In the press release, Moderna indicated that the recently reported Omicron variant includes mutations noticed in the Delta variant that are believed to boost transmissibility and mutations seen in the Beta and Delta variants that are believed to promote immune escape. The combination of mutations represents a substantial potential risk to accelerate the waning of natural and vaccine-induced immunity.
A booster dose of an authorized vaccine represents the only currently available strategy for boosting waning immunity. The Moderna COVID-19 vaccine (mRNA-1273) is authorized as a booster for many populations at the 50-µg dose level. Moderna is working rapidly to test the ability of the current vaccine dose to neutralize the omicron variant, and data is expected in the coming weeks.
The manufacturer also indicated that since early 2021, Moderna has advanced a comprehensive strategy to foresee new variants of concern, and this strategy includes three levels of response should the currently authorized 50-µg booster dose of mRNA-1273 prove insufficient to boost waning immunity against the Omicron variant.
First, Moderna has already tested a higher dose booster of mRNA-1273 (100 µg) in healthy adults and has completed dosing of 306 participants in a safety and immunogenicity study of this high-dose (100-µg) booster. The 100-µg dose of mRNA-1273 has also recently been studied by the National Institutes of Health (NIH) in the United States and has largely resulted in the highest neutralizing titers against prior SARS-CoV-2 strains. Moderna is working to swiftly test sera from its high-dose booster recipients in neutralizing assays to determine if the 100-µg dose provides superior neutralizing protection against Omicron.
Second, Moderna is already studying two multivalent booster candidates in the clinic that were designed to anticipate mutations such as those that have emerged in the Omicron variant. The first candidate (mRNA-1273.211) includes several mutations present in the Omicron variant that were also present in the Beta variant of concern. Moderna has completed dosing in a potentially pivotal safety and immunogenicity study of mRNA-1273.211 at the 50-µg (N = 300) and 100-µg (N = 584) dose levels.
A second multivalent candidate (mRNA-1273.213) includes many of the mutations present in the Omicron variant that were also present in the Beta and Delta variants. Moderna has finished dosing at the 100-µg (N = 584) dose level and also plans to explore the 50-µg dose level in around 584 participants. Moderna will swiftly expand testing of sera from completed and ongoing multivalent booster studies to ascertain if these multivalent candidates are able to provide superior neutralizing protection against Omicron.
Third, Moderna will quickly advance an Omicron-specific booster candidate (mRNA-1273.529). This candidate is part of the company's strategy to advance variant-specific candidates for a subset of variants of significant concern. During 2021, this has already included Beta- and Delta-specific boosters, and Moderna has continually demonstrated the ability to advance new candidates to clinical testing in 60 to 90 days.
In the press release, Stéphane Bancel, chief executive officer of Moderna, stated, "From the beginning, we have said that as we seek to defeat the pandemic, it is imperative that we are proactive as the virus evolves. The mutations in the Omicron variant are concerning and for several days, we have been moving as fast as possible to execute our strategy to address this variant. We have three lines of defense that we are advancing in parallel: we have already evaluated a higher dose booster of mRNA-1273 (100 µg), second, we are already studying two multi-valent booster candidates in the clinic that were designed to anticipate mutations such as those that have emerged in the Omicron variant and data is expected in the coming weeks, and third, we are rapidly advancing a Omicron-specific booster candidate (mRNA-1273.529)."
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