Federal regulators authorized next-generation COVID-19 boosters from Moderna and Pfizer, despite scant data on how effective and durable booster-induced immunity will be.
The new bivalent vaccines, which target both the original COVID-19 strain and newer Omicron variants, will now be the only booster option for people ages 12 and older.
The Centers for Disease Control and Prevention (CDC) recommends everyone in this group gets the updated shot at least two months after their most recent booster or their last primary series dose. Those who had a recent infection may consider delaying their booster dose by three months from symptom onset or a positive test.
There is no data on how well the new boosters work in humans. Instead, regulators looked to animal studies and clinical trial data on the companies’ BA.1-bivalent boosters. These data suggested the reformulated boosters may be as effective as the old vaccines and are likely better at neutralizing Omicron.
By authorizing a vaccine that targets Omicron BA.4 and BA.5, U.S. health authorities are betting that the booster can tackle the variants that present the timeliest threat. Making the bivalent shots available in September rather than November could prevent 137,000 more hospitalizations and 9,700 more deaths, assuming the same number of adults get boosted as receive the flu shot.
“We fully expect that the updated bivalent vaccines containing BA.4 and BA.5 sequences will offer better protection against currently circulating strains than the original vaccines, although it is difficult to predict at this point how much better that protection will be,” Anthony Fauci, MD, chief medical advisor to the White House, said in a press briefing.
In Europe and Canada, health officials opted for a bivalent vaccine that targets BA.1—an older version of the vaccine for which there is more human data.
The best vaccine data comes from clinical trials in people. But these trials take longer, as researchers need to recruit people to participate and check on how they respond to the vaccine over time.
Earlier this year, Moderna and Pfizer each developed and tested a bivalent vaccine geared toward BA.1, the original Omicron strain.
Pfizer tested its BA.1 bivalent booster in people 55 years and older around six months after their last shot. Participants who had no evidence of prior infection saw a 1.56-fold increase in antibodies after a month.
In participants ages 18 and older in Moderna’s trial, antibody levels induced by the bivalent vaccine improved 1.75-fold over the original vaccine.
In both cases, people who got the BA.1 bivalent shot had higher levels of antibodies against all COVID-19 variants, including Beta and Alpha, compared to the older vaccine.
Although Moderna and Pfizer have not completed human trials on the updated BA.4/BA.5 bivalent boosters, they tested the vaccines in mice.
Mice are particularly useful because they have a special protein called angiotensin-converting enzyme 2 (ACE2). In humans, this protein is the port that allows the COVID-19 virus to enter cells and cause an infection.
The Moderna bivalent vaccine boosted neutralizing antibodies in mice at least 4.2-fold. Animals inoculated with the Pfizer bivalent booster saw a 2.6-fold increase in antibodies.
That’s an improvement from the original boosters, but far less impressive than the 25-fold increase in antibodies afforded by the first round of boosters.
However, while higher antibody levels generally indicate that a vaccine performs well, scientists still aren’t sure exactly how high these levels must be to provide good protection. Besides, other immune cells, including memory B- and T-cells, play key roles in ensuring long-term protection. It's more challenging to measure the role boosters play in spurring these long-lasting immune cells.
Throughout the pandemic, scientists have used mouse models to get a sense of how well different vaccines and treatments will perform in humans. The results usually align pretty well, said Kathryn M. Edwards, MD, FIDSA, a professor of pediatrics at the Vanderbilt University School of Medicine and fellow at the Infectious Diseases Society of America.
“Over and over again, we have seen with the SARS-CoV-2 vaccines that mouse responses mirror human responses, so I’m really not concerned at all about that,” Edwards said in a media briefing. “I’m much more happy to get a vaccine to a strain that’s circulating than to a strain that was circulating six months ago.”
Moderna's and Pfizer's messenger RNA (mRNA) vaccine technologies allow scientists to easily tweak the formula to target new variants without having to create a new vaccine from scratch. Edwards and other experts said that thanks to this technology, COVID-19 vaccines may be updated periodically to match current variants, as is done with the influenza vaccine each year.
Both companies are running clinical studies to test their BA.4/BA.5 bivalent booster and say they will report findings by the end of the year. Pfizer is also testing its BA.1-specific booster in children 6 months to 5 years old, and Moderna plans to submit data on its BA.1 bivalent booster in people 6 to 17 years old in mid-September.
It will take months of studying infections and antibody levels among people who were vaccinated with the new bivalent boosters to understand how long-term the booster-induced immunity is.
“I remain confident that the bivalent vaccine we have right now will provide a high degree of protection with, you know, some durability. But in the long run, we’re going to need a different game in terms of much more durable vaccines,” White House COVID-19 Response Coordinator Ashish K. Jha, MD, MPH, said in a briefing.
Jha said federal officials aim to give out COVID-19 boosters annually, as is done with flu shots. This approach may be adequate so long as there are no major “variant curveballs.”
There are efforts underway to create a universal vaccine for COVID-19 that would protect against all viral variants with a single formula, according to Edwards. In the meantime, she is hopeful that the boosters could be quickly modified should a new, immune-evasive variant emerges.
You can get the updated COVID-19 booster shot two months after receiving your last booster shot or three months after recovering from an infection. You can schedule a vaccine appointment at vaccines.gov or talk to a health provider about when to get the shot.
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