Moderna’s BA.4/BA.5 Targeting Bivalent Boosters Superior to Booster Dose of Standard mRNA Vaccine


Compared to the original mRNA-1273 booster dose, the bivalent booster mRNA -1273.222 was superior against Omicron variants.

In a phase 2/3 clinical trial (NCT04927065) of Moderna’s BA.4/BA.5 targeting bivalent boosters, both mRNA-1273.222 and mRNA-1273.214 produced significantly higher neutralizing antibody titers than a booster dose of mRNA-1273 (Spikevax), according to a company press release.1

These results build upon previous data published in the New England Journal of Medicine2 confirming the superiority of Moderna’s BA.1 bivalent vaccine, mRNA-1273.214, and its ability to neutralize titers against multiple Omicron variants.

In an analysis, both mRNA-1273.222 and mRNA-1273.214 displayed neutralizing titers against BQ.1.1.

Participants of the study received mRNA-1273.222 and mRNA-1273 about 9.5 months and 4.5 months after their prior vaccination, respectively. The pre-booster BA.4/BA.5 titers between mRNA1273.222 and mRNA-1273 were similar, with the mean geometric mean titer ratios at 5.11 and 6.29.

All participants’ geometric mean titer against Omicron BA.4/BA.5 saw a 15.1-fold increase from their pre-booster levels. In patients without prior infection, the geometric mean titer was 2325, a 26.4-fold increase from pre-booster levels, while those with prior infection had a geometric mean titer of 6965, a 9.8-fold increase.

Results were consistent between the age groups of 65 years and older and ages 18 to 65.

No new safety concerns were identified at 1- or 3-month follow-ups. Adverse reactions that occurred as a result of mRNA-1273.222 and mRNA-1273.214 were similar or lower than that of a second or third dose of the original vaccine.

"We are pleased to see that both of our bivalent booster vaccine candidates offer superior protection against Omicron BA.4/BA.5 variants compared to our original booster, which is encouraging given COVID-19 remains a leading cause of hospitalization and death globally. In addition, the superior response against Omicron persisted for at least three months after the mRNA-1273.214 booster," said Moderna’s chief executive officer, Stéphane Bancel.


  1. Moderna’s BA.4/BA.5 targeting bivalent booster, mRNA-1273.222, meets primary endpoint of superiority against omicron variants compared to booster dose of mRNA-1273 in phase 2/3 clinical trial. News release. Moderna. November 14, 2022. Accessed November 14, 2022.
  2. Chalkias S, Harper C, Vrbicky K, et al. A bivalent omicron-containing booster vaccine against COVID-19. N Engl J Med. 2022;387(14):1279-1291. Doi:10.1056/NEJMoa2208343
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