In this two part series, we will discuss passive immunity and how this creates a dilemma if you are pregnant, healthy, and already have received several vaccine doses against SARS-CoV2 (the virus that causes COVID-19). In this first part, I’ll provide some background, which will set us up to talk about the booster dilemma.
In general medicine, you have heard about it in the context of COVID-19 and monoclonal antibodies (mAbs). In people who are immunocompromised, due to certain medical conditions, or medications that they are taking, the vaccines against SARS-CoV2 (the virus that causes COVID-19) don’t work as well as they do in young to middle-aged healthy people. They need more booster doses than other people need and still the immunity is not up to speed. And so, if they do become infected and develop a mildly symptomatic case of COVID-19, they are at risk of developing severe COVID-19. Antiviral medications, like ritonavir-boosted nirmatrelvir (Paxlovid) and remdesivir can be helpful, but also doctors have been treating such people with mAbs, designed specially to work against SARS-CoV2, by companies, such as Eli Lilly, Glaxo SmithKline, and Regeneron.
Unfortunately, the effectiveness of such mAb treatments has been waning, due to the virus evolving to evade these antibodies. Given our topic for today, it’s worth mentioning that evolving resistance is something that, fortunately, has not been happening when it comes to COVID-19 vaccines. While researchers are currently working on new mAbs, I have opened this post by mentioning the topic, because it is an example of passive immunity. The mAbs are infused into the patient’s blood, where they fight against the virus for a few months. It’s a temporary effect because the antibodies are not made the recipient. They’re administered into the blood, where they have a certain half-life, a certain amount of time over which their concentration is cut in half. After a few half-lives, they’re not helping much anymore, so the person needs a new infusion.
Similarly, when you as a pregnant woman make antibodies, your fetus can receive the antibodies through the placenta, and so becomes passively immunized just like the person who receives an engineered mAb. It’s only a certain flavor of antibodies that transmits from maternal to fetal blood vessels in the placenta. That flavor is immunoglobulin G (IgG), which is one particular component of the immune response to a particular antigen, such as the segment of the spike protein of SARS-CoV2 that vaccination with an mRNA vaccine causes certain cells to present to the immune system inside lymph nodes. In referring to the mRNA vaccines, we mean the vaccines of Pfizer-BioNTech and Moderna. On first exposure to an antigen, most of the antibodies made are of the IgM flavor. These do not pass to the fetus, because they travel in the blood in groups of five, so they are too big. But IgG is the ticket to passive immunity imparted to the fetus while you are pregnant.
I have brought up the topic of passive immunity because every time you receive a booster shot against SARS-CoV2, you generate a spike in the concentration of IgG antibodies against the virus. That’s good for your baby, particularly if you time things so that the spike in antibody levels comes just before the baby is born. That way, the passive immunity will last for most of the first year of the baby’s life.
When it comes to your own immunity, however, here is where booster jabs start to create a dilemma. The dilemma derives from the fact that IgG is the only component of immunity that you transmit through the placenta. You do not transmit what immunologists call T-cell immunity. This is immunity that works through special immune cells called T-lymphocytes. You also do not transmit what are called memory B lymphocytes to the fetus.
While there has been a lot of messaging from health authorities saying that you have one of the updated boosters, and that you can have such a booster as soon as two months after your most recent booster, this is really the result of a decision to keep things very simple for the public. Telling everybody to get as many booster shots as is permitted will maximize the number of people who get immunized and the amount of immunity that exists in the population. But, as we have discussed previously, the reality of boosting is much more complicated. The vaccines against SARS-CoV2 are examples of amazing biotechnology. They are a great success story of our era, including the vaccines that work with the mRNA platform (Pfizer-BioNTech and Moderna). But scientists did not create these wonderful vaccines for people to get boosted continuously every 2-6 months to keep their levels of neutralizing antibodies as high as possible, thus maximizing protection even against mild cases of COVID-19. Instead, the purpose was to keep people from dying of COVID-19 and to keep intensive care units from being overwhelmed, as they were before the vaccines became available. This means protection against the virus penetrating into cells of the lower respiratory tract and spreading throughout the body, a process that involves the virus attaching to a protein on body cells, called the ACE-2 receptor. Interacting with ACE-2 is what leads to severe complications that kill people, like acute respiratory distress syndrome (ARDS).
What the vaccines appear to be very good at doing is preventing the virus from being able to penetrate those deep areas of the body, particularly the lower respiratory tract. Scientists think that this must have a lot to do with T lymphocytes and that memory T lymphocytes and memory B lymphocytes preserve the capability. In contrast with levels of neutralizing antibodies —which fade over a few months and which gave many journalists the idea that the vaccines have been losing their effectiveness— memory B cells and T cell immunity appears to be lasting. Studies have told scientists that this kind of immunity against SARS-CoV2 is not deteriorating much at all in people who have received three doses of a vaccine.
In part 2, we’ll jump into the issue of the fourth dose, in the United States as of the writing of this in late January 2023 means the bivalent Omicron booster that was approved September 1, 2022.