The U.S. Food and Drug Administration will meet later this month to consider approval of two bivalent COVID-19 booster vaccines that are reportedly effective against the Omicron variant (B.1.1.529). Both boosters were developed by Moderna and are variations of the company’s original mRNA-1273 vaccine.
The first of the Moderna boosters, mRNA-1273.211, contains equal mRNA amounts of ancestral SARS-CoV-2 (Wuhan isolate) and Beta variant spike proteins. The phase II/III trial enrolled 896 adult participants (mean age 50.7 years) from the COVE trial, in which all subjects received two doses of the Moderna vaccine (Baden et al. N Engl J Med 2021;384:403-416). The bivalent booster (50 or 100 µg) was administered at least 6 months (mean 264-294 days) after the original two-shot regimen. A separate phase II study of the original mRNA-1273 booster (n=171) served as an external comparator.
The trial results are available as a preprint only (Chalkias et al. Research Square, April 15, 2022; free full text at file:///D:/May%202022/Moderna_bivalent%20vaccine.pdf). The geometric mean neutralizing antibody titre (GMT) was two-fold higher against the Omicron variant with the mRNA-1273.211 bivalent booster versus the original mRNA-1273 booster at 28 days (GMT 1380.8 vs. 630.5) and 180 days post-injection (GMT 312.9 vs. 145.6). The most common systemic adverse reactions with the bivalent booster were fatigue (64%), headache (51%) and myalgia (49%).
The second Moderna booster, mRNA-1273.214, combines the standard vaccine with Omicron-specific antigens and is the lead candidate for use as the new booster injection this fall. The data have not been published but have been presented at an investor meeting. All subjects had previously received the two-dose regimen plus a booster. The phase II/III study (N=814) evaluated the novel bivalent vaccine as a fourth injection (second booster).
According to the interim results, the vaccine outperformed the initial vaccine in neutralizing antibody response against the Omicron variant. At day 29, GMT was 1.78-fold higher against Omicron with the bivalent booster compared to the original vaccine (3232.52 vs. 1815.14). The neutralizing antibody responses to Omicron were also superior in subjects previously infected with COVID-19 (7676 vs. 3886) and in seronegative individuals (2372 vs. 1473).
A second trial of the mRNA-1273-14 booster following various initial vaccine regimens is ongoing in the U.K.
A U.K. study recently reported that a two-dose regimen of the Pfizer or AstraZeneca vaccines had limited effectiveness against the Omicron variant (Andrews et al. N Engl J Med 2022;386:1532-1546). Effectiveness of the Pfizer vaccine against Omicron was 65.5% at 2-4 weeks but declined to 8.8% at >25 weeks. The AstraZeneca vaccine had no effect on Omicron after week 20.
To listen to the interim analysis presented to Moderna investors, click here: https://investors.modernatx.com/events-and-presentations/events/default.aspx.