The fact that we have an updated bivalent booster dose that targets the predominant variants circulating today is a wonder of science, but how do we know it’s safe and effective?
In late June, the U.S. Food and Drug Administration (FDA) weighed administering the original COVID-19 vaccine as the next round of booster doses against asking manufacturers to develop an updated version. The agency evaluated several options.
Moderna and Pfizer had already produced updated bivalent vaccines that targeted the Omicron BA.1 subvariant. These vaccines went through clinical trials, produced more antibodies against Omicron subvariants than the original vaccine, and were ultimately approved and rolled out in the United Kingdom over the summer.
The FDA, however, recommended vaccine manufacturers design updated bivalent boosters to specifically fight the BA.4 and BA.5 Omicron subvariants, in addition to previous subvariants. Let’s examine some of the reasons for that decision.
What is a bivalent vaccine?
A bivalent vaccine targets two things. In this case, it targets two strains of the virus that causes COVID-19. The recently released updated bivalent booster vaccine from Moderna and Pfizer contain messenger RNA (mRNA) that tells our cells to build:
- The “spike” protein from the first strain of COVID-19 that emerged more than two years ago, which is the target of the original vaccine.
- The “spike” proteins from the Omicron BA.4 and BA.5 subvariants (identical to each other) that are responsible for about 98% of COVID-19 cases in the United States today.
This means the updated booster vaccine better protects us against the subvariants circulating today than the original vaccine does.
“Adding a component to the boosters that specifically targets the subvariants currently circulating will help restore protection against COVID-19 infections, including hospitalizations, that has decreased over time,” said Dean Sidelinger, M.D. MSEd, health officer and state epidemiologist at Oregon Health Authority. “This is especially important as we head into the fall, when cases across Oregon and the United States are expected to increase.”
Additionally, the bivalent booster still has instructions to build COVID-19’s original “spike” protein for a few important reasons:
- The original vaccine has been highly effective at preventing COVID-19-related hospitalizations and death over the past two years (including all variants and subvariants).
- Bivalent vaccines cast a wider net that may better protect us against future variants.
- A bivalent vaccine may provide higher levels of immunity for a longer period of time.
Why do we need an updated vaccine?
The virus that causes COVID-19 has evolved significantly since it first appeared nearly three years ago. The Omicron spike protein alone has mutated more than 30 times since the original vaccine was designed. These mutations allow the virus to better evade immunity, allowing it to infect people more easily. The updated booster dose, on the other hand, builds more antibodies for the virus strains circulating today.
Are booster doses effective?
Immunity from COVID-19 vaccines (and infection) declines over time. This is why we need a booster dose. While we’ve seen an increase in breakthrough infections since Omicron arrived in Dec. 2021, booster doses have remained incredibly effective at protecting us from COVID-19-related hospitalization and death:
- During the peak of the Omicron surge from January through March 2022, people age 5 and older who were unvaccinated were 20x more likely to die from COVID-19 compared to somebody who had received at least one booster dose.
- In June 2022, unvaccinated people age 5 and older were 8x more likely to die from COVID-19 compared to somebody who had received at least one booster dose.
- In June 2022, unvaccinated people age 50 and older were 14x more likely to die from COVID-19 compared to those who had received at least two booster doses. Also in June, people age 50 and older who had received one booster dose were 3x more likely to die from COVID-19 than those who had received at least two booster doses.
Is it safe?
We know mRNA COVID-19 vaccines are safe. More than 590 million doses have been administered in the United States alone over the past two years, and serious health problems after vaccination are rare. The overall composition of the updated booster dose is the same as the original booster dose, but the spike protein it tells our cells build is slightly different.
Both Moderna and Pfizer held human clinical trials of bivalent vaccines that target the original strain and the BA.1 Omicron subvariant that showed the vaccines to be safe. It is true that the BA.4 and BA.5 version of the bivalent vaccine has only been tested in mice, but there is no reason to anticipate a difference in the safety of this updated vaccine based on limited mutations in the spike protein it creates. COVID-19 vaccines have a “high degree of safety” (slide 67). The updated BA.4 and BA.5 bivalent vaccine, which has been given emergency use authorization by the FDA and the Centers for Disease Control and Prevention (CDC), is currently undergoing human trials now in order to receive full approval from federal health officials.
The flu shot does not have human trials every year. Flu shots are safe.
“This process is not new and is in fact very similar to the annually updated flu shots we receive each year,” Sidelinger said. “Because the circulating strains of flu change, components of the vaccine change to better protect us. These changes don’t impact the well-established safety of the vaccines.”
Updates to authorized vaccines do not require human trials for safety. Their safety is already known. The challenge is matching a vaccine to the most prevalent known strains of a virus.
Additionally, producing the flu vaccine require growing a virus in chicken eggs, and it takes at least six months to produce enough vaccine for the nation’s population. Because the flu virus mutates from year to year, producing multiple strains globally, scientists must decide which strains to target for vaccines months before flu season begins every fall. This is one of the reasons flu vaccines, although still critical to preventing severe illness, are often less than 50% effective in preventing infection.
One of the incredible aspects of “plug and play” mRNA technology is how fast an mRNA vaccine can be developed once the genetic code of the virus is known.
In late June, the FDA examined the human trials for an updated bivalent booster based on the Omicron BA.1 subvariant. Scientists on the FDA’s advisory panel concluded the bivalent vaccine improved the antibody response to the Omicron variant. However, they predicted that Omicron’s BA.1 subvariant would no longer be predominant by the time the updated vaccine would be available in September. So instead, the FDA panel recommended Moderna and Pfizer manufacture a bivalent vaccine that targets both the original strain and BA.4/BA.5. The result: we have an updated booster dose specifically designed to fight the variants that account for 98% of all COVID-19 cases in the U.S.
The FDA correctly predicted BA.4 and BA.5 would become the predominant subvariants. This ability to rapidly create an updated vaccine targeting new or emerging variants or subvariants showcases the speed of mRNA technology.
If you are interested in knowing more, review the slides from the CDC’s Advisory Committee on Immunization Practices’ Sept. 1-2 presentations on updated bivalent booster doses.