By Rachel Levene, PhD Candidate in Molecular Microbiology at Tufts University School of Medicine and daughter of Dr. Eric Levene, Chester Pediatrics.
Almost 1 year ago our lives were dramatically upended by the COVID-19 pandemic. We quickly adjusted to a new virtual world as we frantically ran to the supermarket to make sure we had two weeks’ worth of essentials. We clapped each night to solute frontline responders all while hoping we would soon have effective vaccines to return our lives to normal.
In one year, it’s a massive scientific achievement to have not just 1, but 3 highly effective and safe vaccines against COVID-19: Pfizer-BioNTech, Moderna, and Janssen/Johnson & Johnson. With three different vaccines, I’m here to explain how these vaccines work and why the best vaccine is the one you can get in your arm as soon as possible.
Pfizer-BioNTech and Moderna
Pfizer-BioNTech and Moderna’s vaccines are very similar – they are both mRNA vaccines. The central dogma of biology is that DNA makes mRNA and mRNA then make proteins. These vaccines are the mRNA message for a portion of the Spike protein. Spike is a protein on the surface of the SARS-CoV-2 virus that allows it to attach to our cells and infect them. After a person is injected with these vaccines, the muscle cells in their arm begin to make Spike proteins (it cannot give you COVID because the virus needs all its proteins, not just Spike, to cause infection). Since these proteins are not “normal” proteins produced by cells, the immune system recognizes them and makes antibodies against Spike. The immune system is being “tricked” into thinking COVID-19 is present. After the Spike proteins are made and antibodies recognize them, the mRNA from the vaccine and Spike proteins are chewed up by the cell as waste. The antibodies remain and the goal is that the next time the immune system “sees” Spike, like during an infection, we can respond and destroy the virus before it can replicate and cause damage. We need two doses of both of these vaccines, called a prime-boost, to make sure the immune response is robust and durable enough. The “boost” serves to enhance the immune response from the first dose since early studies showed one dose did not provide a strong enough immune response.
After 2 doses, both of these vaccines are ~95% effective and preventing symptomatic COVID-19 illness, and almost ~100% effective at preventing hospitalization and death. “Real-world” data from a study in Israel corroborated these results for the Pfizer-BioNTech vaccine.
These vaccines have some logistical drawbacks –they both require storage in freezers and require people to come back for a second dose. Thus, we need twice as many doses to fully protect everyone. Additionally, these vaccines frequently have some side effects, which may discourage people from taking them. However, these side effects are mild (sore arm, fatigue, headache, etc) and transient and should not discourage you from taking them if they are available to you. The side effects are the result of the immune system revving up and responding to the vaccine.
Janssen/Johnson & Johnson
Janssen/Johnson & Johnson vaccine is different from that of Pfizer-BioNTech/Modern – it uses an Adenovirus vector. Adenoviruses are viruses that normally cause colds. The viruses are good at getting into our cells making them a good way to “deliver” information to the cell. Just like Pfizer-BioNTech/Modern, this vaccine delivers the message for the cell to make Spike. Instead of delivering it in mRNA form, it delivers it in DNA form. The adenovirus has been “disarmed,” or stripped of all the information it needs to cause a cold and instead just holds the message for Spike. Because of this, it cannot replicate. It is simply a vessel or vector for delivering the Spike message. Upon injection, the “virus” enters the cell and the DNA encoding Spike is transcribed into mRNA and the mRNA translated into the Spike protein. Because these Spike proteins are not normal cellular proteins, our immune system recognizes them as foreign and makes antibodies against them. We are tricking the immune system into making a response to COVID-19 without ever having COVID-19. The benefit of immunity is achieved without the risks of infection and illness. After antibodies are made, the DNA, mRNA, and Spike proteins are also chewed up by the cell as waste. This vaccine is based on the same principle as Pfizer-BioNTech/Moderna but just starts the process one step earlier.
After 1 dose, this vaccine is ~72% effective at preventing symptomatic COVID-19 illness, and almost 100% at preventing hospitalization and death. This is amazing and for comparison, the flu vaccine is only 40-60% effective at preventing symptomatic influenza, depending on the year.
While 72% is lower than the 95% efficacy of Pfizer-BioNTech/Moderna, it is important to know that we cannot directly compare them. For starters, the trials largely collected a bulk of their data at different times. Pfizer-BioNTech/Moderna was largely done before the start of the winter surge and the emergence of variants and a majority of their data came from the US. That said, J&J collected a bulk of their trial data during the winter surge, amongst the variants, and around the world. Thus, the “reduced” efficacy maybe because of variants that emerged that may “escape” vaccine-induced immunity. Vaccine escape is caused by the mistakes or “mutations” in the viral genome that cause Spike to slightly change its shape so that it can no longer be recognized by the antibodies made in response to the vaccine. It’s like trying to put a square peg in a round hole – it does not fit. With that said, a square peg can partially contact areas of the round hole and the current vaccines can likely offer some degree of protection against the escape variants.
In the clinical trial, this vaccine had less frequency of side effects compared to Pfizer-BioNtech/Moderna. The side effects are not dangerous and exactly what we might expect after vaccination — sore arm, fatigue, headache, etc.
One advantage of the J&J vaccine is that they presented some data to the FDA showing that vaccinated individuals are less likely to transmit the virus. This is huge because it offers protection to those around vaccinated individuals. It is likely the Pfizer-BioNTech/Moderna vaccines will also do the same, we just do not have a large amount of data supporting this yet. Additionally, J&J presented data from the trial showing that vaccinated individuals who became sick had decreased intensity of symptoms.
Another huge advantage of the J&J vaccine is that it only requires refrigeration rather than a freezer and it is 1 shot. Thus, more people can get fully vaccinated more quickly and we can more quickly achieve herd immunity and return to a sense of normalcy.
Which vaccine should I get?
The first one you get can get is the best vaccine. All three vaccines are safe and effective at preventing severe illness, which is what we care about most since it overwhelms the hospitals. If I was not already vaccinated as part of the Pfizer-BioNTech trial, I would happily take the J&J vaccine.
As Dr. Fauci and our public health experts have said, we are currently in a race to a vaccine to prevent the vaccine escape variants from taking hold. Viruses cannot mutate or change if they cannot replicate. We need to vaccinate as many people as possible to prevent the emergence of more variants, prevent existing variants from taking hold, and protect the most vulnerable.
Until we have large-scale data showing that these vaccines entirely prevent asymptomatic infection/transmission it is critically important to continue wearing a mask, even if you are vaccinated. With vaccinations and masks, we can significantly reduce the levels of virus circulating and potentially have a “normal” summer.
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