(CNN) Vaccine makers are preparing for a next possible phase of the Covid-19 vaccine rollout: booster doses.
The US Food and Drug Administration on Thursday authorized third doses of both the Pfizer/BioNTech or Moderna coronavirus vaccines for certain immunocompromised people: solid organ transplant recipients or "those who are diagnosed with conditions that are considered to have an equivalent level of immunocompromise."
The US Centers for Disease Control and Prevention has signed off on the authorization and now recommends an additional dose of vaccine for these certain people.
But these doses will be considered part of the initial vaccination series for people who have not mounted an adequate immune response. A booster dose is something different. It helps refresh a waning immune response, or helps the body fight an evolving pathogen.
The companies Pfizer and BioNTech said Monday they have submitted data from a Phase 1 study to the FDA supporting the use of a third, or booster, dose of their Covid-19 vaccine. The data showed that the booster dose elicited a significantly higher antibody response against the initial strain of the coronavirus, as well as against the Delta and Beta variants, compared to what was seen among people who got two doses.
"The data we've seen to date suggest a third dose of our vaccine elicits antibody levels that significantly exceed those seen after the two-dose primary schedule. We are pleased to submit these data to the FDA as we continue working together to address the evolving challenges of this pandemic," Albert Bourla, Pfizer's chairman and chief executive officer, said in the announcement.
And many Americans who aren't now eligible for an additional shot are wondering when it will be their turn.
The CDC said immunocompromised people are more likely to get breakthrough infections than people with healthy immune systems, and the recommendation on Friday allows certain immunocompromised people to get a third dose of Covid-19 vaccine.
"This EUA is intended to be for people with moderate to severe immunosuppression and not persons with chronic conditions for which there might be mild associated immunosuppression," the CDC's Dr. Amanda Cohn told the meeting of the Advisory Committee on Immunization Practices.
The third doses were recommended for immunocompromised people as young as 12, who are included in Pfizer's EUA. People as young as 18 can get a third dose of Moderna's vaccine. The CDC urges people to get the same vaccine they got originally.
There's not enough data to discuss the possibility of an extra dose of Johnson & Johnson's one-shot Covid-19 vaccine, the FDA said.
The CDC said patients and doctors should decide who needs an extra dose and what the timing of that dose should be. No prescription or doctor's note will be needed -- people must attest to their need for the third dose -- and third doses are already available at major pharmacies and doctors' offices.
Covid-19 vaccine boosters are not currently needed for the general US population, but the administration is checking the data daily and will be ready if that changes, US Surgeon General Dr. Vivek Murthy said Thursday.
"We're trying to understand if there's a decrease in protection that's manifesting as a significant increase in breakthrough infections, particularly breakthrough hospitalizations and deaths," Murthy told CNN's Erin Burnett.
Murthy said the administration is looking at data from pharmaceutical companies, private health care systems and other countries, including the UK, Israel and Canada.
"We look at that data very regularly, closely. When we see the threshold met, that's when we'll recommend boosters for additional people," Murthy said. "That's an if question. It's a when question, and the data is going to drive our decision on that."
However, the Biden administration is expected to lay out a Covid-19 vaccine booster strategy for all vaccinated Americans in September -- with possible details on a phased rollout, starting with the most vulnerable.
National Institutes of Health Director Dr. Francis Collins acknowledged on Fox News Sunday that boosters may be needed "maybe beginning first with health care providers, as well as people in nursing homes and then gradually moving forward."
The US can look to Covid-19 vaccination in Israel for an idea of what may need to be considered a month or so in the future, Andy Slavitt, former White House Covid-19 adviser, said Thursday. Israel has authorized Covid-19 vaccine booster doses for adults older than 50, becoming one of the first countries in the world to make such a move.
"Israel began their vaccination process a little bit ahead of us, so I think in many respects, we've been looking to them -- and to a certain extent, the UK -- for what we can expect, as well as the people who participated in the original clinical trials of the vaccines in 2020," Slavitt told CNN's Anderson Cooper on Thursday. "Those three things together, generally speaking, give us a sense of what to predict for the future."
Some researchers and health officials suspect antibodies against coronavirus produced through the vaccines may diminish over time -- possibly after a year or more -- and may not protect as well against coronavirus variants that could emerge.
In July, Israel's health ministry said in a statement that it had seen efficacy of Pfizer's vaccine drop from more than 90% to about 64% as the B.1.617.2 or Delta variant spread.
That might mean a vaccinated person would need a booster dose of vaccine to stay protected against the original coronavirus strain and newly emerging variants -- including the Delta variant -- in a way similar to how a tetanus booster is recommended every 10 years or different flu vaccines are recommended each year.
In the case of Covid-19 vaccines, it remains unknown for how long immune protection lasts, but vaccine developers and health officials know it may not be forever -- and that emerging variants could evade immunity.
"There is a little nuance with Covid-19 vaccines," Dr. William Moss, professor and executive director of the International Vaccine Access Center at Johns Hopkins Bloomberg School of Public Health, told CNN in May.
While typical booster doses use the same vaccine formula someone previously received to remind the immune system about immunity to a pathogen, Moss said, any future boosters for the Covid-19 shot could use altered vaccine formulas.
For instance, the companies Pfizer and BioNTech said in a statement that while a third dose of their coronavirus vaccine "has the potential to preserve the highest levels of protective efficacy against all currently tested variants including Delta, the companies are remaining vigilant and are developing an updated version of the Pfizer-BioNTech COVID-19 vaccine that targets the full spike protein of the Delta variant."
Whether booster coronavirus vaccine doses are modified or not, missing a booster dose -- if one is recommended in the future -- could leave someone less protected against Covid-19.
"A person who skipped a booster is placing themselves at higher risk of getting infected, and getting disease from the SARS-Coronavirus-2, but I would also expect that they're going to have some partial immunity and so they may be protected against more severe disease," Moss said in May. SARS-CoV-2 is the virus that causes Covid-19.
"They're just at higher risk of infection and disease than someone who got the booster, but they have more immunity than someone who was never vaccinated."
Scientists are also currently investigating whether it makes a difference if someone gets the same type of vaccine as a booster as the original dose administered.
Then there is the question of mixing and matching doses.
Researchers in the United Kingdom reported in May that people who got mixed doses of coronavirus vaccines -- receiving a different vaccine type as a second dose than the first dose -- appear to be more likely to experience mild side effects such as fever, chills, fatigue or headache.
But the side effects following mix-and-match vaccinations were short-lived and there were no other safety concerns, the researchers reported in the Lancet medical journal.
All three companies that currently have authorized coronavirus vaccines in the United States -- Pfizer, Moderna and Johnson & Johnson -- are investigating the potential use of boosters.
"The data that I see coming, they are supporting the notion that likely there will be a need for a booster somewhere between eight and 12 months," Pfizer CEO Albert Bourla told Axios in May. "But that remains to be seen and I believe in one, two months we will have enough data to speak about it with much higher scientific certainty."
The first dose of Pfizer's coronavirus vaccine in the United States was administered on December 14, 2020.
Moderna is currently conducting booster shot trials too.
The fight against the coronavirus pandemic is expected to continue through next year due to the emergence of variants, Dr. Stephen Hoge, president of Moderna, said during an earnings call in early May.
"We think this is just the beginning," Hoge said. "Therefore, we're committed as a company to make as many updates to the vaccine, to add as many variants as we think are necessary, to ensure that when people receive a booster, it provides the broadest immune protection against the widest range of variants."
Johnson & Johnson is also looking into the potential for boosters, the company told CNN.
Johnson & Johnson's coronavirus vaccine, along with Pfizer's, Moderna's, and four others, are being tested as seasonal boosters in a study called Cov-Boost being conducted by the UK's National Institute for Health Research and the University of Southampton.
The biotechnology company Novavax has developed a coronavirus vaccine that its chief executive officer Stanley Erck believes could be used as a booster shot for people who have already been vaccinated. The company plans to apply for emergency use authorization of its vaccine in the United States in the fourth quarter of 2021.
The decision to broadly use Covid-19 boosters is expected to involve two agencies -- the FDA and the CDC -- and the regulatory process to get the shots into arms could vary depending on whether the booster is the same vaccine that was originally used or is a modified version.
"So, if it's the same vaccine, my understanding is that what would have to happen is that the CDC would have to recommend an additional dose with details around when that should occur," Moss said in May.
In other words, the FDA must give authorization for the vaccines to be used in new ways outside the existing authorization. Then, the CDC advises on whether to actually use the vaccine as authorized by the FDA.
If it's a modified vaccine, "this is where things get interesting and I don't think we quite know," Moss said, but added that the regulatory process could be similar to what happens with flu vaccines each year.
"Technically, whenever a vaccine like that is modified, it's often considered a new vaccine and has to go through the whole process again. But there is a precedent, obviously, with influenza virus vaccines, not to do that," Moss said. "So, the influenza vaccine each year doesn't have to go through a large Phase 3 trial."
That's because the vaccine technology stays the same, and the only change is the strain of flu virus that the vaccine targets.
There is no definite way to know someone needs an additional dose of coronavirus vaccine -- but so far, studies on booster doses have measured antibody levels.
Cancer patients who receive the Covid-19 vaccine, for example, are less likely to develop protective antibodies, according to two studies published this week in the journal JAMA Oncology. Antibodies are proteins the body makes to fight infection.
Yet the researchers noted that the test used to detect Covid-19 antibodies does not provide information about T-cell-based immunity or clinical outcomes related to potential Covid-19 infection. T-cells and B-cells are other components of the immune system with immune memory that can protect the body against infection.
In one of those studies, researchers in Israel followed up on initial findings showing anti-spike Covid-19 antibody levels were significantly lower among cancer patients 5.5 weeks after the second dose of an mRNA Covid-19 vaccine, compared to non-cancer patients.
The team looked at 95 cancer patients and 66 control patients from their initial analysis about four months after their second vaccine dose. About 87% of cancer patients and 100% of patients in the control group showed anti-spike antibodies, and antibody levels were still significantly lower in the cancer patients. The researchers noted that the median antibody level for both groups decreased over time.
Separately, among organ transplant recipient patients in a Johns Hopkins University study who had no measurable antibodies after receiving two doses of vaccine, one-third of them saw a rise in antibodies after a third dose -- and among those with low antibody levels after two doses, all of them saw an increase after a third dose.
Dr. Dorry Segev, an author of the study and founder of the Epidemiology Research Group in Organ Transplantation at Johns Hopkins University, told CNN in June that it's unclear what antibody level provides protective immunity. "We don't know if you need the same off-the-charts level of antibodies that people with normal immune systems have," he said.
Some experts predict that a coronavirus vaccine booster dose might be needed annually -- but despite such predictions, Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, has said that the bottom line is no one knows yet.
Still, the US is prepared for the possibility, Fauci said during a White House Covid-19 Response Team briefing in August.
Fauci said he believes eventually everyone will need a booster to maintain full protection from the vaccine.
"We are evaluating this on a day by day, week by week, month by month basis, looking at any of a number of studies, both international and domestic." he said.
He added that if it looks like immunity is waning, or a variant is evading the protection offered by current vaccines, then health officials will be ready to recommend boosters.
Eventually, it's possible that a booster dose of Covid-19 vaccine might just be part of the completion of immunization, not an annual requirement to revaccinate, Dr. Peter Marks, director of the FDA's Center for Biologics Evaluation and Research, said last week.
"I don't think that we want to think that these vaccines have somehow failed us," Marks said at a discussion hosted by the Covid-19 Vaccine Education and Equity Project.
"It may simply be that to get the kind of really good immunity against Covid-19 that we get with some other vaccines, it may take a series of three vaccinations, much the same way that hepatitis B for adults and multiple childhood vaccination primary series, you need to get a vaccination, you know, 0, 1; or 0, 2 and 4; or 0, 2 and 6 months."