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FDA Adopts Flu-Like Plan for an Annual COVID Vaccine

CDC: Bivalent shot shows efficacy against subvariants

At a Jan. 26, 2023, meeting, they outlined a new seasonal framework roughly akin to influenza vaccine creation to meet in the spring, determine the circulating SARS-CoV-2 strains of concern, and then have shots ready to begin an immunization campaign in the fall.

“We see the potential advantages for the winter seasonality with a fall [vaccine] campaign,” said Peter Marks, MD, PhD, director of the FDA Center for Biologics Evaluation and Research. “Because when do we have to worry about overwhelmed hospitals? It will be when we have influenza, RSV (respiratory syncytial virus), and, potentially, COVID all at the same time.”

Paul Offit, MD, director of the Vaccine Education Center at the Children’s Hospital of Philadelphia, voted against the bivalent booster last year, but joined the unanimous vote to move ahead with the FDA proposed plan at the January meeting.

“I certainly support this,” he said. “The reason is I think it’s important to get closer to the strains that are circulating for certain [high-risk] groups. I think our goal is to keep people out of the hospital and not let hospitals be overwhelmed. Certain things are clear: This virus is going to be with us for years, if not decades, and there will always be vulnerable groups who will be hospitalized and killed by this virus.”

The FDA has had to make some key vaccine decisions with a paucity of data, so Offit called on the Centers for Disease Control and Prevention (CDC) to provide more detailed information on COVID-19 patients.

“We need the CDC to tell us exactly who it is [who is] getting hospitalized and dying from this virus,” he said. “What are their ages? Specifically, are there comorbidities? If they are immunocompromised, in what manner are they immunocompromised? Did they recently get a vaccine, were they treated with antivirals, etc.? That has to be provided in concert with immunological data. What are the predictors, not just for antibodies, but cellular immunity? Only then can we really best make the decision about who gets vaccinated with what and when.”

The committee discussed going to a single vaccine formula that would be administered annually for most people, but the timing and number of shots were somewhat unresolved for populations at greatest risk including those older than 65 years of age, who represent most of the United States and global mortality in the third year of the pandemic.

“We’re trying to move in the direction of the influenza model,” says William Schaffner, MD, a veteran healthcare epidemiologist and public health advisor at Vanderbilt. “We update the vaccine for us [in the Northern Hemisphere] once a year. There is concurrence and agreement among the manufacturers that they will use the same basic prototype for making the vaccine. All those conversations are still going on, but we are moving in that direction.”

Schaffner is not a member of VRBPAC but praised the new approach as a way to disentangle the process.

“It certainly does simplify things for providers, and, as a consequence, for patients,” he says. “Whether this will result in any immediate increase in vaccine acceptance, I’m not sure. The people who haven’t been vaccinated to date are adults with profound reservations about the vaccine and very skeptical parents who aren’t bringing their children in.”

Devil Is in the Details

Although the effort to simplify the process drew a unanimous vote, there are a multitude of devils in the details as VRBPAC moves forward. It makes intuitive sense to vaccinate before winter, when more events and gatherings will be held indoors and people will gather for the holidays. The decision puts a flu-like process in place to add structure to the review of variants and the creation of a vaccine, but there still is the open question of whether SARS-CoV-2 will follow a seasonal pattern.

“We really don’t know yet, and I think that is what the FDA and other groups are grappling with,” says Pat Jackson, RN, BSN, CIC, president of the Association for Professionals in Infection Control and Epidemiology (APIC). “We have seen, in the last couple of years, that there have been different surges at different times of the year. We really have a good track record with flu and we know it is very seasonable. It might come a month early, it might leave a month late, but it is definitely seasonable, and it has been around a long time.”

That said, APIC is a strongly pro-vaccine group and has recommended the COVID-19 immunizations as part of good infection control and public health.

“We certainly support our industry partners and what they recommend,” Jackson says. “They are trying to get more information on how the virus is actually acting. We know it is mutating all the time.”

In that regard, while the FDA voting question cited the current bivalent vaccine containing an Omicron component as an example, things have been subject to considerable change during this pandemic. Based on the rise and fall of variants over the last three years, it remains possible that a new emergent version of SARS-CoV-2 could push Omicron aside, much as it did the Delta variant in November 2021.

Although APIC supports mandatory vaccination of healthcare workers for seasonal influenza, that is not necessarily the case for COVID-19 as the virus and the vaccine components change.

“APIC definitely supported the mandate initially of the primary vaccine series, which is the only thing that CMS (Centers for Medicare and Medicaid) requires,” Jackson says. “It was important for the health of everyone.”

The issue has come to the fore because there are increasing calls to end the current healthcare mandate enforced by CMS. A bill requiring this action passed the U.S. House, and the Biden Administration will lift the national health emergency status on May 11, 2023.

Although some healthcare facilities are requiring the current bivalent vaccine, they are not mandated to do so under the CMS rule for COVID-19 immunizations. CMS defines “fully vaccinated” for healthcare staff as those who are at least two weeks out from their primary vaccination series for COVID-19. This means staff who have received a single-dose vaccine, or all required doses of a multidose vaccine for COVID-19 are CMS-compliant two weeks later. No boosters are required.

Since it appears a federal mandate for future vaccine formulations by the FDA would face steep resistance, the decision on requiring COVID-19 shots for healthcare workers likely will fall back to the organizational and facility level.

“The decisions about how vigorously to mandate, require, or recommend the influenza vaccine clearly vary from hospital to hospital,” Schaffner says. “I think that is a quite reasonable model. I do believe that all healthcare providers wherever they work have an obligation to be vaccinated against both influenza and COVID.”

Jackson concurs, saying that, although APIC has not taken a formal position on this mandate question for COVID-19, infection preventionists support increasing vaccination rates.

“We have an ethical responsibility to do that,” she says.

Good News, Bad News

As underscored by Offit’s call for clinical data from the CDC, VRBPAC has had to make vaccine decisions that have required considerable forward thinking.

For example, the current bivalent vaccine includes the original Wuhan-1 strain and two Omicron subvariants: BA.4 and BA.5. These subvariants were on the rise when the committee met last June to decide on the vaccine components, but were disappearing rapidly by the time the vaccine was ready to administer in the fall.

As those subvariants faded, Omicron XBB.1.5 arose amid considerable concern, and now represents (as of Feb. 4, 2023) 66% of subvariants in genomic surveillance, followed by BQ.1.1 at 20% and BQ.1 at 7%.1

XBB1.5, a recombinant virus consisting of two Omicron subvariants, has a high level of immune escapability, but thus far looks to be no more virulent than its predecessors.

The good news in a recent CDC study is that the bivalent booster if anyone can be convinced to take it shows vaccine efficacy (VE) across age groups against the reigning subvariant.

“VE against symptomatic XBB/XBB.1.5-related infection was 49% among persons aged 18-49 years, 40% among persons aged 50-64 years, and 43% among those aged 65 years,” the CDC reported.2 “Findings from this study suggest that bivalent booster doses are continuing to provide additional protection against symptomatic infection for at least the first three months after vaccination in persons who had previously received two, three, or four monovalent vaccine doses, which supports recommendations to continue to increase bivalent booster coverage.”

Those figures are within coughing distance of the VE of a typical flu seasonal flu shot, which has long been promoted as a way to stay out of the hospital and the morgue.

Although the bivalent vaccine has been met with general apathy, there still are relatively high levels of existing immunity to COVID-19.

“The vast majority of the U.S. population has either been exposed to infection or vaccinated or both,” Heather Scobie, PhD, MPH, of the CDC coronavirus group, told the FDA advisory panel. “I think, in general, we’re seeing the vaccines protect pretty well for up to three months against infection, and much longer for severe disease.”

Still, as we move further into waning immunity over time, the price for refusing the bivalent vaccine and possibly future vaccines under the new FDA flu model may prove higher. Although the CDC efficacy findings may change things, as of this report, a staggering 84% of those indicated for the bivalent vaccine had not received it.3 The situation almost demanded a course change, and the move to a more flu-like vaccine model was seen as a path forward.

“Speaking with colleagues, friends, family questions I’m answering from the community, there’s so much confusion about these different formulations,” said VRBPAC member Archana Chatterjee, MD, PhD, of Rosalind Franklin University of Medicine and Science in Chicago. “I concur with my colleagues that there definitely remains a need for these vaccines and for us to do our best to get them into arms. Having vaccines is not sufficient.”

Board member Henry Bernstein, DO, MHCM, FAAP, of Cohen Children’s Medical Center in New Hyde Park, NY, said, “I think anything that results in better communication to get more of the unvaccinated vaccinated would be extremely valuable. I still have some questions, but I think this is the right direction.”

VRBPAC member Ofer Levy, MD, PhD, director of the Precision Vaccines Program at Boston Children’s Hospital, went even further in seizing the significance of the moment.

“As we have turned the corner from a pandemic phase to an endemic phase, today’s vote marks a big practical win for the American people,” he said. “This is going to really simplify things and benefit public health.”

Still, while these bouquets were being tossed, one FDA advisor tempered his praise with a dose of reality. “I think this is definitely the way to go as soon as we can figure out how to do it,” said Mark Sawyer, MD, VRBPAC member and pediatric professor at the University of California-San Diego.

Dropping the Anchor?

The new vaccine strategy will begin immediately, with a VRBPAC meeting for SARS-CoV-2 strain selection expected to occur in May. The dose amounts and timing could differ between the general public and risk groups, such as the very young, the elderly, and the immunocompromised. The recommendation by the CDC as this report was filed indicated the current bivalent vaccine for anyone aged 6 months and older.

“I think this is a very good decision to move forward with this from a programmatic and implementation perspective,” Amanda Cohn, MD, chief medical officer for the CDC vaccine task force, said at the VRBPAC meeting. “The most concerning data point that I saw this whole day was the extremely low vaccination coverage in [children] 6 months to 2 years of age and also 2 years to 4 years of age. We have to do much, much better. We really just have to focus on getting those kids vaccinated.”

One question that will inevitably come up at the vaccine component selection meeting this spring is whether and to what degree a bivalent vaccine will include the original Wuhan-1 strain, which has anchored the FDA’s overall vaccine strategy during the pandemic.

In particular, two recently published medical letters questioning the efficacy of the bivalent vaccine have raised the phenomenon of immunological “imprinting,” which Offit addressed in a published commentary.4,5

“The most likely explanation is imprinting,” he noted.6 “The immune systems of people immunized with the bivalent vaccine, all of whom had previously been vaccinated, were primed to respond to the ancestral strain of SARS-CoV-2. They therefore probably responded to epitopes shared by BA.4 and BA.5 and the ancestral strain, rather than to new epitopes on BA.4 and BA.5. This effect could possibly be moderated by immunizing people either with BA.4 and BA.5 mRNA (messenger ribonucleic acid) alone or with a greater quantity of BA.4 and BA.5 mRNA.”

Thus, Offit raises the question of whether future vaccines should continue to include the original Wuhan-1 strain, suggesting the turning point will be if and when COVID-19 eludes immunization and begins causing more severe infections and deaths. “Fortunately, SARS-CoV-2 variants haven’t evolved to resist the protection against severe disease offered by vaccination or previous infection,” Offit wrote. “If that happens, we will need to create a variant-specific vaccine.”


  1. Centers for Disease Control and Prevention. COVID Data Tracker. Variant proportions. Feb. 4, 2023.
  2. Link-Gelles R, Ciesla AA, Roper LE, et al. Early estimates of bivalent mRNA booster dose vaccine effectiveness in preventing symptomatic SARS-CoV-2 infection attributable to Omicron BA.5- and XBB/XBB.1.5-related sublineages among immunocompetent adults — increasing community access to testing program, United States, December 2022-January 2023. MMWR Morb Mortal Wkly Rep 2023;72:119-124.
  3. Centers for Disease Control and Prevention. COVID Data Tracker. Vaccinations. Feb. 8, 2023.
  4. Wang Q, Bowen A, Valdez R, et al. Antibody response to Omicron BA.4-BA.5 bivalent booster. N Engl J Med 2023; Jan 11. doi: 10.1056/NEJMc2213907. [Online ahead of print].
  5. Collier AY, Miller J, Hachmann NP, et al. Immunogenicity of BA.5 bivalent mRNA vaccine boosters. N Engl J Med 2023; Jan 11. doi: 10.1056/NEJMc2213948. [Online ahead of print].
  6. Offit PA. Bivalent Covid-19 vaccines — a cautionary tale. N Engl J Med 2023; Jan. 11. doi: 10.1056/NEJMp2215780. [Online ahead of print].