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Only ‘marginal benefits’ from second COVID booster – Israeli study

Administering a second COVID-19 vaccine booster offers little benefit for healthy healthcare professionals, according to a study at the Sheba Medical Center in Tel-Aviv.

In this open-label, non-randomised clinical study, investigators evaluated the immunogenicity and safety of a fourth dose of the Pfizer-BioNTech or Moderna vaccine booster administered four months after the third dose of a three-dose series of the Pfizer-BioNTech vaccine.

Medscape reports that of the 1,050 eligible healthcare professionals, 154 (average age 59 years) received the fourth Pfizer dose and, one week later, 120 (average age 55 years) also received the fourth Moderna dose. For each participant, two age-matched controls were selected from the remaining eligible participants.

After the fourth dose, both messenger RNA (mRNA) vaccines increased neutralising antibody titres to titres slightly higher than those obtained after the third dose, with no significant difference between the two vaccines. At the same time, antibody levels in the control group continued to decrease.

Antibody production, limited efficacy

Both vaccines induced an increase in neutralisation of the Omicron variant and other viral strains that was similar to the response after the third dose.

The fourth dose did not lead to any significant adverse reactions in most recipients beyond mild local and systemic symptoms.

By performing weekly PCR tests, the investigators observed that 25% of participants in the control group were infected with the coronavirus versus 18.3% of participants in the group that received the Pfizer booster and 20.7% of participants in the group that received the Moderna booster.

The vaccine’s efficacy against COVID infections was 30% for the Pfizer-BioNTech booster and 11% for the booster administered with the Moderna vaccine. The efficacy in preventing symptomatic disease was 43% with the Pfizer booster and 31% with the Moderna booster.

High viral loads

Most of the infected healthcare professionals reported negligible symptoms, both among the controls and among those who received the second booster. However, viral loads were relatively high, so individuals were very likely contagious in all cases.

Small population

The main limitations of the study, which was published in The New England Journal of Medicine, are its small population size and non-randomised design. Furthermore, there was a one-week gap between the injections in the two intervention groups (Moderna and Pfizer), which could have led to potential biases. In addition, adherence to the weekly SARS-CoV-2 screening was slightly lower in the control group.

Finally, regarding positive cases, because genome sequencing was not performed, it is not certain that all of the infections were caused by the Omicron variant: “However, during the study period, Omicron accounted for 100% of the isolates,” said the investigators.

“Our data provide evidence that a fourth dose of mRNA vaccine is immunogenic, safe, and somewhat efficacious (primarily against symptomatic disease),” they concluded, adding that “our results suggest maximal immunogenicity of mRNA vaccines is achieved after three doses and that antibody levels can be restored by a fourth dose”.

Furthermore, the authors said they observed low vaccine efficacy against infections in healthcare professionals, as well as relatively high viral loads, suggesting that infected individuals were contagious.


Medscape article – Second COVID Booster Has ‘Marginal Benefits’ in Small Study (Open access)


NEJM article – Efficacy of a Fourth Dose of Covid-19 mRNA Vaccine against Omicron (Open access)


See more from MedicalBrief archives:


Warning from WHO and EU regulator against repeat COVID boosters


Boosters up to 68% effective against hospitalisation following Omicron reinfection – CDC study


Second Pfizer booster only protects short-term against Omicron – Large Israeli study



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