In September, Health Canada approved the use of a first-generation bivalent booster vaccine against the SARS CoV-2 virus for use in adults aged >18 years (www.canada.ca/en/health-canada/news/2022/09/health-canada-authorizes-first-bivalent-covid-19-booster-for-adults-18-years-and-older.html).
The bivalent booster (mRNA-1273.214) includes antigen from the original CoV-2 virus strain and the Omicron BA.1 variant. SPIKEVAX Bivalent (elasomeran/imelasomeran) is administered as one 50 mcg intramuscular injection at least four months after a primary series (two injections) or a booster (i.e. as a first or second booster). A 15-minute observation period is advised post-injection.
Approval was based on safety and immunogenicity data rather than vaccine efficacy. The results are published as a preprint (Chalkias et al. medRxiv preprint, June 25, 2022; free full text at www.medrxiv.org/content/10.1101/2022.06.24.22276703v1.full.pdf). In the phase II/III P205 (Part G) study, 814 subjects were randomized to the bivalent booster or the original vaccine (mRNA-1273). All subjects had received the original vaccine as a first booster. Median interval between the third and fourth dose was 4.5 months. Omicron neutralizing antibody geometric mean titres (GMT) at day 29 were higher with the bivalent vs. original vaccine (3070 vs. 1933). Similar differences were seen in the previously uninfected subgroup (2372 vs. 1473) and in the prior infection subgroup (7676 vs. 3886).
Since the development of the bivalent vaccine, two subvariants of concern (BA.4/BA.5) have predominated. Neutralizing antibody titres against BA.4/BA.5 were more modest with the bivalent vaccine but superior to what was seen with the original vaccine (941 vs. 645).
The frequency of adverse effects with the bivalent vaccine was similar to what was seen with the original mRNA-1273 vaccine. The most frequent adverse effects were pain at the injection site (77%), fatigue (55%), headache (44%), myalgia (40%), arthralgia (31%), chills (24%) and axillary swelling or tenderness (17%). Median duration of follow-up was 43 days.
Additional studies are needed to determine vaccine efficacy and the duration of protection from a second booster injection.
It should be noted that the Canadian booster is not the same as the one that received emergency use authorization in August by the FDA. That booster (mRNA-1273.222), which the FDA is calling an updated booster, combines the original vaccine with Omicron subvariant BA.4/BA.5 spike proteins. Due to an absence of data, authorization was based on the safety results of the mRNA-1273.214 study cited above and an unpublished preclinical study, which reported little additional benefit with the updated booster compared to the mRNA-1273.214 booster even against the BA.5 subvariant (Scheaffer et al, in preparation). A human trial, Study 205 Part H, is ongoing.