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• Posted January 11, 2023

Bivalent COVID Boosters Offer No Extra Protection, Studies Suggest

The updated COVID-19 vaccine boosters intended to defend people against emerging Omicron variants don't appear to provide any better protection than the original shot does, two new studies find.

The new mRNA bivalent boosters produced by Moderna and Pfizer only attack the COVID-19 virus about as well as the companies' first-wave vaccines, according to a blood testing study led by renowned virologist Dr. David Ho, a professor of microbiology and immunology at Columbia University, in New York City.

The bivalent shots also failed to promote higher antibody levels or a better immune response than the original COVID-19 vaccines, according to another study led by Dr. Dan Barouch, director of the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center, in Boston. Both studies were published online Jan. 11 in the New England Journal of Medicine.

Together, the two studies "suggest that with this rapidly evolving virus, vaccines developed for different strains are not going to add a huge difference in terms of protection,"said Dr. Greg Poland, director of the Mayo Clinic's Vaccine Research Group.

It appears that human immune systems "imprint"after exposure to the first mRNA COVID vaccines, experts say. They are primed to respond to aspects of the original COVID-19 strain that are shared by all the variants, rather than the novel mutations sported by newer variants.

The upshot -- people will receive a temporary increase in COVID-19 antibodies from a bivalent booster, but the antibodies aren't necessarily that much better at targeting newer variants.

"You really don't develop any higher levels of antibody with this fourth bivalent booster than you do with the third, because your body thinks, 'Oh, it's just the same thing,'"Poland explained.

These results add to controversy already swelling around the federal approval process for the bivalent boosters.

The initial notion behind the bivalent boosters was to add a component to the original mRNA vaccines that also would create an immune response against the Omicron BA.4 and BA.5 variants -- similar to how flu shots protect against as many as four different strains of influenza.

More than 48 million Americans aged 5 and older have gotten a bivalent booster, according to the U.S. Centers for Disease Control and Prevention.

U.S. taxpayers paid $3.2 billion for 105 million doses of the Pfizer bivalent booster, and another $1.7 billion for 66 million doses of the Moderna bivalent, according to the Kaiser Family Foundation.

However, advisors to the U.S. Centers for Disease Control and Prevention and the U.S. Food and Drug Administration now say they were not provided real-world data about how well the bivalent booster kept people from actually catching COVID-19 prior to the boosters' approval.

That data showed that 1.9% of people who got the original booster became infected, versus 3.2% of people who got the updated bivalent vaccine, according to CNN.

"I was angry to find out that there was data that was relevant to our decision that we didn't get to see,"Dr. Paul Offit, a member of the FDA's Vaccines and Related Biological Products Advisory Committee, told CNN. "Decisions that are made for the public have to be made based on all available information -- not just some information, but all information."

A rethink on boosters?

The two studies show there needs to be a reassessment of how future COVID vaccines are developed, experts say.

COVID-19 simply evolves too quickly to be able to create boosters aimed at preventing the newest variants, Poland said.

"You cannot make mRNA vaccine boosters and get them approved fast enough to keep up with the rapid mutation in these variants,"Poland said, noting that the XBB variants have now superseded the BA variants that were targeted by the bivalent vaccine.

In fact, further COVID boosters might not be needed for average people unless the coronavirus mutates in some way that makes it more deadly, said Offit, who is director of the Vaccine Education Center at the Children's Hospital of Philadelphia.

That's because the memory cells of the human immune system -- the T-cells -- appear to learn a lasting and valuable lesson from the original vaccines and boosters, Offit explained.

Thanks to vaccination, the T-cells have learned to recognize COVID's basic form and then produce enough antibodies to prevent severe disease, regardless of the newer mutations.

"Assuming you're not in a high-risk group, while it is true that immunity wanes for protection against mild disease, it doesn't wane for protection against severe disease,"said Offit, who also wrote a commentary in the NEJM on the two new studies.

"Until the CDC can show data that a healthy person, despite three doses, is getting hospitalized, then I think we know that we're still having fairly long-lived protection against severe disease,"Offit added.

Offit said he's gotten three doses of vaccine, the last in November 2021.

"Seven months later, I had a mild two-day illness with probably BA.2, one of the Omicron subvariants,"Offit said. "But I was protected against severe disease because I've been vaccinated."

"I suspect I will be protected against severe disease for years,"Offit continued.

Poland agreed that initial vaccination will make the average person more likely to get an asymptomatic, mild or, at worst, moderate case of COVID-19.

However, Poland believes that boosters are still needed, if only to help prevent complications like long COVID.

"What amount of research we do have so far, and I would call it incomplete, suggests that the risk of so-called long COVID is reduced by 20%, 25%, something like that"through vaccination, Poland said.

In addition, real-world studies are showing a benefit from the bivalent booster in older people, said Dr. William Schaffner, medical director of the National Foundation for Infectious Diseases.

Schaffner pointed to a new Israeli study that found an 81% reduction in hospitalizations among people 65 and older who had received the bivalent booster, compared to people who'd gotten at least two vaccinations but not the new vaccine.

"I keep pushing people at high risk to be at the forefront of folks getting this booster vaccine,"Schaffner said. "And it's not that I'm going to tell the other folks they don't have to. I'm just going to keep emphasizing that this vaccine is most important for the people who are at high risk."

In the meantime, vaccine development efforts need to shift toward preventing infection with COVID-19 in the first place, Poland argues.

For example, a nasal vaccine could be a breakthrough.

"You develop an antibody in the nose and the mouth so that the portal of entry, how we actually get infected with the virus by breathing it in, we've neutralized the virus right at that portal of entry,"Poland said.

Better vaccines are crucial because COVID-19 has mutated in ways that have made monoclonal antibody treatment ineffective, Poland explained.

The only options for treating COVID-19 now are antiviral drugs like Paxlovid, remdesivir and molnupiravir, Poland said.

"Many of us are just holding our breath,"Poland said. "Are we going to see new variants develop that are resistant to these antivirals? Once that happens, we are in a world of hurt."

Was data withheld?

In June 2022, Pfizer and Moderna researchers presented data on the bivalent vaccines to the FDA's advisory committee, Offit wrote in the NEJM commentary.

"The results were underwhelming,"Offit wrote, noting that the bivalent boosters prompted antibody levels against the BA.1 variant that were only 50% to 75% higher than the response from the original vaccines.

Despite this, the FDA and the CDC pursued a series of "rapid-fire policy decisions"in September and October that led to the approval and recommendation of the bivalent boosters.

Vaccine advisors now say that they were not given all the data on hand when asked to evaluate the bivalent boosters in June and September.

Data showing that the original vaccine prevented more infections than the bivalent booster was available, but apparently not provided to advisors during their deliberations, CNN reported.

Six FDA and CDC advisers interviewed by CNN said the data wouldn't have changed how they voted, due to limitations of the data.

However, they insist it still should have been presented to them.

"There should always be full transparency,"Dr. Arnold Monto, a professor of epidemiology at the University of Michigan School of Public Health and acting chair of the FDA advisers' group, told CNN. "These data should not be dismissed. They are early, but they indicate that we need to look at them and see what their value is."

The CDC in October recommended the bivalent booster for everyone aged 5 and older. Less than two weeks later, Ho and his team released their data showing no significant difference in effectiveness between the bivalent booster and the original vaccine, Offit wrote in his editorial.

A day later, Barouch and his team released their similar findings.

Both preprint papers have now been published in the NEJM.

Offit said he's concerned that a continued push for boosters that don't have added effectiveness could create a "boy that cried wolf"scenario with the American public.

"We keep saying, let's get a bivalent vaccine containing this strain and let's get it containing that strain,"Offit said. "Then when a 'wolf' really does come along, a strain that is resistant to T-cell recognition, you are going to have habituated the population to the notion that it's not important."

More information

The U.S. Food and Drug Administration has more about the bivalent COVID boosters.

SOURCES: Greg Poland, MD, director, Mayo Clinic's Vaccine Research Group, Rochester, Minn.; Paul Offit, MD, director, Vaccine Education Center, Children's Hospital of Philadelphia; William Schaffner, MD, medical director, National Foundation for Infectious Diseases; New England Journal of Medicine, Jan. 11, 2023, online; CNN