August 31, 2022 – COVID-19 booster vaccines targeting the Omicron BA.4 and BA.5 subvariants that currently dominate the United States could be available in the coming days, but their arrival is fraught with controversy .
The FDA today granted emergency approval to Pfizer and Moderna mRNA boosters. Next up are meetings of the CDC’s Advisory Committee on Immunization Practices on Thursday and Friday, which could pave the way for official CDC approval of the vaccines before the weekend.
The US government has already bought more than 170 million doses of the two vaccines will be ready to use after all approvals are in place (with an order of 4 million additional doses for children, if approved later).
But the expected arrival of the updated vaccines has sparked debate among infectious disease experts and others.
Some have criticized the fact that the new boosters have not been tested on humans, saying they will wait to get the updated booster or skip it altogether. Others worry that the public will view the new vaccines as rushed, adding to the hesitation of an already reluctant public to get another chance.
Still, many experts applaud the speed with which the updated vaccines have been developed and say the safety of the COVID-19 vaccines is well established. They say this move to update vaccines for COVID-19 is being done much like the US updates its flu vaccine annually, adapting the formula of an established vaccine platform to fight new viruses or variants that are expected to circulate.
The route to the new boosters
Earlier this year, vaccine makers gave the FDA data on an updated vaccine targeting BA.1, the Omicron variant that was previously dominant. But then the FDA asked the companies to update their vaccines to add an Omicron BA.4/5 component, to create a vaccine that’s a bivalent booster — meaning it’s both the original strain of the virus that emerged from China will cover as the newer BA.4 and BA.5 sub-variants.
This will be the first update to the mRNA vaccines since they became available in December 2020.
The FDA’s Advisory Committee on Vaccines and Related Biologics met with vaccine makers in late June to review data on Omicron-specific COVID-19 vaccine candidates.
For the new boosters, the FDA has not scheduled another meeting of its vaccine advisory panel, according to FDA Commissioner Robert Califf, MD. He noted on Twitter that “the agency is confident in the extensive discussion held in June.”
Evidence on updated boosters
The end of June, Pfizer BioNTech and modernapresented the FDA with human data on the BA.1 vaccine. The companies also presented laboratory or animal data on the BA.4 and BA.5 vaccine candidates.
Both companies showed that the BA.1 vaccines caused antibody responses to BA.4 and BA.5, but lower than those for BA.1.
The companies also presented data showing that the side effects of the updated injections were similar to those of the original vaccine, such as injection site pain and fatigue.
In mouse studies submitted to the FDA, Pfizer said its new booster increased the antibody response to all Omicron variants, including BA.4 and BA.5.
Results of clinical trials in humans are coming, but not soon. Moderna has just completed enrollment of its BA.4 and BA.5 clinical booster study, with results expected in Q4 2022. Pfizer said it plans to start a trial soon.
Peter Marks, MD, director of the FDA’s Center for Biologics Evaluation and Research, said: NPR that the data from the mouse studies suggest that the new vaccines may be about 20 times more protective against Omicron than the original injections.
In response to concerns about safety data in humans from the new vaccine, CDC Director Rochelle Walensky, MD, said: recently told CNBC that the new shots involve very small changes in the mRNA sequence and that this should not affect safety.
Infectious disease experts weigh in
The lack of convincing neutralizing antibody data against BA.4 and BA.5 in humans is a problem, says Paul Offit, MD, an infectious disease expert and director of the Vaccine Education Center at Children’s Hospital in Philadelphia.
“What I would at least like to see is neutralizing antibody data in people who received this BA.4, BA.5 vaccine compared to the monovalent vaccine alone and a dramatic increase in neutralizing antibodies, a 4 or 5 -fold increase,” he says.
Offit also questions which groups should get the updated vaccine based on benefit and believes the best approach is to target those most at risk for severe COVID-19, such as older adults, people with serious medical conditions or people with weakened immune systems.
“Those are the ones who are hospitalized,” he says. He sees the goal of the updated vaccine as preventing serious illness.
Offit, who says he has been vaccinated and boosted, and had a mild COVID-19 infection about 3 months ago, plans to skip this booster.
Eric Topol, MD, executive vice president of Scripps Research and editor-in-chief of Medscape (WebMD’s sister site for medical professionals), praised the FDA’s “aggressive and expedient” approach, with a BA.5 vaccine available for review for just 2 months after the FDA meeting calling for such a vaccine.
He pointed out that mouse data is used every year to update the quadrivalent flu vaccine program. “But there is a concern that extrapolating mouse to human for SARS-CoV-2, a virus very different from the flu, is not so easy,” he wrote on his online platform. Basic truths.
Another potential concern, say Topol and others, is something called imprinting, also known by the catchy but potentially misleading term “original antigenic sin,” where a person’s first exposure to a virus has an effect on a later one. response to similar viruses. The concern is that people may “train” their immune systems to remember the response to the initial infection and be less able to respond to future infections when faced with different variants, such as those targeted by the new boosters.
For now, he says, “it’s an unknown, the data is mixed.”
Will the public accept it?
Topol has also expressed concerns about public confidence in the vaccine and the likelihood that people will view the new boosters as a rush job. As he also noted, only 32% of the population has had one of the original booster shots.
Topol’s personal decision? He is about 8 months away from his fourth shot and said he will wait to see more data. He said that’s just his perspective. “Many will be eager to get the new shot. Like I said, that’s fine.”
Infectious disease expert William Schaffner, MD, a professor of preventive medicine at Vanderbilt University in Nashville, isn’t as concerned as others about the lack of human data, citing the need to combat the expected winter wave.
“If you need a vaccine to fight what some think is an increase in [cases in] winter, you won’t have an updated vaccine in time if you’re waiting for a clinical trial,” he says.
He also compares the adaptation of the COVID-19 vaccine with what is done annually with the flu vaccine.
Regarding safety: “we know a lot about the” [vaccine’s] safety and effectiveness,” says Schaffner. “I think the majority of public health and vaccinology communities are very pleased that we are doing these immune-bridging studies showing that [updated vaccines] comparable to previous vaccines.”
As for safety concerns, he says the risk of myocarditis (inflammation of the heart muscle), which occurred in some teens and young adults with the second dose of the vaccine, was lower with the booster dose. He says it’s reasonable to expect the updated booster to carry a lower risk of that side effect as well.
“These adjustments [with the updated vaccine] are so small that it doesn’t affect safety,” said Katelyn Jetelina, PhD, an epidemiologist and health policy expert. Your local epidemiologist, a newsletter that translates science for consumers.
She acknowledges concerns about imprinting, but “we need to respond to the needs of our immune system now, in the midst of time. [an expected] flood,” she said.
Jetelina acknowledges the unknowns, such as how long the updated vaccine could be effective. Because BA.5 is so new, there has been no time to analyze the vaccine in humans. According to her “demand an effective vaccine” and clinical data is just a fantasy against this rapidly changing virus.”
As for experts who want to focus only on those at risk for serious illness, she says any advances that help reduce the risk of infection are important: “We can’t stop serious illness and death if we don’t stop transmission. Even if we don’t stop the transmission perfectly, even if it’s 50%, that still helps a lot.”
She plans to get the updated booster.