COVID Transmissions for 6-30-2021
How long are you protected? mRNA vaccines likely to have long duration of immunity.
Greetings from an undisclosed location in my apartment. Welcome to COVID Transmissions.
It has been 590 days since the first documented human case of COVID-19. In 590, the Franks and Burgundians invaded Italy but were forced to retreat after a plague outbreak. The running theme of how disease has shaped human history continues—imagine, if not for plague, Italy could be part of France.
Today we’ll talk about a new study showing that immunity to COVID-19 from mRNA vaccines might last for years.
Then, some reader comments.
Bolded terms are linked to the running newsletter glossary.
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Now, let’s talk COVID.
No booster? New study suggests that SARS-CoV-2 immune responses to mRNA vaccines are likely to be long-lasting
A new study in Nature has provided compelling evidence that immune responses generated by mRNA vaccines are likely to be long lasting: https://www.nature.com/articles/s41586-021-03738-2
First, the upshot. If these results are accurate and a good model for reality, then it suggests that immunity induced by these vaccines could last for years.
This study focused on B cells, which is the class of cells that produces antibodies. While the initial response to vaccination produces large amounts of antibodies, the researchers found that blood levels of antibodies drop rapidly after infection. However, that is not the be-all and end-all of antibody-mediated immunity. You see, antibodies are generally produced at great speed and volume when an infection is encountered for a second time, provided there is a memory B cell population to divide, expand, and make those antibodies. What is generally really important, then, is the establishment of well-trained memory populations.
B cells tend to mature after immunization (either by natural infection or by vaccination) in the lymphatic system. The researchers here went looking for B cells that reacted to SARS-CoV-2 S protein, the vaccination target, and found that these B cells persisted in the lymphatic systems of the study patients for at least 12 weeks. That’s a really long time; normally you would expect to see B cell maturation continuing in the lymphatic system for a few weeks after an infection. The persistence of this response suggests that the immune memory generated by mRNA vaccines here will also last for quite some time. This builds on prior work from this group and others that has shown that memory B cells responding to natural COVID-19 infection can also persist in the lymphatic system for periods of months to a year—at least! So taken together this leaves us with an overall impression that the response will be long-lived.
Furthermore, they extracted some of these B cells and characterized them. They found that these cells displayed gene expression patterns when stimulated that characterized them as memory cells. This is an important step, because memory cells can be very long-lived, and it helps to establish that what the researchers detected represents the formation of a genuine memory response, and not just left over defective antibody-producing cells from the initial immune response.
Apoorva Mandavilli of the New York Times wrote up a story on this here: https://www.nytimes.com/live/2021/06/28/world/covid-vaccine-coronavirus-mask#a-study-finds-that-the-pfizer-and-moderna-vaccines-could-offer-protection-for-years
This is rather good news, and validates my skepticism when the CEO of Pfizer claimed that we could all expect to need a booster vaccination every year. I don’t anticipate that based on these results. Boosters may be needed eventually, but I don’t think that they will be needed on an annual schedule.
What am I doing to cope with the pandemic? This:
Heat Wave
This week, I’ve been trying to stay inside and isolate myself from others. Not because of COVID-19 though. Because it’s too hot! And the New York City temperatures haven’t even been that bad. If you’re out in the Pacific Northwest…hang in there. I can’t believe what’s happening in your area.
Carl Fink had a comment about the expected completion date of the Johnson and Johnson 2-dose ENSEMBLE 2 trial:
According to the Clinical Trials Registry (https://clinicaltrials.gov/ct2/history/NCT04614948?V_14=View#StudyPageTop) ENSEMBLE 2 is expecting completion in May, 2022. The study design is also two doses of placebo vs. two doses of Ad26.COV2.S (not 1 vs. 2 doses as I personally would have expected). The two-placebo subjects would receive a single dose of the vaccine at unblinding, but that page doesn't state when unblinding would occur.
I am guessing you were expecting preliminary data by now?
These registry sites can be pretty misleading if you’re not familiar with how they work (and why should anyone be, if they don’t explicitly work in this field?). Here’s my explanation:
This is the thing about ClinicalTrials.gov; it's not very approachable. The study completion date isn't always the date that the "final analysis" is actually released. Often, particularly in studies with long safety follow-up or that use a surrogate endpoint to predict clinical outcomes, there is a projected study duration that represents the expected completion date of the trial, but doesn't represent the data that people are most interested in.
In this case, the safety evaluations for most of the COVID-19 vaccines are expected to continue for about two years past study onset, which is probably was generated this date.
The efficacy evaluation, meanwhile, is event-driven, and so won't have a fixed final analysis date. Instead, it will depend on when enough events have accrued in the trial (events here being COVID-19 cases). Since there was no shortage of COVID-19 events over the winter when the trial was expected to read out, I'm really confused as to why it hasn't read out yet.
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Always,
JS