Do Americans need boosters yet? Here are the questions the FDA will be asking

Vaccine advisers to the US Food and Drug Administration start meeting early Friday to discuss whether Americans need booster shots yet.

It’s a simple question but one that has become bogged down in politics and turf battles. It’s sometimes seemed to put the FDA’s independence at odds with a White House team eager to appear to be out ahead of an unpredictable pandemic.

On the surface, it’s a routine consideration of one company’s request for permission to start giving people a third, booster shot of its vaccine to help improve protection.

Underneath, it’s a decision that will affect all three vaccines authorized for the US market, and more that are in the pipeline. It could affect how people view vaccines, and for many, it taps into fears about disease and unknown risks.

But the questions the FDA’s Vaccine and Related Biological Products Advisory Committee will be considering are straightforward: Is immunity waning, and will boosters restore it?

Researchers have been busy answering the second question first. Multiple studies now show that a third dose of Pfizer’s or Moderna’s vaccines, or a second dose of Johnson & Johnson’s vaccine, turbo-charge the production of antibodies.

Levels of these immune system proteins – the first line of defense against infection – spike after people get a booster dose. As with other vaccines that require boosters, a longer interval of time between initial immunization and the booster seems to amplify this response.

Some initial data from Israel also indicates this boost in antibodies does translate into fewer infections among vaccinated people. It’s this data that has helped drive the enthusiasm of White House advisers, including National Institute of Allergy and Infectious Diseases Director Dr. Anthony Fauci.

The second question is a little harder to answer. Is immunity waning? Are fully vaccinated people becoming, with each day, more likely to become infected?

Again, data from Israel indicated that the longer out people were from their first round of immunizations, the more likely they were to suffer breakthrough infections.

But there is much less data about this from the United States. That’s in no small part because the US Centers for Disease Control and Prevention has not been tracking all breakthrough cases – only those serious enough to put people into the hospital or to kill them. One question VRBPAC will be asking is how much data there is indicating that immunity is starting to drop off among Americans who were among the first to be vaccinated.

There are two ways to answer that question. Most of the studies Pfizer and other groups have done to support the argument for boosters look at people’s blood – their levels of antibody protection. There’s not a lot of data yet that shows more people who were vaccinated early on are becoming infected in the US.

And the FDA has been clear that it wants US data. “Some studies may be more reliable than others. Furthermore, US-based studies of post-authorization effectiveness of BNT162b2 may most accurately represent vaccine effectiveness in the US population,” it said pointedly in briefing documents released ahead of Friday’s meeting.

Then there is a question about what vaccines are actually intended to do. Are they meant to prevent all infection, in essence creating a force field around people? Or is it, as FDA, CDC and the White House have all argued, that what vaccines are really meant to do is prevent severe disease and death?

There are very strong indications that vaccines are still doing that. As of September 7, according to the CDC’s limited tracking, 14,115 fully vaccinated people have been hospitalized with Covid-19 or died of it. That’s out of 176 million fully vaccinated people.

One reason they’re protecting against severe disease and death is the complex nature of the human immune system. Antibodies are not the only defense against infection. They may stop the virus from getting into some cells in the body, but there’s another line of defense: cell-based immunity. Cells called B cells and T cells can take longer to generate than antibodies, but they provide a longer-lived, broader defense against infection and are responsible for decreases in severe infections.

Plus, FDA has already okayed the use of third shots in the most vulnerable people – those with immune systems that have been compromised by disease or drug treatment who may not have mounted a proper response to the first doses.

So VRBPAC members will be asking questions about all of this science.

There’s a third factor. It has little to do with hard science and more to do with global public health.

The World Health Organization has been arguing long and hard against the use of booster doses in wealthier nations until most of the rest of the world is vaccinated. WHO’s concern is equity – the organization says there’s not enough evidence yet to show boosters are even needed, but it also wants to make sure that rich nations don’t get bogged down in arguing about boosters and distributing them while other countries go without a single dose of vaccine.

There’s a pragmatic angle to this argument, also. If coronavirus is circulating anywhere in the world, it can spread anywhere. And vaccination may not always protect people who argue that what happens in, say, Africa is not their problem. Because if a virus is spreading, it is mutating – and coronavirus could easily evolve into a form that resists current vaccines.