Third Dose or Booster? Depends on Vaccine Versions and Variants

by Azra Behlim, PharmD

Vizient Associate Vice President, Pharmacy Sourcing & Program Services

Now that the federal government is recommending that many COVID-vaccinated Americans receive booster shots starting this fall, it’s important to know what a “booster” is and how it differs from a “third dose”.

There are three types of COVID vaccines that have been administered in the U.S. that are developed by different manufacturers and with different formulations and doses. As information is being reported in the media on these vaccines, it’s important to separate fact from fiction.

Variants: What’s the difference?

All viruses mutate over time. It’s part of evolution. When variant strains were first discovered of the COVID-19 virus, it was not a surprise to scientists. These variants at first were named based on where they were discovered, but over time it has become clear that these variants are also present in other countries. This created a new naming system to accurately track the spread of these variants going forward.

Vaccine booster: Do you need one?

The CDC issued guidance on August 18, 2021, that patients who were fully vaccinated with the Pfizer or Moderna COVID-19 vaccines may need a booster shot to maximize vaccine-induced protection and prolong its durability. The recommendation for a booster is for anyone who has been fully vaccinated for at least eight months or longer.

Vaccines typically provide their protection by activating multiple parts of the immune system.

One part is the production of antibodies, which helps to provide an immediate response to an infection. Another part is the activation of B cells and T cells which are part of the immune system’s “long term memory”. Activation of these cells is critical to providing a longer-term immunity against disease. With many vaccines, it’s the activation of these B cells and T cells that provide long-term immunity even when there are no detectable antibodies.

Johnson & Johnson and AstraZeneca are adenovirus-based vaccines. Adenovirus-based vaccines, such as the Ebola vaccine, typically provide immunity for at least one year or more.

Clinical trials by Pfizer and Moderna did not measure B cell or T cell activation and it is not being monitored in the ongoing mRNA trials. Therefore, it is unknown if the mRNA vaccines confer any long-term immunity.

Clinical trials by Johnson & Johnson and AstraZeneca for their respective COVID-19 vaccines measured a positive response by the long-term memory cells of the immune system. Ongoing trials continue to monitor this parameter to evaluate how long this effect will last.

Third dose vs booster

Is getting a third dose of a vaccine the same as getting a booster?  Maybe not.

A third dose is receiving the same formulation and same dose that was received in the first and second dose. This is currently recommended for immunocompromised patients as it is unlikely that a two-dose series in these patients would produce a sufficient immune response for adequate protection.

A booster shot is typically a smaller dose of the vaccine given to fully vaccinated patients after a period of time where immunity begins to wane. The purpose of a booster shot is to re-ignite the immune response to a higher level and does not replace the original two-dose series of vaccination.

Booster shots may also be reformulations of the original vaccination formulation. The first and second dose of the Moderna vaccine is 100 mcg. Moderna currently has three different formulations of a booster shot in a clinical trial. As data becomes available, the best candidate will be selected for the booster shot in the Fall of 2021.

At this time, for patients who received the Moderna vaccine and are immunocompromised, it is recommended they receive a full third dose of the Moderna vaccine and not a booster dose.

In the case of the Pfizer vaccine, the booster shot will be the same formulation and strength as the vaccine’s original two-dose series. Each shot is 30 mcg per dose.

There have been plenty of misunderstandings about the COVID virus that have spread, well, like a virus, through social media and other channels. It’s worth taking the effort to ensure we are all using the same language and using it accurately.  As data emerges to guide us in how to further prevent the spread of the virus, the public needs to clearly understand the vaccine options available to them and their respective differences. As we look to the future and continue to have more vaccines available, it is important that we continue to monitor the evolution of the SARs-CoV-2 virus, and the efficacy of our vaccines to stay one step ahead.