FDA vaccine advisers say a plan for updating Covid-19 shots is needed


CNN
 — 

The future of Covid-19 vaccines – including when and how often booster doses might be needed – remains unclear and “complex,” according to advisers to the US Food and Drug Administration.

The FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) detailed in a meeting Wednesday how emerging coronavirus variants and the future use of Covid-19 booster shots would be approached and coordinated – and the advisers plan to continue their conversation in the coming months.

The meeting “was a good opportunity to show how complex the decision-making is going to be going forward,” Dr. Eric Rubin, editor in chief of The New England Journal of Medicine, who sits on the FDA’s VRBPAC, told CNN following Wednesday’s deliberations.

“Right now, we don’t have a good idea of what the next-generation vaccine is going to look like,” said Rubin, who is also an infectious disease specialist at the Harvard T.H. Chan School of Public Health. “And at the same time, we don’t know what the next strain is going to look like.”

As the VRBPAC panel – and other leading public health experts – work to answer some of those questions about the future, Rubin said that it is useful to get these issues “out there” now, and “start thinking about them.”

The Covid-19 vaccinations that people receive in the future could be completely different formulations than what are administered now – which are a composition based on the original version of the virus that emerged in late 2019.

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

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

“Our goal is to be able to have a single annual booster, so that we don’t have compliance issues where people don’t want to get two to three shots a winter, but they get one dose where they get a booster for corona and they get a booster for flu and RSV, to make sure that people get their vaccines,” Moderna CEO Stéphane Bancel said at the World Economic Forum in January of a single vaccine for Covid-19, influenza and respiratory syncytial virus, a common virus that causes cold-like symptoms.

Various research teams from different institutions also are working to develop a “pan-coronavirus” vaccine – one that offers protection against multiple variants of the coronavirus that causes Covid-19.

The hope is that such a vaccine could pave the way for the development of a universal coronavirus vaccine, which could head off any coronavirus and and even the menacing threat of novel coronaviruses we haven’t identified yet.

There are seven known coronaviruses that infect humans: four that cause common colds; Middle East respiratory syndrome, or MERS; severe acute respiratory syndrome, or SARS; and SARS-CoV-2, the coronavirus that causes Covid-19.

A possible universal vaccine, however, is going to take much longer to develop – likely several years – than a pan-coronavirus vaccine or so-called “multivalent” vaccine that could protect against multiple SARS-CoV-2 variants.

But while the composition of coronavirus vaccines could change in the future to target any new and emerging variants, there needs to be a “framework” for how and when such changes take place, according to VRBPAC members.

To start, the FDA would seek advice from the VRBPAC before any changes to the composition of coronavirus vaccines are made, Jerry Weir of the FDA’s Office of Vaccines Research and Review told the advisory committee in Wednesday’s meeting.

On some routine basis, “the FDA and VRBPAC would review the epidemiology of circulating SARS-CoV-2 variants in the US, the effectiveness of available vaccines in use, and the available clinical data and manufacturing concerns for modified vaccines, in order to determine whether to recommend an updated vaccine for use,” Weir said.

“There should be some thought given to a collaborative plan – this is going forward – that includes manufacturers, the FDA and other public health agencies,” Weir added.

Such a plan “would provide the necessary clinical data needed for the future vaccine composition decisions,” he said. “These plans should be developed to respond to any emerging variant that escapes protection provided by currently available vaccines.”

After all, as the coronavirus evolves, new variants are likely to emerge in the future.

In the two years since the start of the pandemic, the SARS-CoV-2 virus already has achieved about “five years” worth of virus evolution – and the virus will continue to evolve, experts told VRBPAC in Wednesday’s meeting.

When compared with various types of flu viruses, “SARS-CoV-2 so far has been evolving about twice as fast as influenza H3N2, about four times as fast as influenza H1N1, and about 10 times as fast as B/Victoria,” Trevor Bedford, a scientist at Howard Hughes Medical Institute, told VRBPAC members.

“This means that if you look here at Omicron-like viruses, in just two years’ time, since the start of the pandemic, we’ve accomplished about five years of equivalent evolution,” Bedford said. “The evolution has been remarkably fast so far.”

As the pandemic transitions into an endemic phase, “we really don’t know” whether “wildly divergent” variants of the virus will be common or rare, Bedford said. Endemic means a disease has a constant presence in a population but is not affecting an alarmingly large number of people, as typically seen in a pandemic.

Yet to respond to a fast-changing virus, coordinating the possible rollout of vaccines as variants emerge in the future remains complicated.

“We have multiple manufacturers. We are talking about some vaccines in development that might not be authorized or approved yet that could also be coming into the mix. How do we essentially unify what we’re doing for a booster?” Dr. Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research, told VRBPAC members.

“It might be better to have a unified approach with a strain selection or a variant selection, much the same as we do for influenza,” Marks said, referring to how flu vaccines are updated each year to match circulating strains. “Much like with flu, once we move to a new composition … it will also change the composition of the primary series.”

The way flu vaccines are updated each year could be a model for the future of coronavirus vaccines – but VRBPAC member Oveta Fuller, of the University of Michigan, emphasized that the nation had much more than two years to understand the flu.

“Let me remind us that we didn’t get to understand influenza in two years. It’s taken years to get to a uniform – somewhat still imperfect but also useful – process for what we do with flu,” Fuller said in Wednesday’s meeting.

“We need to remind ourselves and step back that we are very new in this pandemic, and we don’t have the answers,” Fuller said. “VRBPAC doesn’t have the answers. FDA doesn’t have the answers. The important thing here is that the public understands how complex this is.”

Even once Covid-19 transitions from a pandemic to endemic, will enough people complete their coronavirus vaccinations so that the disease stays at endemic levels – or will they grow tired of getting their Covid-19 booster doses? That is a concern that Marks expressed Wednesday.

“What really keeps me up at night is the knowledge that we can’t keep boosting and that we’re going to have vaccine exhaustion,” Marks told VRBPAC members.

“I’m talking about physical exhaustion and people not going to get boosted,” he said.

Currently, about 66% of the US population is fully vaccinated with at least their initial series – including more than 75% of adults – and about 30% have received their booster. In March, the FDA authorized second booster doses for adults 50 and older. On Wednesday, Marks called that a “stopgap” measure.

“I think we’re very much on board with the idea that we simply can’t be boosting people as frequently as we are, and I’m the first to acknowledge that this additional fourth booster dose that was authorized was a stopgap measure until we got things in place for the next potential booster, given the emerging data,” Marks said in Wednesday’s meeting.

“It was done because of the amount of harm that has come to our older population in the United States with 1 in 100 individuals over the age 65 having died in the past two years of Covid-19, so we need to protect that population,” Marks said.

“Moving forward, we will have this issue that coming into the fall season only half of the population overall – and granted it’s two-thirds of the population over age 65 are vaccinated with a third dose – but half of the population overall hasn’t received a third dose,” he added. “That means that they will not have the more durable protection.”

Marks expects to hold another meeting in early summer to discuss Covid-19 booster doses for the fall and winter, he told VRBPAC members.

Looking ahead, he said, “Our goal here is to stay ahead of future variants and outbreaks and ensure that we do our best to reduce the toll of disease and death due to Covid-19 on our population.”