Bivalent beta-containing mRNA-1273.211 booster vaccine generates higher antibody titers than mRNA-1273 booster

May 2022 Covid-19 Dominique Vrouwenvelder

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.

Bivalent booster

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.


Chalkias S, Eder F, Essink F, et al. Safety, immunogenicity and antibody persistence of a bivalent beta-containing booster vaccine. ResearchSquare. Preprint. 15 Apr, 2022. Accessed 27 May, 2022.