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Bivalent Moderna vaccine likely to protect against Omicron sub-variants

A bivalent Moderna vaccine was found to produce a potent neutralising antibody response against two Omicron sub-variants BA.4 and BA.5

A bivalent Moderna vaccine is able to generate a large neutralising antibody response against two of the Omicron sub-variants, BA.4 and BA.5 and therefore likely to protect against these variants.

Both the BA.4 and BA.5 sub-variants of Omicron were detected in South Africa in January and February 2022, respectively. Moreover, there have recently been concerns raised over these two sub-variants especially after a study published in the New England Journal of Medicine, found that the sub-variants, substantially escaped neutralising antibodies induced by both vaccination and infection.

The results of the study showed that among individuals who had received a third (i.e., booster) dose of BNT162b, compared with the response against the original COVID-19 isolate, the neutralising antibody titre was lower by a factor of 21 against BA.4 or BA.5. In other words, it appears highly likely that even among those who have been fully vaccinated, the BA.4 and BA.5 can lead to re-infection.

The bivalent Moderna vaccine has been studied in a phase 2 and phase 3 trial which has yet to be published. In the study, all participants who had previously received 2 or 3 doses of an approved COVID-19 vaccine were then given mRNA-1273.529, mRNA-1273.214, or mRNA-1273 as the 4th dose.

Bivalent Moderna vaccine and Omicron sub-variants

When considering the COVID booster candidate, mRNA-1273.214, only one month after administration in previously boosted participants, a 50 µg booster dose elicited potent neutralising antibody responses against the Omicron sub-variants BA.4 and BA.5 in all participants.

In fact, mRNA-1273.214 was able to increase the level of neutralising antibody titres against BA.4/BA.5 by 5.4-fold (95% CI 5.0 – 5.9) above baseline in all participants regardless of prior infection and by 6.3-fold (95% CI 5.7 – 6.9) in the subset of seronegative participants.

These results follow on from previous data from early June 2022, in which Moderna found that a booster dose with mRNA-1273.214 increased neutralising geometric mean titres (GMT) against the Omicron variant by approximately 8-fold above baseline levels.

Moreover, a 50 μg booster dose of mRNA-1273.214 was well-tolerated in the 437 study participants and both the safety and reactogenicity profile of mRNA-1273.214 was similar to that of mRNA-1273 when these vaccines were administered as a second booster dose.

Based on these preliminary findings, Moderna is now working hard to complete all the necessary regulatory submissions in the coming weeks requesting to update the composition of the booster vaccine to mRNA-1273.214.

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