As the U.S. is experiencing vaccinations due to the shortage of workers and distribution problems, federal health officials say it is OK to push back the second dose of two-part vaccine by as much as six weeks.
As a doctor on infectious diseases, I have asked many questions from my patients as well as my friends and family about whether the COVID-19 vaccine will still work if people are too late to receive their second dose.
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 makes the immune system primary and introduces the body to the germ of interest. This enables the immune system to prepare its defenses. The second dose, or enhancer, provides the chance for the immune system to increase the quality and quantity of the antibodies used to fight the virus.
In the case of Pfizer and Modern COVID-19 vaccines, the second dose increases the protection provided by the vaccine from 60% to about 95%.
The reason why the CDC decided to receive the second dose within 42 days is OK
In the clinical trial, the second dose of the Pfizer vaccine was administered on day 19 and as late as day 42 to 93% of the subjects. Since protection was about 95% for everyone vaccinated within this ‘window’, there is little reason not to make the timing of the second dose 2 so flexible.
As more vaccines become available, the second dose for the Pfizer and Moderna vaccines should be about four weeks. But the good news is that although stocks are 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 the mRNA vaccines cause their protection against COVID-19 is fundamentally different from that with other vaccines.
Pfizer and Moderna vaccines use messenger RNA that encodes the spike glycoprotein. After injection of the vaccine, the mRNA enters immune cells called dendritic cells. The dendritic cells use the instructions written in the mRNA to synthesize the characteristic peak glycoprotein, which characterizes the SARS-CoV-2 virus that causes COVID-19. These immune cells then display the peak glucoprotein to B cells, which then form anti-spiked bodies.
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The mRNA vaccines are uniquely capable of eliciting a special type of immune cell – called a T-follicular helper cell – to produce B-cells antibodies. The T cells do this by direct contact with the B cells and by sending chemical signals that tell the B cells to produce antibodies. This aid in the production of antibodies makes these vaccines so effective.
But not all B cells are the same. There are two types that make anti-hereditary antibodies: long-lived plasma cells and memory B cells. The long-lived plasma cells live, as their name suggests, years after vaccination in the bone marrow, which constantly eliminates the antibody – in this case anti-venous body. These long-lived B cells do not need to be amplified.
The memory B cells, on the other hand, live in a similar state to hibernation. They do not produce antibodies before they are stimulated by the vaccine, or are exposed to infection with the coronavirus that causes COVID-19. This is why we need the second dose. Together, these two types of B cells provide a constant level of protection.
What happens if you do not get the second dose of Pfizer or Moderna on time?
With the current shortage of vaccines and problems in setting up the infrastructure to vaccinate millions of people, many doctors are worried that the second dose of vaccine will not be delivered in the prescribed window of three to four weeks.
The booster shot is needed for the T cells to stimulate the memory B cells to produce large amounts of antibodies. If the enhancer is not given within the appropriate window, lower amounts of antibodies are produced which may not be as potent against the virus.
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