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Although discussions about fourth doses are premature, research is increasingly supporting the effectiveness of three doses against the Omicron variant.
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  • The chief executive officer of Pfizer says a fourth dose of COVID-19 vaccine will be needed to head off another wave of new cases.
  • Pfizer has asked federal regulators to authorize a second COVID-19 booster shot for people 65 years and older.
  • Moderna has asked the FDA to for authorization for a second booster shot for people over the age of 18.
  • Countries such as Israel have already rolled out second booster doses to offer eligible populations four doses in total. The CDC has not yet indicated whether it will do this.

Officials at Moderna are asking for the U.S. Food and Drug Administration to authorize a second booster dose of their COVID-19 vaccine for people over the age of 18.

This comes after Pfizer officials are asking the Food and Drug Administration to grant authorization for a second COVID-19 booster shot for people 65 years and older.

Pfizer officials said research from Israel indicates that COVID-19 infections were two times lower for people who receive a second booster. In addition, rates of severe illness were four times lower for people with the second booster. The announcement comes just days after the chief executive officer of Pfizer says it appears a fourth dose of the COVID-19 vaccine will be necessary.

Albert Bourla said more variants of the novel coronavirus that causes COVID-19 are coming and additional booster shots will be necessary.

He said third doses have been effective so far in preventing serious COVID-19 illnesses, but immunity could wane in the face of new variants.

Research last fall indicated the standard two doses of a COVID-19 vaccine did not provide sufficient protection against infection with the Omicron variant, despite still offering enough protection against severe disease and death.

That scenario expedited the rollout of boosters in many countries, with vaccine-makers also announcing that they were working on variant-specific vaccines.

Although the necessity of three doses became apparent with Omicron, it’s still not clear how long that protection lasts, with antibodies waning over time.

Whether a fourth dose will eventually be needed — and if so, when and to whom it will be administered — remains largely unknown for now.

Here’s what the experts think about this possibility.

Bourla told CNBC in December 2021 that a fourth dose may be needed after preliminary research showed that the Omicron variant can undermine the antibodies generated by the COVID-19 vaccine.

In mid-December, Israel also became the first country to approve a fourth dose of COVID-19 vaccines after Prime Minister Naftali Bennett announced that the second booster would be offered to people ages 60 or older and at-risk groups.

Those eligible, which includes healthcare workers and people with weakened immune systems, can receive their second booster 4 months after their third dose.

Other states and countries have also since introduced fourth doses, such as Denmark, Sweden, Chile, and the United Kingdom.

In the United States, the state of West Virginia was one of the first to apply for permission from the Centers for Disease Control and Prevention (CDC) to start administering fourth doses to people over 50 years old, people with underlying conditions, and essential workers.

In countries such as Turkey, people who initially received two doses of CoronaVac — the COVID-19 vaccine produced by the Chinese Sinovac Biotech — have also been offered two extra doses of the Pfizer vaccine.

The four-dose exception was introduced after a 2021 study showed that the former did not offer as much protection as mRNA vaccines.

Another topic on the table is that of shortening the intervals between the second dose and booster shots.

Bourla had previously said we may need a second booster dose or a fourth dose sooner rather than later.

However, Dr. Monica Gandhi, an infectious diseases specialist with the University of California San Francisco, said that research indicates giving them too soon won’t provide as much benefit.

“The data so far does support giving boosters 4 to 6 months after the second dose, but spacing out doses actually increases immunogenicity, so I would not give sooner than 12 weeks after the last dose,” she said.

In early 2022, preliminary findings from a study carried out in Israel showed that a fourth dose of the Pfizer vaccine boosted antibodies fivefold a week after the shot was administered. However, the study was based on a few healthy individuals.

Experts mostly agree that vulnerable groups such as organ transplant recipients, cancer patients, people with chronic conditions, and people ages 65 or older are more likely to need a fourth shot than healthy individuals.

An Israeli trial, the results of which were published as a preprint on February 15, but not yet peer-reviewed, also showed that a fourth dose provided only a modest boost in protection against infection with Omicron.

An observational study comparing three doses versus four doses (also a preprint, without peer review) found the latter provided slightly higher levels of protection against infection and severe disease with Omicron.

Based on data so far, Gandhi said that a fourth dose was mostly unnecessary for the time being.

“A third dose will help increase protection but we do not yet have a rationale for a fourth dose,” she told Healthline.

At the moment, there isn’t enough data to definitively say whether everyone needs a fourth dose. However, an increasing number of reports are showing that a minimum of three doses will be crucial for Omicron.

Draft research from Oxford published in December showed that just two doses of the AstraZeneca or Pfizer vaccines offered little protection against an Omicron infection.

“[L]aboratory studies show that the Omicron variant could escape the neutralizing activity of antibodies elicited by the two-dose Pfizer vaccine substantially, although those with prior infection then vaccination had less escape,” said Gandhi.

However, she pointed out that the two-dose mRNA vaccines were still protecting people with the Omicron variant from severe disease, referring to a recent study released in South Africa.

The study found that two doses provided 70 percent protection against hospitalization with Omicron and 33 percent protection against infection. These figures were 93 percent and 80 percent for the coronavirus variant Delta, respectively.

Previous data from Pfizer showed that administering a booster dose significantly increases neutralizing antibodies, bringing the vaccine’s protection close to what two doses provided against Delta.

Similarly, an Israeli study compared people who had their second dose 5 to 6 months ago and people who had received a booster about a month ago. Researchers found that a third dose provided 100-fold protection against Omicron.

An early analysis from the United Kingdom also suggested that booster shots prevented 70 to 75 percent of people from getting any symptoms. The analysis showed a slight difference depending on whether the initial doses were from the AstraZeneca vaccine or Pfizer vaccine.

Pfizer has said it is currently working on an Omicron-specific vaccine, which could be ready for distribution as early as March 2022. Moderna, meanwhile, is conducting human trials in both the United States and the United Kingdom for its Omicron-updated booster.

A study involving mice found that an Omicron-specific booster after two doses of an mRNA-based COVID-19 vaccine offered no more protection than a standard booster.

Another study saw that while an Omicron-specific booster produced effective antibodies against infection with Omicron, it did not for other coronavirus variants.

When faced with past coronavirus variants such as Delta and Beta, Pfizer and Moderna both worked on developing tweaked vaccines but saw that current formulas provided just as much protection.

“We may or may not need to create a new vaccine tailored to new variants in the future,” said Dr. William Schaffner, an infectious disease expert at Vanderbilt University in Nashville, Tennessee.

“There’s a lot of question about whether that will be needed with Omicron, which is highly contagious. They are accumulating data to suggest that it may not be creating such severe infection. And if that’s the case, our current vaccines with boosters do provide a measure of protection against Omicron, then it’s likely we will not need an Omicron-specific vaccine. But those decisions haven’t been made.”
— Dr. William Schaffner

Gandhi said that since antibodies from vaccine-induced B cells adapt toward the variants, variant-specific boosters will likely not be necessary.

“We know now that T cells from the vaccine still work against Omicron,” she said. Additionally, “The B cells [generated by the vaccines] adapt the new antibodies they produce to work against variants.”

However, vaccines won’t be our only protection against Omicron. Antivirals could also prevent infections from progressing into severe cases. Pfizer’s antiviral pill Paxlovid and Merck’s molnupiravir are under clinical trials.

Schaffner stressed that there isn’t enough data to make an informed decision yet.

“It’s really becoming clear that if it had not been a pandemic, the initial vaccination series would have been a three-dose series. Now, there’s a difference between acknowledging that scientifically, and then defining it in a formal way what ‘complete’ vaccination entails,” he told Healthline.

Schaffner said in that sense, we are more likely to see different practices from countries.

The United Kingdom, for example, sped up its booster rollout ahead of the New Year. Since then, many other countries also introduced boosters for a majority of their populations.

“At least here in the United States, I think at the moment, we are going to remain with a two-dose receipt being the definition of complete vaccination, with an encouragement to get the booster dose,” Schaffner said.

Schaffner also emphasized that in the United States as well as other countries in the world, many people, including some adults and a larger number of kids, haven’t even received their first dose of the COVID-19 vaccine yet.

Schaffner said that annual immunization, much like with the flu vaccine, could be likely but that this idea was speculation at this point as there was not enough data.

Gandhi said that, thanks to antibodies produced by B cells from the vaccines, we may not need annual boosters.

Nevertheless, efforts are underway to create a combined influenza and COVID-19 vaccine, most notably by Moderna. Companies are now also considering creating a universal coronavirus vaccine.

“As we all look down the road, public health and infectious diseases are rather accepting of the notion that there might be, for example, annual vaccinations, or on occasion, a semi-emergent introduction of a new booster to cope with new variants. All those things are possible,” said Schaffner.

However, before such decisions are made, we may need to create a coordinated global response.

Schaffner said that although there was an existing and functioning scientific/public health structure led by the WHO to update influenza vaccines twice a year, there was still no such decision making mechanism for COVID-19 vaccines.

“[T]he administrative leadership of the countries of the world led by WHO is currently just scrambling to put together a decision making process. I think [instead of] individually countries making those decisions, we need some sort of international coherence. And that structure is being worked on right now,” he said.