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Although discussions about fourth doses are premature, research is increasingly supporting the effectiveness of three doses against the Omicron variant. Nick Oxford/Bloomberg/Getty Images
  • Studies so far have shown that just two doses of COVID-19 vaccines may not be as effective against the Omicron variant.
  • However, data has indicated that boosting with an additional shot of the COVID-19 vaccines may restore this protection to a level similar to what the two-dose regimen provided against other variants.
  • Israel has 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.
  • Scientists stress there is not enough data to warrant a fourth dose or annual immunization at this time.

Early reports suggest the standard two doses of a COVID-19 vaccine may not provide sufficient protection against infection with the Omicron variant of the coronavirus, despite still offering enough protection against severe disease and death.

This has expedited the rollout of boosters in many countries, with vaccine-makers announcing that they’re working on variant-specific vaccines.

Although the necessity of three doses is becoming apparent, it’s less clear how long that protection lasts with antibodies waning over time.

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

Here’s what the experts think about this possibility.

Pfizer CEO Albert Bourla told CNBC 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. He also said we may need this dose sooner rather than later.

“When we see real-world data, it will determine if the Omicron is well covered by the third dose and for how long. And the second point, I think we will need a fourth dose,” Bourla said.

“With Omicron we need to wait and see because we have very little information. We may need it faster,” he added.

Despite these comments, the World Health Organization (WHO) hasn’t decided to endorse a global rollout of booster shots and has signaled that more data is needed before a decision is made.

However, in December, Israel 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 those ages 60 or older and at-risk groups.

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

Preliminary findings from a recent study carried out in Israel have shown that a fourth dose of the Pfizer-BioNTech vaccine boosts antibodies fivefold a week after the shot is administered.

Meanwhile, the state of West Virginia has said it will also apply for permission from the Centers for Disease Control and Prevention (CDC) to start administering fourth doses to people over age 50, those 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-BioNTech vaccine.

The four-dose exception was introduced after studies 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.

But 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.

At the moment, there isn’t enough data to definitively say whether we need a fourth dose. However, an increasing number of reports are showing that 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 has shown 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 those who had received a booster about a month ago. They 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. They found a slight difference depending on whether the initial doses were from the Oxford-AstraZeneca vaccine or Pfizer-BioNTech vaccine.

Based on data so far, Gandhi said that a fourth dose was unwarranted.

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

Pfizer has said it is currently working on an Omicron-specific vaccine which could be ready for distribution as early as March 2022.

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 towards 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 weapon 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, recently sped up its booster rollout, with Prime Minister Boris Johnson announcing Sunday night that they hoped to get everyone boosted by the New Year instead of the end of January.

“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.

“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.