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A mostly empty vaccine center at the Berks Cares Vaccine Center in Muhlenberg Township, PA, on July 1, 2021. Ben Hasty/MediaNews Group/Reading Eagle via Getty Images
  • Research has found a significant fall in levels of antibodies against SARS-CoV-2, the virus that causes COVID-19, 6 months after the second dose of the Pfizer-BioNTech vaccine.
  • Clinical evidence also suggests that the risk of getting a “breakthrough” infection gradually increases in the months after vaccination.
  • Despite declines in antibody levels, other branches of the adaptive immune system appear to provide strong protection against severe infection and death.
  • However, booster shots could protect the most vulnerable individuals, reduce transmission, and help suppress the emergence of new strains.

In the United States, the Food and Drug Administration (FDA) has approved third doses, or “boosters,” of the Pfizer-BioNTech COVID-19 vaccine for people over the age of 65 years.

It also approved boosters for people with health conditions that put them at risk of severe COVID-19 and for people whose jobs expose them to a high risk of infection, including healthcare workers and teachers.

The agency had already given the green light to boosters for individuals with severely weakened immune systems, such as organ transplant patients.

But is there any evidence to justify a more widespread rollout of booster shots in the general population?

A recent study found that serum levels of antibodies against the spike protein of the virus, which it uses to gain entry to cells, start to wane around 12 weeks after the second dose of the Pfizer vaccine.

The researchers discovered that by 6 months after the second dose, median levels of these antibodies had fallen to around 7% of their peak level, with a range of 2–25%. The researchers say that this decline is expected.

Other work has shown that after having an mRNA-based vaccine against SARS-CoV-2, antibodies may not be circulating, but they are at peak activity within the lymph nodes by 12 weeks.

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At first glance, this appears to represent a worrying loss of immunity, but antibodies are only one branch of the body’s adaptive immune system.

The adaptive immune system also includes cells that remember past infections or vaccinations and swing into action if they encounter the same infectious agent again.

A recent preprint of a study reports that the number of immune cells known as memory B cells that recognize the virus actually increases 3–6 months after the second dose of the Pfizer or Moderna vaccine.

Remarkably, even though these vaccines use genetic material from the original variant of the virus, the B cells also recognized the Alpha, Beta, and Delta variants.

This is because the precursors of these B cells evolve over time in the body through a process of random mutation, which allows the mature cells to detect new variants of the virus as they arise.

The research also found two other types of immune cell primed to detect the virus in most individuals 6 months after their second dose of vaccine.

Known as helper T cells (CD4+ cells) and killer T cells (CD8+ cells), these help ramp up the immune response and destroy infected cells, respectively.

These findings help explain why vaccines continue to provide good protection against infection and severe illness in most people.

A recently published follow-up of a clinical trial found that while there was a gradual decline in efficacy, the Pfizer vaccine remained 91.3% effective over 6 months after the second dose. The peak of protection was 96.2%, which fell to 83.7% at 4 months, a decline of 6% per month.

In South Africa, where the Beta variant of the virus is prevalent, efficacy was even higher. The Pfizer vaccine’s ability to prevent severe disease was 96.7% on average.

However, several observational studies have suggested that older people have a substantially increased risk of infection several months after vaccination.

For example, a preprint of a study in Israel notes that older people who received their second dose at the start of 2021 had almost twice the risk of severe illness during an outbreak in July 2021, compared with individuals vaccinated more recently.

Data from the United Kingdom suggests a small but significant decline in protection against hospitalization and death 20 weeks after the second dose of the Pfizer or Oxford-AstraZeneca vaccine in the population as a whole.

But the decline was steeper among older adults and those with health conditions that put them at greater risk of severe COVID-19.

Crucially, however, another study in Israel found that older adults who received a booster shot were less likely to get a SARS-CoV-2 infection or develop severe illness than those who did not get the shot.

In addition to reducing the risks for older adults, a campaign of booster vaccinations for vulnerable individuals may help slow the transmission of the virus through populations.

A 2021 modeling study suggests that minimizing transmission reduces the likelihood that more dangerous, vaccine-resistant strains of the virus will emerge.

Other countries are going further than the U.S. in their booster vaccination campaigns. In the U.K., for instance, everyone over the age of 50 years will be offered a booster.

However, some critics believe it is irresponsible to give third doses of vaccine to people who are not especially vulnerable while much of the world remains unvaccinated. As the World Health Organization (WHO) explained in a press briefing:

“Third doses should be prioritized for the vulnerable: those most at-risk populations when there is evidence of waning immunity against severe disease and death. They are not for the fit and healthy. […] [W]hen global supplies are so limited, when the world is in a place where billions of people have not yet received any doses, we must focus on administering first and second doses.”

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