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  • Writer's pictureRob Swanda, PhD

Are Two Shields Better Than One?

Updated: Apr 7, 2022

Words & Video by Dr. Rob Swanda

In the last few days of March 2022, the US Food and Drug Administration (FDA) announced eligibility for a second Covid-19 booster dose for those individuals who received the Pfizer/BioNTech, Moderna, or Johnson & Johnson initial vaccine series.

Chart 1 – US Covid-19 Second Booster Dose Eligibility as of 04.06.22
Chart 1 – US Covid-19 Second Booster Dose Eligibility as of 04.06.22

However, second booster doses appear to be limited to an individual receiving Pfizer/BioNTech or Moderna.

Chart 2 - Comparing Covid-19 First and Second Booster Dose Manufacturers as of 04.06.22
Chart 2 - Comparing Covid-19 First and Second Booster Dose Manufacturers as of 04.06.22

With the SARS-CoV-2 virus continuing to spread across the world and additional variants (including Omicron and the Omicron family of variants) emerging, our defenses still need to be raised to avoid illness, hospitalization, or death from Covid-19. Unfortunately, variant specific vaccines are not expected soon. Our only choice is to turn to the vaccines developed against the original strain of SARS-CoV-2, which have demonstrated to provide incredible protection in study after study after study. But our immune system does need consistent reminders of what the spike protein on SARS-CoV-2 looks like to be prepared to fight off an infection, especially during waves of heightened case numbers. This is where boosters come into play, and you can read more about why and how boosters are effective in my earlier blog (Covid-19 Boosters: The Shield to our Armor).

Recent studies have identified that mixing vaccine manufacturers provides the most promising effect regarding booster doses, especially when using mRNA type vaccines (Chart 2). Below I am venturing away from my typical writing style to break down the science of mixing vaccine manufacturers and provide my own hypotheses and rational for why this may be the case.

The mRNA vaccines for Covid-19 made by Pfizer/BioNTech and Moderna are very similar. They both allow our bodies to create the notorious spike protein, which our immune system responds to by creating antibodies & memory. As discussed last fall, switching between mRNA vaccines as boosters appears to be the most promising choice. My hypothesis is that since the mRNA sequence is essentially the same, the biggest difference comes from the LNP carrier (you can learn more about LNPs in my video here). The ionizable lipids for these formulas are under intellectual property, so they will each work a bit differently. This means some may have better or slightly different cell targeting than the other. So, by mixing the manufacturers we get as booster shots we are really building our immune response up for optimally targeted cells.

Additionally, even though I am an mRNA biochemist, I still greatly value the Adenovirus viral vector vaccines made by Johnson & Johnson and Oxford/AstraZeneca. Viral vector vaccines were a pivoting time in 2019 to create the first successful vaccine against Ebola. And then again in 2020/2021, used to immunize against Covid-19. But, using this technology as constant boosters I hypothesize their effect diminishing. This is because these vaccine types use a viral shell (as explained here) to deliver us genetic information about the SARS-CoV-2 spike protein. But, since our bodies can elicit an immune response to the carrier (viral shell / Adenovirus) itself, this could be problematic. This would not happen after one or two shots, but when we think of using them as boosters the immune response could attack the carrier before it has a chance to deliver the cargo, essentially forgoing any boosted affect to protect us from SARS-CoV-2.

Does this mean that everyone currently needs a second booster immediately? No. If you are in an environment where you have an increased risk of exposure or you have a medical condition that places you at increased risk of severe complications to Covid-19 then a second booster would be best obtained soon. But, as I mentioned earlier do not hold out for variant specific boosters to be coming soon. Governments are moving away from emergency use measures, which means timings with clinical trials & approvals are now longer compared to the timeline for the original Covid-19 vaccines.

As always, if in your location only one type of vaccine or booster is available, you should consider taking it. The best vaccine or booster is always likely to be that which is available. Additionally, if you are concerned about side effects from getting your vaccine you may decide to stick with the original manufacturer. For example, if you had no side effects from the Pfizer vaccine, then you may decide to continue with Pfizer as you are more familiar with how your body could react.

You should seek the advice of your physician(s) or other qualified healthcare provider(s) with any questions or concerns you may have regarding your circumstances, medical history, condition(s) and which vaccination may be best for your own unique personal situation.

Video: RNA Overview

Video: COVID-19 Booster Shots & Mixing Vaccines

Data sources:

The New England Journal of Medicine. (2022, 03 17). Homologous and Heterologous Covid-19 Booster Vaccinations. NEJM, 12 pages.

The New England Journal of Medicine. (2022, 03 09). Effect of mRNA Vaccine Boosters against SARS-CoV-2 Omicron Infection in Qatar. NEJM, 13 pages.

The New England Journal of Medicine. (2022, 03 16). Efficacy of a Fourth Dose of Covid-19 mRNA Vaccine against Omicron. NEJM, 13 pages.

The Lancet. (2021, 10 17). Effectiveness of heterologous ChAdOx1 nCoV-19 and mRNA prime-boost vaccination against symptomatic Covid-19 infection in Sweden: A nationwide cohort study. The Lancet, 7 pages.


Author: Rob Swanda, PhD of Title: Are Two Shields Better Than One? Date first published: 06 April 2022 Link:

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