Aug. 31, 2022 – COVID-19 booster vaccines targeting the Omicron BA.4 and BA.5 subvariants that currently dominate the U.S. could be available in the next few days, but their arrival has brought some controversy .
U.S. Food and Drug Administration Get emergency approval To today Pfizer and Moderna’s mRNA enhancers. Next up are meetings of the CDC’s Advisory Committee on Immunization Practices on Thursday and Friday, which could pave the way for the CDC to formally approve a vaccine before the weekend.
American government bought After all approvals are obtained, more than 170 million doses of both vaccines will be available (an additional 4 million doses will be ordered for children if approved at a later date).
But the expected arrival of an updated vaccine has sparked debate among infectious disease experts and others.
Some criticized the new booster as not yet tested in humans and said they would wait to get the updated booster or skip it entirely. Others worry that the public will see the new vaccine as rushed, adding to the hesitancy of a public already reluctant to get another shot.
Still, many experts applaud the speed with which the newer vaccine is being developed and say the safety of a COVID-19 vaccine is well established. This transition to an updated vaccine for COVID-19 is being completed, they said, just as the U.S. updates its flu vaccine every year, adjusting the formulation of established vaccine platforms to combat new viruses or variants expected to spread.
The route to the new booster
Earlier this year, the vaccine maker provided the FDA with data for an updated vaccine against BA.1, the early dominant Omicron variant. But then the FDA asked the companies to update their vaccines to add the Omicron BA.4/5 component to create a bivalent booster vaccine — meaning it would cover both the original strain of the virus that emerged from China and newer ones BA.4 and BA.5 subvariants.
This will be the first update of the mRNA vaccine since its launch in December 2020.
FDA’s Advisory Committee on Vaccines and Related Biologics Meets with Vaccine Manufacturers Review at the end of June Data on Omicron’s specific COVID-19 vaccine candidate.
For the new booster, the FDA did not schedule another meeting of its vaccine advisory group, according to FDA Commissioner Robert Califf, MD. He noted on Twitter that “the agency is confident in the extensive discussions held in June.”
Update booster evidence
end of June, Pfizer BioNTech and ModenaSubmit to FDA Human data with the BA.1 vaccine. The companies also provided laboratory or animal data for their BA.4 and BA.5 vaccine candidates.
Both companies showed that the BA.1 vaccine elicited antibody responses to BA.4 and BA.5, but less than BA.1.
The companies also provided data showing that the updated vaccine has similar side effects to the original vaccine, such as soreness and fatigue at the injection site.
In mouse studies submitted to the FDA, Pfizer said its new enhancer increased antibody responses to all Omicron variants, including BA.4 and BA.5.
Results from human clinical trials are coming, but not anytime soon. Moderna has just completed enrollment in its BA.4 and BA.5 booster clinical trials, with results expected in the fourth quarter of 2022. Pfizer said it plans to start a trial soon.
Peter Marks, MD, director of the FDA’s Center for Biologics Evaluation and Research, told NPR Data from studies in mice suggest that the new vaccine may be 20 times more protective against Omicron than the original vaccine.
Responding to any concerns about the new vaccine’s safety data in humans, CDC Director Rochelle Walensky, MD, recently told CNBC The new footage involves very small changes in the mRNA sequence, which should not affect safety.
Infectious disease specialist weighs in
The lack of convincing data on neutralizing antibodies against BA.4 and BA.5 is a problem, said Paul Offit, MD, an infectious disease specialist and director of the Center for Vaccine Education at Children’s Hospital of Philadelphia.
“At the very least, I would like to see neutralizing antibody data for people who got this BA.4, BA.5 vaccine compared to just the monovalent vaccine and see a dramatic increase in neutralizing antibodies, a 4- or 5-fold increase,” he said. Say.
Offit also questioned which groups should get newer vaccines based on benefits, arguing that the best approach would be to target those most at risk of severe COVID-19, such as the elderly, those with severe illness or those with weakened immune systems .
“Those are hospitalized,” he said. He believes the goal of updated vaccines is to prevent serious disease.
Offit said he had been vaccinated and boosted, and had contracted a mild form of COVID-19 about 3 months ago, which he plans to skip.
Eric Topol, MD, executive vice president of Scripps Research and editor-in-chief of Medscape (WebMD’s medical specialty sister site), applauds FDA’s “aggressive and stop-gap” approach, with BA.5 vaccine available for review in just 2 months at FDA meeting After requesting this vaccine.
He noted that the quadrivalent influenza vaccine protocol is updated annually using mouse data. “But there are concerns that it will not be easy to extrapolate the SARS-CoV-2 virus to humans, which is very different from the flu,” he wrote on his online platform. Basic facts.
Another potential problem, Topol and others say, is something called imprinting, also known as the catchy but potentially misleading term for “primitive antigenic sin,” in which a person’s first exposure to the virus affects subsequent Virus response. The concern is that people may “train” their immune systems to remember the response to the first infection and, when faced with different variants (such as those targeted by new boosters) poor responsiveness.
Currently, he said, “It’s an unknown, and the data is mixed.”
Will the public accept it?
Poplar also expressed concern about the public’s trust in vaccines and the possibility that people would see the new booster as an emergency job. As he also points out, only 32% of the population has received any raw booster needles.
Topol’s personal decision? He is about eight months away from his fourth injection and said he will wait to see more data. He said that was just his opinion. “Many will be hungry for new opportunities. As I said, that’s fine.”
Infectious disease expert William Schaffner, MD, professor of preventive medicine at Vanderbilt University in Nashville, is not as concerned as others about the lack of human data, citing the need to combat an expected winter surge.
“If you need a vaccine against what some people think will increase [cases in] In winter, if you wait for clinical trials, you won’t be able to get newer vaccines in time,” he said.
He also likened the adjustment of the COVID-19 vaccine to the adjustment the flu vaccine makes every year.
As for safety, “we [vaccine’s] safety and efficacy,” Schaffner said. “I think most of the public health and vaccinology community is very satisfied that these immune bridging studies we are doing show that [updated vaccines] The performance was similar to previous vaccines. “
As for safety, he said the risk of myocarditis (inflammation of the heart muscle) in some adolescents and young adults who received the second dose was lower at the booster dose. It’s reasonable to expect the updated booster to also have a lower risk of side effects, he said.
“These adjustments [with the updated vaccine] too small to compromise safety,” said Dr Katelyn Jetelina, an epidemiologist and health policy expert your local epidemiologist, Newsletter that translates science for consumers.
She recognizes concerns about imprinting, but “we now need to respond to the demands of the immune system, in [an expected] surge,” she said.
Jetelina acknowledged unknowns, such as how long newer vaccines will be effective. Because BA.5 is so new, there has been no time to analyze the vaccine in humans.In her view, “an effective vaccine is needed and Clinical data are just fantasies about this rapidly changing virus. “
As for experts who only want to focus on those at risk of serious illness, she said any progress that helps reduce the risk of infection is important: “If we don’t stop transmission, we can’t stop serious disease and death. Even if we can’t stop it completely Spread, even at 50 percent, that still helps a lot.”
She plans to get updated boosters.