Third Shots and Boosters Against COVID-19 – What You Need to Know

With record-breaking numbers of new cases, it’s time for everyone to get their first, second and third jabs.

Why do I need a booster?

The fourth wave is upon us. In Austria, on November 10th, we had a staggering 11,398 new cases, our highest number since the pandemic began. 

We have almost a year of experience with COVID-19 vaccines, and the data are in – the RNA vaccines from Pfizer/BioNTech and Moderna are highly effective at protecting people from hospitalization and death. But, protection doesn’t last forever. 

Antibodies after vaccine-induced immunity and natural infection gradually wear off. Two doses of the Pfizer/BioNTech, Moderna and Oxford/AstraZeneca vaccines lose effectiveness within months. Even more concerning are breakthrough infections with the delta variant, despite seemingly adequate levels of neutralizing antibodies.  

Waning immunity combined with new variants means that two doses of the vaccine are not enough for most people. We need boosters to fend off COVID-19.

What’s the difference between a booster and a third vaccine? 

The terms are generally interchangeable. But, there is a distinction. Typically, a person receives a booster shot to extend immunity when protection from the original shots starts to wane. In contrast, an additional or third dose is usually for people who never made a protective response in the first place – especially in people who are immunocompromised.

How effective is the third dose?

A booster or third dose should protect against breakthrough severe and life-threatening infections in people with reduced antibody levels and those who did not respond to their initial vaccines. 

So far, the studies show that vaccinated people have far fewer deaths with two doses and appear to improve with three vaccines doses. 

Support for a booster comes from an early study in Israel that found that fully vaccinated people over 60 who had a booster five months after their second vaccine were less likely to be infected with COVID-19 and were unlikely to develop severe illness ( In other studies, researchers found that a booster with Pfizer or Moderna vaccines significantly increased the vaccine’s efficacy.

Which one should I take?

Whichever vaccine you received, it’s safe to receive a COVID-19 booster or additional dose that differs from your initial dose or doses. But if you’ve received two Pfizer-BioNTech or Moderna COVID-19 vaccines, it’s probably better to have the same one for your booster. The Pfizer and Moderna vaccines are similar, but immunity from Moderna seems to take a bit longer to wear off. 

What about mixing and matching? The data suggest that vaccinating with different types of vaccines improve immunity. The reason is that the two types stimulate different arms of the immune system and will potentially provide a broader immune response. So, if you’ve had two AstraZeneca vaccinations, then either RNA vaccine will be okay. 

If you’ve had COVID-19, you also need to get two vaccines and a booster because fully vaccinated people are better protected than having natural infection with SARS-CoV-2 (). Mixing and matching vaccines in previously infected people is also fine.

What dose should I take?  

The Moderna vaccine dose contains 100 mg compared to 30 mg in the Pfizer vaccine. For the booster, the Pfizer vaccine is the same as the first two. For the Moderna vaccine, the recommendation is for half a dose, which in studies is protective and has the added benefit of fewer side effects. 

When should I take it? 

Ideally, testing antibody levels would be necessary to determine if they need a third dose. But we don’t yet know which antibody is most predictive of an excellent protective response, and it’s costly. Also, we already know that in the majority of people antibody levels reduce over months Studies comparing people vaccinated in January, April and June for antibody levels and breakthrough infections are underway but are complicated because of the arrival of the delta variant. In other words, a breakthrough infection could happen because of lower immunity or because the vaccine is less effective against a new variant. 

The recommendation is to have a booster about half a year after the last vaccine. Here in Austria, the strategy is to give boosters four months after two AstraZeneca vaccines and six months after either Pfizer or Moderna vaccines. 

How long will booster immunity last?

This is hard to say, because It depends on so many factors, starting with your immunity level after a COVID-19 infection and/or the first two vaccines. After that, it depends on how fast your antibodies (I took out T lymphocytes, because they don’t dissipate, it’s okay to include just antibodies) dissipated over time. And then, there’s always the effectiveness of your immune responses against viral variants. 

With breakthrough infections following a booster, we don’t yet know enough..

Are there risks associated with a third dose? 

There are mild to moderate side effects after the third mRNA dose, similar to the initial doses. Some people experience no side effects, and others may have fatigue, headaches, fever, muscle aches, or pain at injection. 

Some pundits suggest that boosters could decrease immunity by inducing inhibitory antibodies, which would make the vaccine ineffective. But there is as yet no proof for this assertion. 

However, more than three vaccines in a relatively short time, say within a year, could have unexpected consequences and should be avoided.

Will I need more in the future? 

As we do for influenza, we will likely require updated vaccines that recognize variants and maintain protective antibody levels. 

But we can reduce the need by decreasing the chance of the virus mutating. But for this, we need to vaccinate everyone and boost immunity in immunocompromised people. New variants arise primarily from the unvaccinated and the immune-compromised: For example, anyone on chemotherapy or immune-suppressors – as after organ or stem cell transplants – has a primary immunodeficiency, as does anyone with HIV, or who takes high-dose steroids or other immunosuppressive medications.

Even if fully vaccinated, immunocompromised patients risk breakthrough infections, hospitalization with severe COVID-19 and an increased chance for the virus to mutate, often into a more contagious and deadlier variant that we can’t fight off. 

So while the third dose is effective now, a novel variant could still appear that isn’t covered by the current vaccines, and then we’ll see more breakthrough infections. We must continue monitoring for new variants, testing them against antibodies generated by the current vaccines, and producing boosters against them. 

In the meantime, we still need to keep safe by reducing exposure to COVID-19 infection, by wearing masks, washing our hands, and avoiding touching our faces. It feels like back to square one; but for now, we have little choice. 

Dr. Michelle Epstein
Michelle Epstein is a medical doctor graduated from the University of Alberta in Canada, who has specialised in Internal Medicine at the University of British Columbia and Allergy and Clinical Immunology at Yale University. Since 2004, she has been a Lab Leader at the Medical University of Vienna’s Division of Immunology.

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