In a previous post about when we might expect an effective vaccine for SARS-COV-2, I said it would be unlikely that a vaccine would complete phase 3 trials and be approved by early 2021. I love being wrong about that prediction! There are three vaccines that have been shown to be highly effective in phase 3 trials, and at least two of them are likely to be approved before the end of 2020. The third one will likely be approved within the next month or two. Each vaccine requires two doses and each has certain advantages and disadvantages. I will briefly describe those for each of the three vaccines below.
Pfizer-BioNtech vaccine
This vaccine was developed by a collaboration between a U.S. pharmaceutical company, Pfizer, and a German biotech company, BioNtech. It uses a technology that has never been used in a licensed vaccine before called mRNA (messenger RNA).
Traditional vaccines require growing the virus in tissue culture and then breaking down the virus into components that will stimulate the immune system to make antibodies. It is a very labor intensive process to make these viral components, and they have to be intensely purified to make them safe and effective.
Messenger RNA that codes for certain SARS-COV-2 proteins can be chemically synthesized in large quantities. When injected into the upper arm, these mRNA molecules are absorbed into muscle cells, and then the muscle cells begin to make the SARS-COV-2 spike proteins. The immune system recognizes these as foreign invaders and develops antibodies against them. The genius of this approach is that the body manufactures the viral components itself rather than the labor intensive process for traditional vaccines.
One problem with this approach is that mRNA molecules are very fragile and easily fall apart. The Pfizer-BioNtech vaccine must be stored at -94 degrees. This requires a special freezer. It will be a challenge to distribute this vaccine to a large number of people, particularly in the developing world where such freezers are expensive and unavailable
Data from phase 3 trials show an efficacy of 90%. That means that that there were nine infections in the people who got the placebo vaccine for every one infection in the people who got the real vaccine. That is extraordinary. The flu vaccine, for example has only about 50% efficacy.
Moderna vaccine
This vaccine was developed by a U.S. pharmaceutical company based in Massachusetts. It is also an mRNA vaccine and also has an efficacy of 90%. Moderna used a special trick to avoid having to use super cold storage required by the Pfizer-BioNtech vaccine. They enclosed the mRNA molecules inside little lipid (fat) membranes. This makes the Moderna vaccine more stable so that it can be stored at normal freezer temperatures of zero degrees.
Oxford-AstraZeneca vaccine
This vaccine was developed by the British pharmaceutical company, Oxford and will be manufactured by the U.S. pharmaceutical company, AstraZeneca. Rather than injecting mRNA directly, the company used a cold virus isolated from Chimpanzees. They deleted 20% of the virus DNA, so that it is unable to reproduce inside the human body. They replaced that 20% with genes that manufacture the SARS-COV-2 spike protein. The virus enters the human cells and then the cells manufacture the spike protein. Once again, the immune system recognizes this spike protein as a foreign invader and makes antibodies against it.
The efficacy data for this vaccine is a little puzzling. Because of a manufacturing error, AstraZeneca made some vials that contained only a half dose of the vaccine. People who got the half dose first and then the full dose for the second shot showed a higher efficacy (90%) than those who got two full doses (70%). Moderna and AstraZeneca will have to add more people to their phase 3 trial to resolve this issue. This will delay the application for approval by a month or two. A huge advantage of this vaccine is that it can be stored at refrigerator temperatures.
Side Effects
Side effects in the phase 3 trials were not common, but did include fever, muscle aching, headache and fatigue. These symptoms only lasted a day or two and then resolved completely. There have been no serious or long term side effects reported with any of the three vaccines.
Length of Protection
Because this a novel virus that has been circulating in humans for less than a year, we do not know how long immunity will last. Hopefully it will be at least a year, but at this point that is unknown.
Will vaccines keep me from getting infected and passing the virus on to others?
The only thing that was tested in the phase 3 trials was prevention of symptomatic illness. It is possible that vaccinated people are still susceptible to asymptomatic infection and might still transmit the virus to others. Until this question can be answered, people who receive the vaccine should still practice masking and social distancing.
When will these vaccines be available?
The logistical challenge of manufacturing and distributing any of these vaccines will be daunting. None of these vaccines will likely be available to the general public before this spring or summer.
Should I take a vaccine when it is available and which one?
All three of these vaccines have had rigorous evaluation for efficacy and safety, and the FDA will review all these data independently before approving them. I would strongly recommend taking any of these vaccines once they are approved by the FDA. I certainly intend to do so,