Fourth COVID Vaccine Jab Provides Little Extra Protection to Healthy Individuals – NEJM

A month after a fourth dose of the Pfizer or Moderna vaccines was administered to hundreds of people in an Israeli clinical trial, authors of the new study on the extra booster say it provides “little protection, if any, from infection by COVID-19 among vaccinated young and healthy individuals in comparison to those vaccinated with only a third dose.”

Result of the open-label study, conducted at Israel’s Sheba Medical Center, were published Wednesday evening in the New England Journal of Medicine as a correspondence.

The findings contradict statements made by Pfizer CEO Albert Bourla over the weekend that a fourth booster dose could necessary for most people, due to waning immunity. Bourla made the statement as Pfizer seeks quick US Food and Drug Administration approval of a fourth dose, effectively a second booster, for people 65 and older.

The new Sheba study included approximately 600 volunteers, among them 270 who received a fourth shot of either the Moderna or Pfizer vaccine. All of the volunteers had received three shots of the Pfizer vaccine prior to the trial.

Sheba’s Professor Gili Regev-Yochay, lead author of the study, said in a statement that COVID infection rates among four-time vaccinated individuals were only slightly lower than those in the control group. However, she added that the fourth jab did provide moderate protection against symptomatic infection among young and healthy individuals, in comparison to those who had only received three jabs.

“We found no differences, both in terms of IgG antibody levels and in terms of neutralizing antibody levels,” added Regev-Yochay, referring to the impact of the fourth jab on the study group in comparison to the control.

“It should be emphasized that the third dose is extremely important for anyone who has not yet contracted COVID-19,” Regev-Yochay stressed, “and the fourth dose is most likely important for populations with risk factors, for which a fourth vaccine would protect from serious illness.”

The NEJM correspondence, however, said that the fourth dose was “immunogenic, safe and somewhat efficacious”, adding that “our results suggest that maximal immunogenicity of mRNA vaccines is achieved after three doses and that antibody levels can be restored by a fourth dose.”  The researchers added that they observed “low vaccine efficacy against infections in health care workers, as well as relatively high viral loads suggesting that those who were infected were infectious.”

Bourla: Fourth shot ‘necessary’

The release of the data comes at an awkward time for Pfizer, after a weekend when Bourla said in an interview with CBS’s Face the Nation that a fourth COVID-19 shot would be “necessary” for most people to prevent future infection.

Pfizer CEO Albert Bourla in a CBS interview on March 13, 2022.
Pfizer CEO Albert Bourla in a CBS interview on March 13, 2022.

“Right now, the way that we have seen, it is necessary, a fourth booster right now,” Bourla said in the interview. “The protection that you are getting from the third, it is good enough, actually quite good for hospitalizations and deaths. It’s not that good against infections, but doesn’t last very long.”

While Bourla said Pfizer had submitted data on the efficacy of the fourth shot to the US FDA, the data has not yet been publicly released.

The US Centers for Disease Control and Prevention currently recommends three jabs for everyone age 12 years and up, and two shots for children between the ages of five and 11. Individuals who are immunocompromised are encouraged to get an extra dose.

Fourth dose still protects against severe infection, separate study found

A separate Israeli study published, on February 1 by the Israeli Health Ministry, offered somewhat contradictory results to the Sheba findings – although the Ministry of Health study focused only on older people.  That study, released on the pre-print biomedical website MedRXiv, found that rates of confirmed COVID-19 infection, as well as severe illness, were lower following a fourth dose, when compared to only three doses.

Specifically, the team looked at data from 1,138,681 persons aged over 60 years and eligible for the fourth dose between January 15 and 27, 2022 – the height of the Omicron wave in Israel. They compared the rate of confirmed COVID infections and severe COVID illness between those who took a fourth jab at least 12 days earlier and those who only had three doses, or alternatively those who became ill less than a week after receiving the fourth dose.

“The rate of confirmed infection was lower in people 12 or more days after their fourth dose than among those who received only three doses and those 3 to 7 days after vaccination by factors of 2.0 and 1.9, respectively. The rate of severe illness was lower by factors of 4.3 and 4.0,” the authors wrote.

‘Vaccines don’t prevent infection’

Professor Cyrille Cohen, head of the immunology lab at Bar-Ilan University, said that the findings from the Sheba study are not surprising; “the vaccines are not good enough to prevent infection, and even more so with the Omicron variant,” he said.

However, like Regev-Yochay, Cohen stressed that there is a growing body of data that shows there remains a substantial difference in the levels of protection acquired by people who are vaccinated with two doses and those who get three doses, when it comes to developing severe disease.

“Look at the ratio between people age 60 who got three doses and people that were not vaccinated and got two doses. Even with Omicron, the third dose can reduce the chance of developing severe disease by a factor of four or five and for people above 60 that number becomes 10 to 20,” Cohen said.

He also noted that a fourth dose also may help the most vulnerable, noting that today, the serious cases in Israel still tend to be older people with comorbidities or unvaccinated people.

“Based on that, a fourth dose for selected populations might demonstrate a benefit,” he said.

When asked about Bourla’s statement, Cohen said “it was not clear” and that perhaps the Pfizer CEO was referring to people receiving a shot of the Omicron-adapted vaccine, for which data has not yet been released. A multi-country clinical trial of that vaccine is now underway, including a trial arm in Israel.

“I am personally extremely curious to see those results,” Cohen said.

Image Credits: Screenshot.

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