Regev-Yochay et al. in Israel: "Efficacy of a Fourth Dose of Covid-19 mRNA Vaccine against Omicron"

A quick summary:

 Efficacy of a Fourth Dose of Covid-19 mRNA Vaccine against Omicron

Regev-Yochay et al. in Israel looked at (publication date March 16th 2022) the immunogenicity and safety of a fourth dose (4th) of either BNT162b2 (Pfizer–BioNTech) or mRNA-1273 (Moderna) administered 4 months after the third dose in a series of three BNT162b2 doses). This was an open-label, nonrandomized clinical study assessing the 4th dose in terms of need beyond the 3rd dose. Among the ‘1050 eligible health care workers enrolled in the Sheba HCW COVID-19 Cohort, 154 received the fourth dose of BNT162b2 and, 1 week later, 120 received mRNA-1273. For each participant, two age-matched controls were selected from the remaining eligible participants’.

Researchers further reported that ‘overall, 25.0% of the participants in the control group were infected with the omicron variant, as compared with 18.3% of the participants in the BNT162b2 group and 20.7% of those in the mRNA-1273 group. Vaccine efficacy against any SARS-CoV-2 infection was 30% (95% confidence interval [CI], −9 to 55) for BNT162b2 and 11% (95% CI, −43 to 44) for mRNA-1273…most of the infected participants were potentially infectious, with relatively high viral loads (nucleocapsid gene cycle threshold, ≤25)’. Results suggest that maximal immunogenicity of mRNA vaccines is achieved after three doses. More specifically, researchers ‘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. Thus, a fourth vaccination of healthy young health care workers may have only marginal benefits’. 

Limitations included the nonrandomized design and one-week difference between enrollment, as well as the limited adherence to weekly SARS-CoV-2 testing. Additionally, researchers were unable to sequence the infecting virus and were not definitive that all cases were due to the omicron variant (though during the study, ‘omicron accounted for 100% of the isolates that were typed’). Moreover, the study group was not large enough to allow for accurate assessment of vaccine efficacy.