Are we ready for a 4th COVID-19 booster? Absolutely not!

As we struggle in the United States to get even a minority of adults immunized with a third booster shot of the mRNA vaccines, a news story came out of Israel suggesting that they are essentially ready to begin to administer a fourth dose of the Pfizer vaccine.

Israeli Prime Minister Naftal Bennett (right) is briefed about Sheba Medical Center’s COVID-19 fourth shot trial on Tuesday, January 4, by hospital Director-General Prof. Yitshak Kreiss. from the Health Policy Watch.

One of my loyal readers was concerned about this “recommendation.” The concerns are warranted, and I have major issues about a press release on a study that isn’t even finished let alone unpublished!

First, however, I think it’s important to understand the function of the first three shots of the mRNA vaccines. The first dose of any vaccine is to initiate an immune response. It stimulates inflammation that “wakes up” the immune system to the vaccine antigen and then initiates the specific recognition by the immune system. The second dose, approximately three to four weeks after the initial shot, reinforces the immunity stimulated in the first shot giving it more intensity and longer persistence.

The third, or booster shot, has a very different function. It reawakens the immune response in a way that causes it to broaden and become much more long lived. Some vaccines that are given in three doses with a delay of 6 months have protection that lasts 10 to 20 years. A good example of this is the hepatitis B vaccine.

The reason that the third, booster dose protects more broadly against Omicron is because stimulating the immune response again six months after the initial response causes the immune response to expand and generates strong immune memory. There should be no need for another, quick booster.

The Israeli study therefore flies in the face of our general understanding of immunity and what we now understand about the COVID mRNA vaccines. If the third shot is truly a booster dose then we should not have to quickly give another shot. The protection should last a significant amount of time and should be broad enough to protect against other variants of SARS-CoV-2. 

In contrast, the Israeli report is focused on the concept that yet another dose of vaccine could produce neutralizing antibodies that would prevent COVID-19 infection. Most studies now show the mRNA vaccines (even with boosters) prevent disease and death, but allow for some breakthrough infections. Therefore, the point of the Israeli study, totally preventing infections by maintaining ultra-high levels of COVID antibody, seems incongruous with current knowledge.

Remarkably, the data presented in the press release does not show an impressive effect from this 4th immunization. There was only a 5-fold increase in antibody levels, much lower than the increases seen with prior boosters. Part of this may be that they were reporting the data only one week after administering the vaccine! They were also giving the vaccine to individuals who did not have a strong response to the first three doses.

Finally, there is data that indicates over-vaccination against persistent infections can potentially lead to immune exhaustion rather than immune protection. While I’m not suggesting that we’ve reached that point with the current COVID vaccines, after three vaccinations we must be circumspect about why and when we give any additional shots.

So lets not rush out for a 4th dose of COVID-19 vaccine based on a week long study of 150 people!

Published by jbakerjrblog

Immunologist, former Army MD, former head of allergy and clinical immunology at University of Michigan, vaccine developer and opinionated guy.

5 thoughts on “Are we ready for a 4th COVID-19 booster? Absolutely not!

  1. Dear Dr. Baker: Thanks a lot for this great blog! I read it regularly and found it extremely helpful. A quick question: do the rush to the 4th booster and recent surge of covid cases in Israel suggest that the 3rd dose is not truly a booster? Because otherwise as you said, it should provide protection that lasts for years.


  2. I would like to know if you have seen any studies on protection for those who had the J & J vaccine and then a booster MRNA. Is this as effective as 3 MRNA vaccines? Are suchbstudies being done? Thanks


  3. Do you believe there is still a role for a 4th mRNA vaccine in the immune compromised if they had some antibody response to the first three but not nearly that of a healthy person? Thanks!


    1. Yes, there may be some benefit but it has not been define as of yet. The real key is inducing cellular immunity. Without that all they antibody in a person won’t clear the virus.


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