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Vaccine advisers to the US Centers for Disease Control and Prevention continue to mull over what the future of Covid-19 booster shots might look like – and they acknowledge that entirely different vaccine formulations could be needed.

At their meeting Wednesday, the members of the CDC’s Advisory Committee on Immunization Practices discussed their next steps around recommending additional booster doses of Covid-19 vaccines for the general public.

Currently, additional booster doses are recommended only for certain people with weakened immune systems and adults 50 and older.

“Policy around future doses require continued evaluation of Covid-19 epidemiology and vaccine effectiveness, including the impact of both time and variants, and the ability of doses to improve this protection,” the CDC’s Dr. Sara Oliver, an epidemic intelligence service officer with the Division of Viral Diseases, said at the meeting.

Before recommending future doses of Covid-19 vaccines, Oliver said, the committee members would need to assess the nation’s recent case counts, hospitalization rates, vaccine effectiveness – including whether it’s waning over time – and the impacts of circulating coronavirus variants.

As the virus continues to evolve, the “evolution of the Covid vaccines will be important,” including the vaccine platforms, Oliver said.

The Covid-19 vaccinations that people get in the future could be completely different formulations from what’s being given now, which is based on the original version of the virus that emerged in late 2019.

The next booster might be a new vaccine

Some companies, including Pfizer/BioNTech and Moderna, are developing variant-specific vaccines that could target whatever strain of the coronavirus is circulating when that booster might be needed. Pfizer and Moderna are working on vaccines that would specifically protect against the Omicron variant, even though it’s not clear whether one is needed.

The time needed to manufacture a vaccine – once it is decided to change or update the composition of that vaccine – also is not clear.

But for the vaccines that are now available, a decision to modify them would need to be made “at the latest by the beginning of the summer” if a vaccination campaign were to be needed in the fall, Dr. Doran Fink, deputy director of the US Food and Drug Administration’s Division of Vaccines, said at Wednesday’s meeting.

Pfizer CEO Albert Bourla has said the company is also hoping to make a vaccine that will protect against Omicron as well as all other variants of the coronavirus.

The goal is to create “something that can protect for at least a year,” Bourla told CBS in March. “And if we are able to achieve that, then I think it is very easy to follow and remember so that we can go back to really the way [we] used to live.”

Moderna announced Tuesday that its first bivalent Covid-19 booster shot candidate – which combines elements of the current vaccine with updates based on the Beta variant – induced higher antibody responses against all variants of concern than the company’s original Covid-19 booster.

Moderna has been developing updated booster candidates to target emerging coronavirus variants, and it also has monovalent (based on a single virus strain) candidates in the works.

Its first bivalent booster candidate, called mRNA-1273.211, was well-tolerated, the company said, and a preprint study posted last week to the online server Research Square found that it elicited higher antibody responses than Moderna’s current booster shot against the original coronavirus and the Beta, Delta and Omicron variants.

Moderna scientists wrote in the study that the safety profile of a 50-microgram dose of the mRNA.1273.211 booster candidate was comparable to that of the current 50-microgram dose of vaccine.

The study has not been peer-reviewed or published in a professional journal.

Despite the booster candidate’s superiority over the original vaccine, Moderna CEO Stéphane Bancel said in a news release Tuesday that a separate bivalent candidate combining the current vaccine with an Omicron-specific one is still the company’s lead candidate to possibly roll out this fall.

Two-in-one flu-Covid vaccines in development

Moderna and the biotechnology company Novavax also are working on two-in-one combination vaccines that can offer protection against both flu and Covid-19.

Novavax’s Covid-19 vaccine is not authorized in the United States, but the company submitted a request for emergency use authorization to the US Food and Drug Administration in January.

In the meantime, it continues to study the vaccine that combines its NVX-CoV2373 Covid-19 vaccine and its quadrivalent flu vaccine candidate. On Wednesday, Novavax announced that the combination vaccine was “well-tolerated” and induced an immune response among participants in a Phase 1/2 clinical trial.

Novavax scientists assessed the safety of different formulations of the vaccine as well as the immunological responses they induced. The trial data showed that the combination vaccine induced immune responses comparable to those induced when the flu vaccine and Covid-19 vaccine are given separately.

The data also showed that the safety profile of the combination vaccine was consistent with the standalone safety profiles of the flu and Covid-19 vaccines. Serious adverse events in the trial were “rare and none were assessed as being related to the vaccine,” the company said.

“We continue to evaluate the dynamic public health landscape and believe there may be a need for recurrent boosters to fight both COVID-19 and seasonal influenza,” Dr. Gregory Glenn, Novavax’s president of research and development, said in a news release. “We’re encouraged by these data and the potential path forward.”

Novavax announced that the data supports advancing the study to a Phase 2 trial, which is expected to begin by the end of the year.

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For now, the CDC’s vaccine advisers plan to continue discussions around how to “be more proactive than reactive” when it comes to the future need for Covid-19 vaccinations, Dr. Matthew Daley, chair of the committee’s vaccine working group and senior investigator at the Kaiser Permanente Institute for Health Research, said in Wednesday’s meeting.

“These are our marching orders,” Daley told his fellow committee members.

“We had plenty on our plate before, but then we want to take what we’ve heard in this meeting and take it to the work group and discuss each and every one of these issues,” he said. “Given the unpredictability of the pandemic, we’ve needed to be reactive, but I think this is a place where we can also try to be more proactive.”