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Booster or Third Vaccine Dose: The Difference Between Them and the Issue for Pregnancy

There has been an increasing amount of discussion surrounding booster jabs, or third doses of COVID-19 vaccines, the discussions relating mostly to COVID-19 vaccines of Pfizer-BioNTech and Moderna. These are the mRNA vaccines and they are most relevant to the discussion, because they were both introduced as a two-shot (two-dose) series in contrast with the Johnson and Johnson (Janssen) vaccine that initially was introduced as a single dose. Moreover, because the mRNA vaccines are working very well and because of an extremely rare blood clot condition that affects women of reproductive age that may be connected with the Janssen vaccine and with the AstraZeneca/Oxford vaccine, women who received the initial dose of Janssen, or the initial two doses of AstraZeneca are being advanced to an mRNA vaccine for the next jab. Keep in mind, though that for the rest of the article, when we talk about a third shot it means a third shot for those who received any COVID-19 other than the Janssen. Now, the issue of ‘boosters’ or ‘third shots’ —we are about to define the difference between what those two terms mean— because you may have noticed a great number of headlines in the news suggesting that we have a booster problem, in that many people who are “fully vaccinated”, meaning that they have received the first two doses are not showing up to get boosted.

The idea that we are under-boosted is coming from a component of the public health expert community, exemplified by Dr. Eric Topol, a cardiologist who is Editor-in-Chief of Medscape and who spearheads the Scripps Translational Science Institute in San Diego. In many of the articles and media broadcasts built around the them that we have a problem, even though we have many people vaccinated with the two dose primary series, because we have a lot of people missing their third jabs, you often will see Dr. Topol quoted. In contrast, there are other experts saying that we should focus, even more, on getting jabs into the arms of people who haven’t received any jabs, and that a third shot, or booster, is not even necessary in young, healthy people. This perspective is exemplified by Dr. Paul Offit, Director of the Vaccine Education Center and Professor of Pediatrics at Children’s Hospital of Philadelphia/University of Pennsylvania, who has served on the Advisory Committee on Immunization Practices to the. Centers for Disease Control and Prevention.

To appreciate the difference between a ‘booster’ and a ‘third dose’, we need to discuss the purpose of the COVID-19 vaccines. That purpose, as with all vaccines against infectious disease, is to protect people against severe disease, the kind that can put them into the hospital, require admission to the intensive care unit (ICU) and cause death and long-term disability. This has been the purpose of the primary series, those two shots that you received. hopefully a while ago by now. Scientists studying the issue have found out that in people with healthy immune systems, those two jabs provide the immune system with target practice in such a way that the person builds of what immunologists call memory B cells and memory T cells. This allows the immune system to respond to an infection with SARS-CoV2 (the virus that causes COVID-19 well enough to prevent the virus from causing severe disease, or even moderate disease. While the two shot primary series appears to be enough to get to this point in young, healthy people, there are come caveats. First of all, it is not enough in people with what doctors call comorbidities, meaning health conditions other than COVID-19. In the case of COVID-19, such particularly high risk comorbidities include obesity or being overweight (BMI 25 or higher), heart failure, type 2 diabetes, and anything that weakens the immune system, including medications that blunt immunity. In such people, the two jabs are not enough for long-lasting memory cells, so they need at least a third jab, and it is called a third jab, because it’s really part of the process of getting the immune system up to speed to protect against the virus causing severe disease. There are people who are a fourth shot for the same reason. These shots are not called boosters. They are called third or fourth doses.

Now, while the presence of adequate amounts of memory cells is good long-term protection against severe COVID-19 and death, this alone will not necessarily prevent you from developing a mild case of COVID-19, particularly when it comes to the extremely contagious Omicron variant of the virus. But there is also another kind of protection that you develop, that can help against mild disease. This protection results from what immunologists called neutralizing antibodies. You build up neutralizing antibodies 2-3 weeks after your first jab. You build up a lot more neutralizing antibodies 2-3 weeks after your second jab. Thus, by 3 weeks after your second jab, if you have a healthy immune system, you have very good protection, even against mild COVID-19, although even then, because of Omicron, it is still possible to get sick. And remember, when we say a ‘mild’ case, this does not mean that you won’t feel horrible, but it does mean that you are not likely to need hospitalization. Now the problem with neutralizing antibodies is that the concentration of these antibodies circulating through your body wanes over time, and so a few months after that second jab, the numbers are a lot lower, so it is a lot easier to develop a mild case of COVID-19, if you are exposed to the virus.

A ‘booster’ jab is a dose of the vaccine that will boost your circulating neutralizing antibodies up. There is a possibility that there is also a benefit to the memory cells, only because there have been some studies suggesting that the immunity would be better if the interval between the first two jabs had been longer than four weeks, that expanding that interval to eight or especially twelve weeks would produce even better immunity. So, in a way, even though the booster is to boost up neutralizing antibodies to decrease the chance of getting even mild disease, or lessening the impact of an infection, it’s possible that scientists will find that the boosters have compensated for the fairly short spacing between the first two shots.

But here is the rub. While it is really nice to have added protection against the virus as a result of the booster jab, the effect on the level of neutralizing antibodies is temporary, just like with the second jab. And so, a few months after that booster, your level of neutralizing antibodies has dropped down and continues to drop. Getting another booster, say four months or so after the previous one will boost up the protection once again, but there are now studies from Israel, where a lot of fourth doses have been administered, suggesting that there are diminishing returns, if one keeps getting boosters every few months. We don’t do this with all of the other infectious diseases against which we have been immunized. Rather, we boost from time to time, according to schedules that have been devised based on the risk and disease and other factors, such as the person’s age and occupation. If we kept boosting vaccines every few months for every disease, our blood would become very viscous, because of very high numbers of circulating plasma cells, which are special B lymphocytes that carry antibodies. Additionally, there is another concern that immunologists call the original antigenic sin hypothesis. In a nutshell, the ideas is that, if we keep boosting immunity against the particular variant of SARS-CoV2 that was causing disease two years ago —which is the variant that’s the basis of the current, approved COVID-19 vaccines— then we’re training the immune system to be too focused on that variant. This could be problematic, not just just in the current omicron variant situation, but especially for future variants.

Now this brings us to the case of pregnancy, which in previous posts we have explained is a risk factor for the development of severe COVID-19, even if you are otherwise completely healthy, meaning no ‘co-morbidities’. The question becomes where does pregnancy fit in with respect to immunity? In a way, it is kind of like getting older. The immune response may be slightly less robust, in which case we might think of a booster as being a little like a third shot of the primary series, that it is reasonable to consider it a factor that would reduce your risk. So, while weighing the benefits against the disadvantages might lead a non-pregnant healthy woman below the age of 50 to opt against a booster, based on the disadvantage being that she might feel ill (fever, chills, body aches) for a day or two after the jab, being pregnant (or planning to become pregnant) should be a factor pushing you toward getting that booster.

David Warmflash
Dr. David Warmflash is a science communicator and physician with a research background in astrobiology and space medicine. He has completed research fellowships at NASA Johnson Space Center, the University of Pennsylvania, and Brandeis University. Since 2002, he has been collaborating with The Planetary Society on experiments helping us to understand the effects of deep space radiation on life forms, and since 2011 has worked nearly full time in medical writing and science journalism. His focus area includes the emergence of new biotechnologies and their impact on biomedicine, public health, and society.

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