Booster doses with Moderna's COVID-19 vaccines show promise against variants

Moderna released initial data showing that a third dose of either its existing COVID-19 vaccine mRNA-1273, or a new modified variant-specific candidate, boosted neutralising titres against two mutated SARS-CoV-2 strains in previously immunised people. "We are encouraged by these new data, which reinforce our confidence that our booster strategy should be protective against these newly detected variants," commented CEO Stéphane Bancel.

The Phase II study is evaluating three strategies for boosting neutralising titres in people previously inoculated with its two-dose mRNA-1273 vaccine. One strategy involves giving a 50-mcg booster of the same vaccine. The others call for boosting with mRNA-1273.351, a candidate based on the B.1.351 variant, or with mRNA-1273.211, an experimental multivalent vaccine that combines a 50-50 mix of mRNA-1273 plus mRNA-1273.351 in a single dose.

Prior to boosting, Moderna said participants in the study were tested for antibody persistence about six to eight months after their primary vaccination series. While titres versus wild-type SARS-CoV-2 remained high and were detectable in 37 of 40 participants, they were "much lower" against the B.1.351 and P.1 variants of concern, with roughly half the participants having titres below the assay's limit of quantification threshold.

Less waning of immunity with B.1.351-specific vaccine

The latest findings are derived from data at two weeks following a booster with either mRNA-1273 or mRNA-1273.351. Moderna said both increased neutralising titres against the B.1.351 and P.1 variants, with geometric mean titre (GMT) levels at or above peak titres reported against the original strain following primary vaccination. "The strong and rapid boost in titres to levels above primary vaccination also clearly demonstrates the ability of mRNA-1273 to induce immune memory," Bancel added.

The results also suggest mRNA-1273.351 may be more effective at neutralising B.1.351 than Moderna's currently authorised vaccine, based on GMT values of 1400 and 864 for the two shots, respectively, measured two weeks after the booster. Moreover, a previously observed decrease in neutralising titres between the wild-type and B.1.351 assays also improved with mRNA-1273.351, from a 7.7-fold difference prior to boosting, to a 2.6-fold difference 15 days after, something Moderna says points to a "more balanced immune response against the tested variants."

Moderna said safety profiles following booster injections of mRNA-1273 at 50 mcg or mRNA-1273.351 were "generally comparable" to those seen after the second dose of its existing vaccine. The frequency of any grade 3 solicited local or systemic adverse events was 15% after the third dose of mRNA-1273 and 10.5% after the booster dose of mRNA-1273.351, while there were no grade 4-level side effects.

Multivalent candidate data forthcoming

The company is also looking at additional samples collected at later timepoints, as well as a lower dose of mRNA-1273.351, and expects data to be available soon. Meanwhile, evaluation of the multivalent mRNA-1273.211 booster candidate is ongoing, with results expected shortly there as well. Last month, Moderna reported non-peer-reviewed preclinical findings showing that mRNA-1273.211 induced the "broadest level of immunity," while a boost with mRNA-1273.351 at six months "closed the neutralising titre gap" for variants of concern, resulting in comparable titre levels between the ancestral SARS-CoV-2 strain and B.1.351.

Bancel reiterated that Moderna's "mRNA platform allows for rapid design of vaccine candidates that incorporate key virus mutations, potentially allowing for faster development of future alternative variant-matched vaccines should they be needed." On Thursday, Moderna reported that sales of mRNA-1273 reached $1.7 billion in the first quarter, reflecting the delivery of 102 million doses, leading the company to post its first-ever profit.

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