August 31, 2022 – COVID-19 booster vaccines targeting the Omicron BA.4 and BA.5 sub variants currently dominant in the United States may be available in the next few days, but their arrival comes with some controversy.
Food and Drug Administration Granting emergency approval to mRNA enhancers from Pfizer and Moderna today. Next is the CDC’s Advisory Committee meetings on immunization practices on Thursday and Friday that could pave the way for an official CDC endorsement of vaccines before the weekend.
US government Already bought Over 170 million doses of the two vaccines to be ready for use after all approvals are obtained (with an additional 4 million doses to be ordered for children, if approved later).
But the expected arrival of updated vaccines has sparked controversy among infectious disease experts and others.
Some have criticized the fact that the new boosters have not been tested in humans and have said they will either wait to get the updated booster or skip it altogether. Others worry that the public will view the new vaccines as urgent, adding to the reluctance of an already reluctant public to get another dose.
However, many experts applaud the speed with which updated vaccines have been developed and say the safety of COVID-19 vaccines is well established. They say this transition to updating COVID-19 vaccines is being done much like the US updates the flu vaccine annually, adjusting the formula of the vaccine platform established to combat viruses or new variants expected to be in circulation.
The way to the new boosters
Earlier this year, vaccine makers submitted Food and Drug Administration data for an updated vaccine targeting BA.1, the Omicron variant that was prevalent earlier. But then, the Food and Drug Administration asked the companies to update their vaccines to add the Omicron BA.4/5 component, to create a bivalent vaccine — meaning it would cover both the original strain of the virus that emerged from China and the most recent BA.4 and BA.5 sub variants. .
This will be the first update for mRNA vaccines since they became available in December 2020.
The Food and Drug Administration’s Advisory Committee on Vaccines and Related Biological Products met with vaccine manufacturers In late June to review Data on the candidate COVID-19 vaccine for Omicron.
For the new boosters, the Food and Drug Administration has not set a date for another Vaccine Advisory Committee meeting, according to FDA Commissioner Robert Califf, MD. “The agency feels confident in the intense discussion that took place in June,” he noted on Twitter.
Guide to updated boosters
It will end in June. Pfizer BioN Tech And the ModernaFDA introduced With human data on the BA.1 vaccine. The companies also provided laboratory or animal data on candidate vaccines for BA.4 and BA.5.
Both companies showed that the BA.1 vaccine elicited antibody responses to BA.4 and BA.5, but less than those of BA.1.
The companies also provided data that showed the side effects of the updated shots were similar to those of the original vaccine, such as pain at the injection site and fatigue.
In studies in mice submitted to the Food and Drug Administration, Pfizer said its new booster increased antibody responses to all omicron variants, including BA.4 and BA.5.
Results from human clinical trials are coming, but not soon. Moderna has just completed enrollment in its enhanced BA.4 and BA.5 clinical trial, with results expected in the fourth quarter of 2022. Pfizer said it plans to start a trial soon.
‘” said Peter Marks, MD, director of the FDA’s Center for Biological Evaluation and Research NPR Data from mouse studies suggest that the new vaccines may be about 20 times more protective against Omicron than the original vaccines.
In response to any concerns about the safety data in humans from the new vaccine, CDC Director Rochelle Walinsky, MD, Recently for CNBC that the new snapshots include very small changes in the mRNA sequence and this should not affect safety.
Infectious disease experts weigh in
The lack of convincing data for antibodies against BA.4 and BA.5 in people is problematic, says Paul Offit, MD, an infectious disease expert and director of the Vaccine Education Center at Children’s Hospital of Philadelphia.
“At least, what I’d like to see is neutralizing the antibody data in people who got the BA.4, BA.5 vaccine compared to getting the monovalent vaccine only and to see a significant increase in neutralizing antibodies, a 4 or 5-fold increase,” he says. .
Offit also questions which groups should get the updated vaccine based on benefits and thinks the best approach is to target people who are most at risk of severe COVID-19, such as the elderly, people with serious medical conditions, or those with a weakened immune system. immune system.
“These are the ones who are hospitalized,” he says. He believes that the goal of an updated vaccine is to prevent a serious disease.
Offit, who says he was vaccinated and boosted, and had a mild COVID-19 infection about 3 months ago, plans to skip that boost.
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 appropriate” approach, with the BA.5 vaccine available for review only two months after an FDA meeting requesting such a vaccine. .
He noted that mice data are used every year to update the quadrivalent influenza vaccine program. “But there is a concern that it is not easy to extrapolate a mouse to a human for SARS-CoV-2, which is a very different virus from influenza,” he wrote online on his online platform. Earth facts.
Another potential concern, Topol et al. say, is something called imprinting, also known by the catchy but potentially misleading term “original sin of antigen,” with a person first being exposed to a virus that has an effect on a subsequent response to similar viruses. The concern is that people may “train” their immune system to remember the response to the first infection and be less able to respond to future infections when faced with different variables, such as those targeted by new enhancers.
For now, he saysAnd the “It’s unknown, the data is mixed.”
Will the public accept it?
Topol also expressed concern about public confidence in the vaccine and the chance that people will view the new boosters as an urgent task. As he also pointed out, only 32% of the population got any of the original booster shots.
Topol’s personal decision? It’s been about 8 months since the fourth shot and he said he’ll wait to see more data. He said that was just his point of view. “Many will be eager to get the new shot. Like I said, that’s fine.”
Infectious disease expert William Schaffner, 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 surge.
“If you need a vaccine to combat what some think it would be an increase [cases in] In the winter, you won’t have a timely updated vaccine if you wait for a clinical trial.
It is also like adjusting the COVID-19 vaccine to what is done annually with the flu vaccine.
As for safety, “We know a lot about [vaccine’s] Safety and efficacy,” Schaffner says. “I think the majority of the public health and vaccinology communities are very satisfied that we are doing the immunological bridge studies that show [updated vaccines] It was performed similarly to previous vaccines.”
As for safety concerns, he says the risk of developing 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 an updated booster to also have lower risks for this side effect.
These modifications [with the updated vaccine] Catelyn Getilina, an epidemiologist and health policy expert who publishes Your local epidemiologist, A newsletter that translates science for consumers.
She understands the concern about the footprint, but “we need to respond to the needs of our immune system right now, in the midst of [an expected] She said.
Jetelina acknowledges unknowns, such as how long an updated vaccine can be effective. Since the BA.5 vaccine is so new, there has been no time to analyze the vaccine in people. In her opinion, “they demand an effective vaccine.” And the Clinical data is just fiction against this rapidly changing virus.”
As for experts who want to focus only on those at high risk of serious disease, she says any progress that helps reduce the risk of infection is important: “We can’t stop severe disease and death if we don’t stop transmission. Even if we don’t stop transmission completely, even If it’s 50%, it still helps a lot.”
Planning to get the updated booster.