Third booster doses of the Pfizer-BioNTech COVID-19 vaccine are currently available for immunocompromised Americans, and will soon be available to people 65 and older and those at high risk of severe disease.

All three COVID-19 vaccines available to Americans have been shown to virtually eliminate the risk of severe illness or death due from COVID-19, but reports of vaccinated people contracting and spreading the virus – while still uncommon – have federal health officials calling for some Americans to roll up their sleeves again.

As booster shots become increasingly available, we sought answers to some frequently asked questions from two leading vaccine researchers: Dr. Mark Mulligan, the director of the Vaccine Center at NYU Langone Health, and Dr. Florian Krammer, the Principal Investigator of the Sinai-Emory Multi-Institutional Collaborative Influenza Vaccine Innovation Center.

Clinical trials are underway for two different types of booster shots.

“One is a third shot or an additional shot of the initial authorized vaccines, whether [Johnson & Johnson], Pfizer, Moderna,” Dr. Mulligan explains.

This kind of booster dose is already available to Americans with compromised immune systems. A booster of the Pfizer COVID-19 may soon be allowed in people 65 years old and older and others considered high risk for severe illness. 

“The second kind,” continues Mulligan, “would be a new vaccine that matches a variant of concern.”

Drug companies are testing boosters that target specific variants, including Pfizer and BioNTech, who announced earlier this year that they are "developing an updated version" of their vaccine "that targets the full spike protein of the Delta variant."

Research shows there may be benefits to mixing vaccine types — for example giving a Pfizer booster to someone who originally got a J&J shot. 

Dr. Mulligan pointed to data out of the United Kingdom, where researchers have tried this mix and match approach.

“They have reported that it's safe and tolerable and that they see, sometimes, stronger immune responses,” he added.

Dr. Krammer explained that the mixing of vaccine types can stimulate different parts of the immune system. 

This approach has been put to the test before using experimental vaccines for viruses like HIV and influenza.

“And there it works really, really nice," Dr. Krammer said. "It works better than giving the same vaccine twice." 

While the research may be promising, the FDA and CDC have yet to weigh in on this strategy, but active clinical trials are underway. 

If mixing vaccines isn’t an option, experts say getting another dose of the primary vaccine received may be necessary if there is waning immunity.

“The other reason,” says Mulligan, “would be that a variant might appear that was more difficult for the immune system to handle. And so a higher level of immunity might be able to handle it.”

Experts say the vaccines offer strong protection – even against the highly contagious delta variant, which has driven a recent surge in COVID cases – but recent studies have found that protection may wane over time, making some people susceptible to severe disease. 

An additional dose can help boost the immune system’s defenses, increasing the level of protection. 

“Older individuals and those with serious comorbid conditions were among the first to be vaccinated," Dr. Mulligan explained. "So they're now eight months out or seven, six, seven, eight months out. And this is the time frame that the government has suggested would be a sort of a sweet spot to give a booster before we start seeing a lot of deaths. We're already starting to see those deaths, I think, in the older individuals and in compromised hosts.”

Experts say you would need a crystal ball to answer this question. It depends on whether more people are vaccinated, limiting the spread of the virus, and preventing new variants from emerging. 

Either way, Krammer points to research showing that the immune system will offer some level of protection for years.“Even if your immunity wanes over time a little bit and you might get reinfected, these immune cells come back very quickly because they remember the virus, even if it's a variant,” he says. “So even years after vaccination or infection, it's very likely that you get then infected with SARS-COV-2 or one of the variants, that it is very mild or even asymptomatic.”

It’s unlikely, Krammer says, that we will lose our immunity entirely. The question is whether it will remain strong enough to protect you from severe illness. 

People with weakened immune systems were the first to gain access to booster shots.

Studies have shown that depending on the health condition, the original vaccine doses may not be enough to trigger a protective immune response. In some cases people have even died from exposure to COVID-19 after receiving the vaccine.

“There's a lot of immunocompromised people out there” says Krammer, “and we need to make sure that they are protected as well.”

Research into the need for boosters continues as new COVID variants emerge… Experts say what is needed most right now - is for more people here and around the world, to be vaccinated.