Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants have caused multiple waves of COVID-19 infections globally. Booster campaigns have been set up to reduce the burden of the pandemic. This phase II/III study evaluated the safety and immunogenicity of the bivalent vaccine candidate mRNA-1273.211.
Since the primary SARS-CoV-2 virus, several SARS-CoV-2 mutations have emerged such as Beta (b.1.351), Delta (B.1.617.2) and Omicron (B.1.1.529). These mutations enhanced the transmissibility of the virus, associated with increased morbidity and mortality.
A booster dose was introduced to increase the antibodies against coronavirus variants. The initial mRNA-1273 (Moderna) vaccine encodes the spike protein of the ancestral SARS-CoV-2 (Wuhan-HU-1 isolate) and was well tolerated and demonstrated 93.2% efficacy against COVID-19 after a median follow-up of 5.3 months following a 2-dose 100 µg primary series in the phase III COVE trial.
The mRNA-1273 vaccine generated higher titers against the ancestral virus, but Beta- and Omicron-antibodies appeared to be lower. It was therefore that a bivalent booster vaccine was proposed.
This bivalent booster vaccine was produced consisting of both mRNA of ancestral SARS-CoV-2 and Beta variant spike proteins (1:1). It was hypothesized that this bivalent mRNA-1273.211 booster vaccine would enhance the immune response by increasing antibody diversity.
Participants received a 50 µg (n=300) or 100 µg (n=595) booster dose approximately 8.8 to 9.8 months after the primary mRNA-1273 dose. Results were compared to historical controls (n=584) from the COVE trial that received a mRNA-1273 (100 µg) vaccine.
The mRNA-1273.211 booster (both 50 and 100 µg) proved higher neutralizing antibody responses against the ancestral SARS-CoV-2 and the Beta variant than that after the second mRNA‑1273 dose. Antibody responses after the 50 µg mRNA-1273.211 booster dose were also higher than that after a 50 µg mRNA-1273 booster dose for the ancestral SARS-CoV-2, Beta, Omicron and Delta variants (28 days after the booster dose) and for the ancestral SARS-CoV-2, Beta and Omicron (180 days after the booster dose). Immunogenicity objectives were met.
The safety and reactogenicity profile of the mRNA-1273.211 booster (50 µg) was comparable to mRNA-1273 (50 µg). Adverse events of mRNA-1273.211 (50 µg versus 100 µg) consisted of injection site pain (85% versus 91%), fatigue (64% versus 70%), headache (51% versus 56%), and myalgia (49% and 56%).
These results indicate that bivalent booster vaccines can induce potent and durable antibody responses providing a new tool in response to emerging variants.
Following a 50 µg booster dose of mRNA-1273, antibodies against variants such as Delta and Omicron were detectable at higher titers than after the mRNA-1273 primary series.10,15 However, antibody titers, especially against antigenically divergent variants such as Omicron appear to be lower than that against the ancestral SARS-CoV-2 and wane over time after a 50 µg dose of the prototype booster. In addition, emerging vaccine effectiveness data suggest decreased long-term booster vaccine effectiveness against infection from Omicron, although protection against hospitalization and severe disease is maintained.