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As the United States faces vaccination delays due to worker shortages and distribution issues, federal health officials now say it’s okay to postpone the second dose of the two-part vaccine until ‘at six weeks.
As an infectious disease physician, I have answered many questions from my patients, friends and family about whether the COVID-19 vaccine will still work if people get their second dose late. .
Why you need two doses 3-4 weeks apart
Two doses, separated by three to four weeks, is the proven approach to generate an effective immune response through vaccination, not only for COVID, but also for hepatitis A and B and other diseases.
The first dose triggers the immune system and introduces the body to the germ of interest. This allows the immune system to prepare for its defense. The second dose, or booster, allows the immune system to increase the quality and quantity of antibodies used to fight the virus.
In the case of the Pfizer and Moderna COVID-19 vaccines, the second dose increases the protection offered by the vaccine from 60% to about 95%.
Why the CDC decided to receive the second dose within 42 days.
In the clinical trial, the second dose of Pfizer vaccine was given on day 19 and as late as day 42 in 93% of subjects. Since protection was around 95% for all people vaccinated within this time “window”, there is little reason not to allow flexibility in the timing of the second dose 2.
As more vaccines become available, the timing of the second dose is expected to be close to four weeks for Pfizer and Moderna vaccines. But the good news is that even though supplies remain limited, science suggests that there is nothing wrong with getting a second dose as late as 42 days after the first.
What the immune system does between the first and second dose
The biology by which mRNA vaccines induce their protection against COVID-19 is fundamentally different from that of other vaccines.
The Pfizer and Moderna vaccines use messenger RNA which encodes the spike glycoprotein. When the vaccine is injected, mRNA enters immune cells called dendritic cells. Dendritic cells use the instructions written in mRNA to synthesize the characteristic spike glycoprotein, which characterizes the SARS-CoV-2 virus that causes COVID-19. These immune cells then show the spike glycoprotein to B cells, which then make anti-spike antibodies.
MRNA vaccines are only able to induce a special type of immune cell – called a follicular T helper cell – to help B cells make antibodies. T cells do this by direct contact with B cells and by sending chemical signals that tell B cells to make antibodies. It is this help in the production of antibodies that makes these vaccines so effective.
But not all B cells are the same. There are two types of anti-spike antibodies: long-lived plasma cells and memory B cells. Long-lived plasma cells, as the name suggests, live in the bone marrow for years after vaccination, continuously producing antibodies – in this case anti-spike antibodies. These long-lived B cells do not need to be stimulated.
Memory B cells, on the other hand, live in a state close to hibernation. They do not produce antibodies until they are stimulated by a vaccine booster, or are not exposed to infection with the coronavirus that causes COVID-19. This is the reason why we need this second dose. Together, these two types of B cells provide a consistent level of protection.
What happens if you do not receive the second dose of Pfizer or Moderna on time?
With current vaccine shortages and problems setting up the infrastructure to immunize millions of people, many doctors are concerned that the second dose of vaccine may not be given within the prescribed window of three to four weeks.
This booster injection is necessary for the T lymphocytes to stimulate the memory B lymphocytes to produce massive amounts of antibodies. If the booster is not given within the appropriate window, smaller amounts of antibodies will be produced which may not provide as strong protection against the virus.
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This article is republished from The Conversation, a nonprofit news site dedicated to sharing ideas from academic experts. It was written by: William Petri, University of Virginia.
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William Petri receives research funding from NIH, the Bill & Melinda Gates Foundation, and Regeneron, Inc.
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