To Avoid ‘Booster Fatigue,’ Future COVID-19 Vaccine Doses Should Target Severe Disease
Executive Summary
CDC’s ACIP members say goal for now should not be preventing infection. FDA’s Doran Fink notes that the agency will act diligently on EUA of vaccines in children under five once it receives submissions, cites the complexity of reviewing Novavax’s EUA request for its vaccine.
The Centers for Disease Control and Prevention convened its Advisory Committee on Immunization Practices to get their input on the best approach to COVID-vaccine booster shots. ACIP members emphatically agreed that the goal for future doses of vaccines should be to prevent severe disease and death rather than prevention of infection.
“We should not chase the rainbow” of hoping currently available vaccines “could prevent infection, transmission and even mild disease because we’ve learned that that is just not possible,” Sarah Long, professor of pediatrics, Drexel University College of Medicine, said. “It probably is only possible for weeks and maybe not even so great with booster doses.”
David Kimberlin, liaison representative from the American Academy of Pediatrics and Red Book editor, asserted that now is the time to convey to the American public “with a more consistent voice than perhaps we’ve done in the past,” that we want vaccines to prevent severe disease, hospitalizations and death.
“The overwhelming majority of Americans are not immunocompromised. Let’s give them what the goal is,” he said, which is going to be a two-dose primary series, plus one booster, and at least right now for this upcoming year an annual booster.
Beth Bell, clinical professor, University of Washington, said she is “very concerned about booster fatigue” and people losing confidence in the vaccination program.
“I think it’s relatively obvious that a vaccination program that’s going to require boosting large proportions of the population every four to six months, it’s really not sustainable and probably not something that most people want to participate in, she said. “If the ACIP is going to be asked to consider additional doses for immunocompetent people, the incremental benefit is going to be likely not greater, and probably less.”
Flexibility In Vaccine Rollout
The US Food and Drug Administration authorized a second booster of Pfizer Inc./BioNTech SE’s and Moderna, Inc.’s mRNA COVID-19 vaccines for individuals 50 years and older and for immunocompromised individuals last month. (Also see "US FDA Bypasses Adcomm In Authorizing Second COVID Booster Because Decision ‘Straight-Forward’" - Pink Sheet, 29 Mar, 2022.)
ACIP was not asked to vote on or make recommendations for the use of booster shots but rather to discuss the primary goal for future doses, the data that would be important to review, and other considerations.
"We're getting smaller incremental benefits with each additional dose from these vaccines." – CDC's Amanda Cohn
Sara Oliver, a medical officer at CDC’s National Center for Immunization and Respiratory Diseases, presented a framework for evaluating future doses of COVID-19 vaccines. She said vaccine policy with a goal focused on prevention of all infection would likely require timing of vaccine rollout just prior to any increase in COVID cases, which could be difficult to predict.
“We know that the prevention of severe disease is more durable. Vaccine policy with a goal focused on the prevention of severe disease would potentially allow more flexibility in the timing of future vaccine rollout,” Oliver said.
Summing up the presentations on vaccine efficacy in booster doses, CDC’s Amanda Cohn, chief medical officer of the National Center for Immunization and Respiratory Diseases, said “we’re getting smaller incremental benefits with each additional dose from these vaccines.”
Need To ‘Communicate With One Voice’
While not an immediate goal, panel members expressed interest in having vaccines that prevent infection at some point.
“I am hoping for a future set of vaccines that can protect us against infection vectors out there,” committee chair Grace Lee, professor of pediatrics, Stanford University School of Medicine, said.
Lee also noted the need to have a shared vision and goal. “It does seem like at some points we’ve had different objectives,” she said, adding that she was referring to the federal and state response to dealing with COVID-19 infection.
“The other challenge we have is that we need to communicate with one voice,” she said. “I think that will go a long way in terms of helping the public understand the nuance and scientific complexity and the uncertainty that’s in front of us today.”
Oliver also emphasized the importance of having COVID vaccine policy that is simple. She said that calling a vaccine an annual booster may be easier to communicate than referring to the total overall number of doses, such as a second or fourth dose.
Manufacturers Should Be Cautious
Michael Hogue, a liaison representative from the American Pharmacists Association and the dean of Loma Linda University School of Pharmacy, commented on the need for manufacturers to be careful about what they say about their vaccines. He noted that the FDA has restrictions on what manufactures can say when a vaccine is approved under a biologics license application.
“I think we are in a bit of a precarious situation here where we have the vaccine manufacturers who have done outstanding work in creating novel products that have brought us out of a large portion of the serious phase of the pandemic,” he said. “But we also have to balance that with ensuring that we don’t get the cart too far before the horse and the manufacturers aren’t driving the vaccine policy discussions beyond where they should go and creating confusion in the American public that could detract people away from their confidence in the overall vaccine program and strategy.”
“So I do believe there’s a responsibility there to the manufacturers, especially when there’s BLA in place, to be cautious about what they say and for the FDA to hold them accountable for that and I hope they will do so,” he stated.
A similar concern was raised last week at the FDA’s Vaccines and Related Biological Products Advisory Committee meeting, which focused on considerations in deciding COVID-19 vaccine strain composition. Members told FDA that the agency, not vaccine manufacturers, should dictate the conversation around variants and reformulations. (Also see "COVID Vaccines: US FDA Should Play More Activist Role In Development Of Modified Formulations" - Pink Sheet, 7 Apr, 2022.)
FDA To ‘Work Diligently’ On Applications For EUA In Younger Children
During the public comment portion of the meeting, speakers called for immediate action in authorizing Pfizer/BioNTech and Moderna’s vaccines in children younger than five.
Pfizer announced in February that it had initiated a rolling submission for emergency use authorization of a two-shot vaccine in children six months through four years of age. The FDA cancelled an advisory committee that was to consider the two-dose data until the agency could review data on the impact of a third dose. (Also see "‘Don’t Make Promises Until You Have The Data’: FDA Gamble On Speeding Up COVID Vax In Kids Flops" - Pink Sheet, 11 Feb, 2022.)
On 23 March, Moderna announced positive interim data from a Phase II/III study of its vaccine in children six months to under six years of age. The company said it would be submitting a request for authorization of a two-dose primary series of the vaccine in this age group.
Following public comments, FDA’s Doran Fink, deputy director-clinical, Division of Vaccines and Related Products Applications, gave an update on EUA of COVID-19 vaccines for younger children.
“We know that many parents and caregivers and healthcare providers are anxious to have COVID vaccines available in this age group. And I do want to reassure the committee and the public that we understand this concern. We want to have available safe and effective vaccines for all age groups who will benefit from them,” he stated.
Fink said that once FDA has received one or more submissions for emergency use authorization "we will work diligently to review data to independently verify the analyses and to bring those data to our advisory committee for discussion and consideration for regulatory action."
Fink also commented on the status of recombinant protein vaccines, noting that the agency has received an application from Novavax, Inc. for emergency use authorization of its vaccine.
“I do know that many people are anxious about the availability or potential availability of vaccines as an alternative to currently available mRNA and viral vector COVID vaccines,” he said.
“This is an incredibly complex review process that involves review of not just clinical data, but also manufacturing data that will be needed to make a determination about emergency use authorization and once we have all the data that we need to complete our review, again, we will work diligently to present those data to our advisory committee in a timely manner in order to make a decision.”
In January, Novavax submitted a request for EUA of its COVID-19 vaccine NVX-CoV2373 in individuals 18 years of age and older. It had planned to do so earlier but was delayed by chemistry, manufacturing and controls problems. (Also see "Novavax Readies COVID-19 Vaccine Request For EUA, But How Much Longer Will The Door Be Open?" - Pink Sheet, 6 Jan, 2022.)
Fink also cited the challenges of labeling vaccines under an EUA rather than under a full biologics license application. (See sidebar).