Why do we need two doses of the COVID-19 vaccine? Can we use one dose and vaccinate more people?


A: A two dose schedule was proven to work and authorized for both the Pfizer and Moderna COVID-19 vaccines.

One dose provides sub-optimal immunity and has not been studied in clinical trials designed to test their efficacy. Giving one dose of these vaccines to the most vulnerable populations would leave them without full immune protection.

Pfizer and Moderna vaccines were both tested and authorized in a two dose schedule. Because they were approved as a two dose schedule, both doses need to be given either 21 days apart for Pfizer vaccine or 28 days apart for the Moderna vaccine. While there is an estimated 52% vaccine efficacy for the Pfizer vaccine and 80% efficacy for the Moderna vaccine after the first dose, we do not know how long that protection lasts. Two doses provides substantially greater protection (95% vaccine efficacy) and we know that this immune response lasts at least several months and perhaps even years (to be determined).

Giving multiple doses of a vaccine is commonly used with multiple vaccines that we have received. Most childhood vaccinations are in multiple doses including MMR, Hepatitis B, rotavirus, chickenpox, haemophilus influenzae B, TDAP, etc The reason why vaccines are given in multiple doses is due to an immunology principle called “Prime-Boost”.

The first dose of the COVID-19 vaccine works to “prime” the immune system to recognize the spike protein of SARS-CoV2, a small part of the virus that it uses to get into the cells.. Each immune cell uses a receptor on it that is like a snowflake- it is unique. The immune cells that recognize the spike protein- something the body has never seen before – are extremely rare. The first vaccine dose gets the immune cells that recognize the spike protein to expand and to start producing antibodies against the spike protein.

The second dose of the COVID-19 vaccine is a “boost” to the cells which initially responded. Now when the body sees the spike protein there is already a group of cells waiting to respond against it. The “boost” dose substantially increases the number of cells that recognize the viral protein, the spike protein, which leads to higher levels of circulating antibodies. The boost dose also promotes the immune cells to become MEMORY cells. The memory cells will last in your body for much longer.

Now that your body is tricked into thinking it saw the viral spike protein twice, it has an army of immune cells which includes memory T cells, B cells and antibodies. Your immune system will remember the spike protein should you become exposed to SARS-CoV2. Some of the antibodies are neutralizing and will prevent the spike protein of the virus from gaining entry to your cells. The immune system will prevent the SARS-CoV2 from causing disease. The ability to prevent disease over time was only tested with two doses of the Pfizer and Moderna vaccines.

In addition to measuring the number of people that had viral symptoms of COVID-19, scientists from both companies measured the immune responses to the vaccine over time. It is clear from measuring the immune system responses that “prime-boost” is working. After one dose of the vaccine there were antibodies against the spike protein produced. After the second dose of the vaccine, these levels are much higher and importantly there are many more of the neutralizing antibodies. Scientists can take the antibodies and determine how many can neutralize a virus in a culture dish. The difference between the numbers of neutralizing antibodies between one dose and two doses is very striking to me even as an immunologist (who has worked on vaccines and in clinical trials). The original papers are linked below. Both Pfizer and Moderna vaccines had similar data.

There is an exception, the Janssen vaccine uses a different technology and is being tested as a single dose. Because it is being tested in clinical trials as a single dose of vaccine, if approved it can be administered as a one dose vaccine. The other vaccines in development for Operation Ward speed within the US are testing two dose injections (including the GSK, NovaVax and Astrazeneca vaccines) .

Giving one dose of vaccine in order to preserve the number of vaccine doses available is attractive however this has not been tested and does not provide the full benefit of the immune responses to those that are given the vaccine. Although there are immune responses to one dose, the number of neutralizing antibodies are higher with the second dose and it is likely that the second dose will result in longer immune protection against COVID-19. Especially because we are vaccinating our most vulnerable populations first, we should provide these populations with the vaccine regime that was proven in clinical trials to provide substantial protection. Using only one dose would be experimenting with these populations by using an unauthorized regimen and not providing the full benefit of protection.

Pfizer vaccine antibody responses (Figure 4, most relevant is 30 ug dose BNT162b2)

Moderna vaccine antibody responses (Figure 2, most relevant is 100ug dose)

Also here

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