Studies examine durability of mRNA vaccine against SARS‑CoV‑2 omicron sublineages

A study published in The New England Journal of Medicine assessed the effectiveness and durability of the BNT162b2 (Pfizer-BioNTech) vaccine against severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) omicron BA.1 or BA.2 and against BA.4 or BA.5 subvariants among individuals who received two and three doses of the vaccine.

During the period from November 15, 2021 to June 24, 2022, a total of 32,883 patients who had been hospitalised for medical treatment underwent PCR testing for SARS-CoV-2, a period that spanned the BA.1–BA.2 and BA.4–BA.5 omicron waves. Of these patients, 5,909 (18.0%) were found to be positive for SARS-CoV-2. Vaccination status was analysed according to the time that had elapsed since the administration of the most recent dose of vaccine.

“Among the patients who had received two doses of vaccine, waning of effectiveness against hospitalisation was evident as early as 3 to 4 months after vaccination during both periods when the omicron sublineages were dominant,” reported Shirley Collie, Discovery Health, Sandton, South Africa, and colleagues.

Specifically, the study found that the 2-dose vaccine effectiveness was 56.3% (95% confidence interval [CI], 51.6 to 60.5) during the BA.1–BA.2 wave and 47.4% (95% CI, 19.9 to 65.5) during the BA.4–BA.5 wave. Although boosting with a third dose maintained vaccine effectiveness against severe disease caused by all four sublineages at 1 to 2 months, with vaccine effectiveness of 66.4% (95% CI, 53.7–75.6) and 68.8% (95% CI, 59.5–76.0) during the BA.1–BA.2 wave and BA.4–BA.5 wave, respectively, the vaccine effectiveness had decreased by 3 to 4 months to an effectiveness of 50.0% (95% CI, 4.4 to 73.9) during the BA.1–BA.2 wave and 46.8% (95% CI, 35.3 to 56.2) during the BA.4–BA.5 wave.

“Thus, after either two doses or three doses of the BNT162b2 vaccine, we found rapid waning of vaccine effectiveness against the current sublineages of the omicron variant with respect to protection against hospitalisation,” the authors noted.

“Our data indicate that boosting maintains vaccine effectiveness against severe disease caused by the current omicron sublineages, although the evidence of rapid waning of durability indicates the need for regular boosting as early as 4 months after the last dose or the need for vaccines to incorporate variants of concern to maintain protection,” the authors added. 

Meanwhile, another study, also published in The New England Journal of Medicine, assessed the durability of booster mRNA vaccine against SARS‑CoV‑2 omicron BA.2.12.1, BA.4, and BA.5 subvariants.

In the study, researchers led by Panke Qu, Ohio State University, Columbus, Ohio, examined neutralising-antibody titres against major SARS-CoV-2 variants in a longitudinal cohort of health care workers who had received homologous vaccine and booster doses of mRNA-1273 (Moderna; n = 24) or BNT162b2 vaccine (n = 22). Participant samples were classified into three groups according to the timing of booster-dose administration: 1 to 3 months, 4 to 6 months, and 7 to 9 months before the sample was obtained. Over the course of the study, 14 participants had a breakthrough infection, with 9 cases occurring during the omicron waves.

Overall, the researchers observed that booster durability waned more substantially in participants who did not have breakthrough infection than in those who had breakthrough infection, with neutralising-antibody titres, presented as 50% neutralisation titres (NT50), against all variants at 1 to 3 months after the booster dose being approximately 1.7 times (95% CI, 1.4 to 2.2) as high as those observed at 7 to 9 months after the booster dose. 

Linear modeling showed a mean 30-day rate of decay in neutralising-antibody titres of 17.53% (95% CI, 11.87 to 22.79) against virus with the D614G mutation, 19.50% (95% CI, 9.82 to 28.10) against the omicron BA.1 subvariant, 18.44% (95% CI, 9.24 to 26.68) against BA.2.12.1, and 19.55% (95% CI, 10.54 to 27.66) against BA.4/5. Participants with previous SARS-CoV-2 infection, including infection with the omicron variant, had a somewhat less steep rate of decay in neutralizing-antibody titres with 30-day rates of 17.07% (95% CI, 2.70 to 29.29) against virus with the D614G mutation, 14.22% (95% CI, −6.87 to 31.13) against the BA.1 subvariant, 9.97% (95% CI, −11.95 to 27.64) against BA.2.12.1, and 12.12% (95% CI, −7.14 to 27.94) against BA.4/5. At all time points tested, all the omicron subvariants, especially BA.4/5, had lower neutralising-antibody titres than virus with the D614G mutation.

Further, two participants received a second booster dose of mRNA vaccine. After a substantial decrease in neutralising-antibody titers was observed approximately 4 months after receipt of the initial booster dose in these participants, the administration of a second booster dose led to recovered neutralising-antibody titres.

“The decrease in booster durability appeared to be slower than the decrease that was previously reported for two doses of mRNA vaccine alone. Although the rate of booster neutralising-antibody decay was similar among variants, the omicron subvariants, especially BA.4/5, had substantial neutralisation resistance. Our observed trends are consistent with the waning of vaccine protection and natural immunity, and our data suggest that both SARS-CoV-2 variant evolution and waning neutralising-antibody titers reduce booster-induced immune protection,” the authors noted, adding that “our anecdotal experience in two participants indicates that a fourth dose of vaccine may be effective.”

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