mRNA-1273.211 targets mutations found in the Beta variant, several of which have been persistent in more recent variants of concern including Omicron.
Superiority against ancestral, Beta, Delta and Omicron variants
Moderna says the 50 µg booster dose of mRNA-1273.211 meets its objectives for a bivalent booster candidate: such as superiority immunogenicity criteria against variants of concern when compared to the mRNA-1273 booster dose (50 µg).
A booster dose of mRNA-1273.211 demonstrated superiority against the ancestral SARS-CoV-2 and the Beta, Delta and Omicron variants one month after the booster dose and superiority against the ancestral SARS-CoV-2, Beta and Omicron six months compared to the booster dose of mRNA-1273.
There was a 2.20-fold (95% CI: 1.74, 2.79) and 2.15-fold (95% CI: 1.66, 2.78) increase in the neutralizing antibody titers against Omicron with the mRNA-1273.211 booster dose compared to the mRNA-1273 booster dose at one month and six months, respectively.
The mRNA-1273.211 booster candidate was generally well tolerated in 300 study participants who received the 50 µg dose and 595 participants who received the 100 µg dose of mRNA-1273.211 (895 participants in total).The 50 µg booster dose of mRNA-1273.211 had a similar incidence of solicited adverse reactions and unsolicited adverse events with the authorized mRNA-1273 booster (50 µg).
Moderna's primary focus has been on the bivalent booster approach to maintain high neutralizing antibody titers while improving breadth of immunity to variants.
Multiple bivalent booster candidates have been evaluated to date, which include mRNA-1273.211 (9 spike protein mutations, based on the Beta variant), and mRNA-1273.214 (32 spike protein mutations, based on the Omicron variant).
mRNA-1273.211 includes four mutations and mRNA-1273.214 includes 32 mutations present in the Omicron variant of concern.
Meanwhile, the company is also evaluating an updated bivalent booster incorporating more Omicron-specific mutations (mRNA-1273.214) in a Phase 2/3 clinical study, with initial data on this candidate (expected in Q2) informing the fall selection for the Northern Hemisphere booster.
Stéphane Bancel, CEO, Moderna, says the results validate the company’s bivalent strategy, which is started pursuing in February 2021.
“The results indicate that mRNA-1273.211 at the 50 µg dose level induced higher antibody responses than the 50 µg mRNA-1273 booster, even when additional variants of concern were not included in the booster vaccine.
“Our latest bivalent booster candidate, mRNA-1273.214, which combines the currently authorized Moderna COVID-19 booster with our Omicron-specific booster candidate, remains our lead candidate for the fall 2022 Northern Hemisphere booster. We look forward to sharing initial data on mRNA-1273.214 later in the second quarter. We believe that a bivalent booster vaccine, if authorized, would create a new tool as we continue to respond to emerging variants.”