The Perfect Enemy | Updated COVID booster tied to strong Omicron immune response
October 5, 2022
Read Time:4 Minute

The new bivalent (two-strain) Moderna COVID-19 vaccine booster triggered stronger neutralizing antibody responses against the highly transmissible Omicron variant at 28 days than the previously authorized booster, with no safety concerns, according to the interim results of a phase 2/3 open-label, nonrandomized study published late last week in the New England Journal of Medicine.

“These findings indicate that bivalent vaccines may be a new tool in the response to emerging variants,” the researchers wrote.

The US Centers for Disease Control and Prevention recommended Moderna’s bivalent booster for adults on Sep 1, shortly after the Food and Drug Administration approved it, in addition to Pfizer’s bivalent version, which is approved for people 12 years and older.

New version versus old

A team led by Moderna scientists evaluated immune response and safety of the updated booster against Omicron (mRNA-1273.214), its subvariants, and previous variants with that of the older Moderna booster (monovalent vaccine; mRNA-1273) against the wild-type virus in 814 participants from Feb 18 to Mar 23, 2022. The bivalent booster was designed to target both the wild-type and Omicron viral strains.  

Participants, who had received the older booster at least 3 months before, were given either a dose of the bivalent (437 patients) or monovalent (377) vaccine as a second booster. Median time between the first and second boosters was similar for both vaccine types, at about 135 days.

Average participant age was 57.3 years in the bivalent group and 57.5 years in the monovalent group, and 59.0% and 50.7% were women, respectively. In the bivalent group, 22.0% of participants were previously infected with SARS-CoV-2, as were 26.8% in the monovalent group.

Higher antibody levels against all variants

At 28 days, patients with no previous COVID-19 diagnosis had a geometric mean titer (GMT) of neutralizing antibodies against the Omicron BA.1 subvariant of 2,372.4 (95% confidence interval [CI], 2,070.6 to 2,718.2) after receipt of the bivalent booster and 1,473.5 (95% CI, 1,270.8 to 1,708.4) after the monovalent booster.

The geometric mean levels of neutralizing antibodies against the wild-type strain were 5,977.3 (95% CI, 5,321.9 to 6,713.3) among bivalent booster recipients, compared with 5,649.3 (95% CI, 5,056.8 to 6,311.2) among monovalent recipients.

The bivalent booster generated antibody geometric mean concentrations (GMCs) of 727.4 (95% CI, 632.8 to 836.1) and 492.1 (95% CI, 431.1 to 561.9) against the Omicron BA.4 and BA.5 subvariants, respectively (GMT ratio, 1.69; 95% CI, 1.51 to 1.90). The newer booster also produced greater binding antibody responses against previous strains such as Alpha, Beta, Gamma, and Delta (GMT ratios, 1.11 [95% CI, 1.03 to 1.19] to 1.24 [95% CI, 1.14 to 1.35]).

After adjustment for age-group and pre-booster antibody levels, estimated GMTs were 6,422.3 (95% CI, 5,990.1 to 6,885.7) and 5,286.6 (95% CI, 4,887.1 to 5,718.9) against the wild-type virus 28 days after bivalent and monovalent vaccination, respectively (GMT ratio, 1.22; 97.5% CI, 1.08 to 1.37).

At 28 days, estimated GMCs against Omicron were 2,479.9 (95% CI, 2,264.5 to 2,715.8) and 1,421.2 (95% CI, 1,283.0 to 1,574.4) with the bivalent and monovalent boosters, respectively (GMT ratio, 1.75; 97.5% CI, 1.49 to 2.04).

Among previously infected participants, GMTs were higher after the bivalent than the monovalent booster against both wild-type and Omicron strains (GMT ratios, 1.27 [95% CI, 1.07 to 1.51] and 1.90 [95% CI, 1.50 to 2.40], respectively). The percentage of participants who produced antibodies against the wild-type and Omicron strains was 100% in both groups. Relative to the monovalent booster, the bivalent version also triggered higher spike-binding antibody responses against all tested variants.

Previously infected participants had greater mean GMCs against the Omicron subvariants after the bivalent than after the monovalent booster (2,337.4 [95% CI, 1,825.5 to 2,992.9] vs 1,270.8 [95% CI, 987.3 to 1,635.8]), as did all participants regardless of previous infection status (940.6 [95% CI, 826.3 to 1,070.6] vs 645.4 [95% CI, 570.1 to 730.6]; GMT ratios, 1.60 [95% CI, 1.34 to 1.91] and 1.68 [95% CI, 1.52 to 1.84]).

Similar safety profiles

The safety and reactogenicity of the two boosters were comparable and, while the study didn’t evaluate vaccine effectiveness, an exploratory analysis showed that 11 participants (2.5%) in the bivalent group and 9 participants (2.4%) in the monovalent group tested positive for COVID-19.

Over median follow-ups of 43 days for the bivalent booster and 57 days for the monovalent version, rates of adverse events within 7 days of vaccination were similar, and most were mild or moderate. In both groups, the most common local reaction was pain at the injection site, while the most common systemic reactions were fatigue, headache, and muscle and joint pain.

A total of 18.5% of the bivalent group and 20.7% of the monovalent group experienced adverse events 28 days or more after the second booster. Of those, 5.7% and 5.8%, respectively, were considered vaccine-related, and none were severe.