COVID-19: Booster Doses – Part 2

In Booster Doses – Part 1 I wrote about some of the basics of booster doses and the need for “additional” doses (not booster doses) in patients with compromised immune systems. Today I’m going to talk about some of the rationale behind booster doses in patients with healthy immune systems.

At the bottom of this post is a list of some background posts and definitions that may be useful.

What about people with healthy immune systems? I hear booster doses are coming for them. Why is that?

First let me list those things that are NOT reasons for booster doses. Please see this post and this post for more elaboration on the points below.

1. The vaccines are still highly effective. 
2. Vaccinated people are still very unlikely to have severe disease from COVID-19.
3. The vaccines are still effective against the variants, including the Delta variant.

There are three main reasons why booster doses are coming:

1. Both Pfizer and the CDC report a slight reduction in vaccine effectiveness against COVID-19 disease as time elapsed since the second dose. Pfizer reported effectiveness went from 95% to 84% and the CDC report stated effectiveness went from 92% to 80% over the past six months or so. These are relatively modest reductions in effectiveness that I do not find worrisome.
2. The CDC has presented data that the quantity of antibodies decreases and the percent of patients without detectable antibodies increases over time after the second dose of the Pfizer and Moderna vaccines. 
3. The CDC released a report on August,18, 2021, from New York nursing homes showing a reduction in effectiveness from 75% in March through May to 53% in June through July. This could be due to the Delta variant, but I think the reduction in effectiveness is more likely due to a reduction in circulating antibodies coupled with the fact that nursing home residents are more likely to have suboptimal immune systems to begin with.

So people who were vaccinated with a Pfizer or Moderna vaccine will soon not be protected?

No, that’s not the case. Vaccine-induced immunity is a complex web of variables. So bear with me while I try to simplify things.

The running assumption, which I think is valid, is that antibodies play a key role — and possibly the most important role — in protecting against COVID-19 infection. That sounds simple enough, but remember that you need to have the right number and type of antibodies in the right place, at the right time.

In the case of COVID-19 this means you have to have sufficient concentrations of neutralizing antibodies in the respiratory mucosa, and the antibodies need to get there fast enough to protect against the virus. That sounds easy enough except that we can’t easily measure antibody concentration in the lungs; we can only measure antibodies in the blood. In addition, we don’t know the exact ratio (or if one even exists) between concentration in the respiratory mucosa and the concentration in the blood. And even if we knew that ratio, we don’t know the concentration of antibodies needed in the respiratory mucosa to prevent infection. 

We have an idea of what concentration of antibodies in the blood correlates with protection, but there is probably some variability between people. It’s possible that younger, healthier people are able to prevent infection with lower antibody concentrations than those who are older or less healthy.

Another key point is that different concentrations may suffice for different purposes. For example, a relatively low concentration of antibodies may be more than adequate to prevent severe disease, but not enough to prevent infection or more mild disease.

And it gets even more complex because we know with many other diseases that even the complete absence of antibodies in a vaccinated person’s blood does not necessarily mean lack of protection. This is because of a “memory” response. 

We have good evidence that the mRNA vaccines (and likely the adenovirus-based vaccines as well) produce a “memory” response using B-cells and helper T-cells. This immunologic memory means that if your body is exposed to an antigen, it “remembers” that invader, and then it can start producing antibodies again to help defend against the invader. 

For diseases that replicate primarily in the blood and have long incubation periods (e.g. measles, hepatitis B), the body usually can produce antibodies fast enough to prevent infection. But producing antibodies from scratch and getting them to your respiratory tract in less than five days (the average incubation period of COVID-19) is probably difficult for the immune system.

There is likely more than enough time, however, for a vaccinated immune system to ramp up a response that is protective against severe disease (as opposed to mild or asymptomatic infection), because the response needed to prevent severe disease doesn’t need to be as great or as fast as that needed to prevent infection.

And, of course, time plays another key role. As more time elapses since a person’s last exposure to an antigen (either due to infection or its immunologic doppelganger, vaccination), your immune system figures it no longer needs to produce antibodies all the time so it sort of turns off the spigot. As I describe above, turning that spigot back on takes time.

What will the CDC recommend concerning booster doses?

News reports state that the CDC will recommend next week (likely on August 24, 2021) that individuals previously vaccinated with an mRNA vaccine (Pfizer or Moderna) should receive a booster dose at least eight months after their second dose, and that administration of booster doses will start on September 20.

So the mRNA vaccines are only effective for eight months?

NO! That is absolutely the WRONG conclusion.

The most accurate conclusion is that the number of antibodies circulating in the blood after the second dose decreases over time, such that by about six to eight months after the second dose there is an increasing likelihood that there are no longer antibodies present. Your body can still produce such antibodies, if prompted to do so, however. Therefore, in an attempt to maximize possible protection against this nasty virus, we will do the logical thing and give a booster dose.

This does NOT mean that antibodies will drop eight months after receiving a third dose. Instead it is quite possible that the immune system will generate antibodies that last longer after a third dose than those antibodies produced after only two doses. 

Why? Well remember what I wrote above about your body turning off the immunity spigot if it doesn’t see the invader for a while. The body may need three doses before it starts realizing, “Oh, you mean I’m going to see this invader a lot? Ooooh, ok, well in that case I’ll just leave the spigot on and shift into cruise control.” (That is the weirdest mixed metaphor I’ve ever written).

Why the eight-month interval from the second dose of the vaccine series?

First of all, I think the reason for the eight month “rule” is far more practical than scientific in nature. See, eight months from the first dose isn’t standard timing for vaccine series. Far more common would be something like six months after the first dose. 

Usually the interval between the first and second dose of a vaccine is about one to two months. Both Pfizer and Moderna chose their intervals not because 21 days (for Pfizer) or 28 days (for Moderna) is clearly the right one. They were picking intervals that made immunologic sense. My hunch is that Pfizer went with 21 days to try and get a full series done in as short an amount of time as possible.  

So the “regular” way many immunizations are scheduled is something like zero, one and six months. Where the first dose is called time zero, the second dose is one month after the first dose, and the third dose is six months after the first dose (five months after the second).

Much, but not all, of the data about the immune response of COVID-19 vaccines is taken over a six-month time period. But if six months from the second dose were made “the rule,” we’d have a lot of patients due for the booster dose right off the bat.

If you take the reported date of September 20 of booster dose administration as accurate, and you work back eight months, you end up pretty close to the date when the first batch of vaccinated patients would have finished their vaccine series. Which means you end up having a steadier stream of booster doses needed, rather than a huge number right from the get go.

For those of you, like me, who were lucky enough to be vaccinated early, in December 2020 or January 2021, don’t panic about the specifics of when you’re “due.” 

First of all, the great thing about vaccines that produce a memory response is that you can’t be “too late.” You don’t have to restart the whole series. If you end up being nine months after your second dose, just get your booster. By the way, that rule works for pretty much any vaccine. Rarely, if ever, does someone have to restart a vaccine series.

Second of all, the available evidence indicates that most vaccinated people still have high levels of protection, certainly against severe disease. So don’t sweat the details. Just go get your booster when they’re available. 

Tomorrow Part 3 of this series will go into some more specifics about the upcoming booster doses.

Stay safe, and go make some lemonade.

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Past reading and definitions that may be helpful:

Please read this post for a somewhat in-depth description of how immunity prevents infection, disease, and contagiousness.

Please see this post to review some basic definitions. I’ve also pasted that list below along with some new definitions. (If you already know or remember these definitions, just skip to the next heading.)

COVID-19 infection. This is defined as, uh, well, infection with COVID-19. (You subscribe to this blog for that level of analysis, right?) This definition includes people who have “disease” as well as people with no symptoms.

Asymptomatic infection. People who are infected but who do not develop symptoms.

Incubation period. The average time from infection to onset of symptoms. For COVID-19 the average incubation period is about 5 days.

COVID-19 disease. A patient who is infected with COVID-19 and has symptoms of that infection (including anything from a low-grade fever all the way to severe pneumonia requiring mechanical ventilation).

Severe COVID-19 disease. There is no strict definition of the word “severe.” Obviously being hospitalized is an example of severe disease, and just having a minor cough is not severe. For purposes of this discussion, it is best not to quibble about definitions and use the term “severe” in its standard English meaning.

Infectious. A person who can spread COVID-19 to other people. Both those with asymptomatic infection and those with COVID-19 disease are infectious and can spread the virus. In general, people who never develop symptoms appear to be less infectious than those who eventually develop symptoms.

Carriers. We don’t really have COVID-19 “carriers.” A carrier usually refers to someone who is infected with a microorganism and carries that organism in their body for an extended period of time, like months. Bacteria provide the best example of “carriage.” Although we don’t know how long patients who have asymptomatic infection with COVID-19 have viable virus in their respiratory tract (and are therefore contagious), it’s probably no more than 10-14 days.

Antigen. The part of a virus or bacteria that causes your body to generate an immune response. Not all antigens are proteins, but many of the best ones are.

Antibody. A protein produced by the body that attacks pathogens like bacteria and viruses. Antibodies are produced either in response to infection or immunization.

Neutralizing antibodies. Antibodies that neutralize a pathogen (didn’t see that one coming, did ya?).

Cell-mediated immunity. Immunity that uses or requires cells. There are many different types of immune cells. Some cells directly kill pathogens (natural killer cells). Some cells produce antibodies (called B-cells). Some cells help other cells do their jobs (helper T-cells). Different infections may require different types of an immune response. The most protective and longest lasting types of immunity usually need both antibodies and cells.

Respiratory mucosa. The innermost lining of the mouth, nose, and the airway that extends all the way down to the lowest depths of the lungs. This lining is where COVID-19 infects the human body.

Sterilizing immunity. Immunity that prevents infection. 

Viremia. Viral replication in the blood. Although COVID-19 does not primarily infect the blood, there is some evidence that the virus can infiltrate the blood, which is likely how the virus spreads from the respiratory tract to other organs. The presence and the amount of viremia is associated with severe disease (not surprising).