Moderna said Monday that it is evaluating strategies to combat emerging strains of SARS-CoV-2, including testing an additional booster dose of its COVID-19 vaccine mRNA-1273. The company also plans to investigate a booster candidate, dubbed mRNA-1273.351, against the B.1.351/501Y.V2 variant first identified in South Africa that has already shown an ability to evade antibodies present in some coronavirus treatments.
CEO Stéphane Bancel said the company was preparing for a "worst-case scenario," despite having "zero concerns" about the efficacy of mRNA-1273 in the coming months. "What is unknowable right now is what will happen in six months, 12 months, especially to the elderly because…they have a weaker immune system," Bancel remarked. Shares in the company were up as much as 12% on the news.
According to Moderna, while the current two-dose regimen of mRNA-1273 at the 100-mcg dose is expected to be protective against emerging strains detected to date, it is looking at other strategies "out of an abundance of caution." The company said it is advancing mRNA-1273.351 into preclinical testing, as well as a Phase I study in the US to evaluate the benefit of boosting with strain-specific spike proteins. However, regardless of whether it is mRNA-1273 or mRNA-1273.351, the company believes its mRNA-based booster vaccine "will be able to further boost neutralising titers in combination with all of the leading vaccine candidates."
The B.1.1.7 variant of SARS-CoV-2 first identified in the UK has 17 mutations in the viral genome, with eight located in the spike protein, while the B.1.351 strain has 10 spike mutations. Moderna said both have been associated with increased transmission and higher viral burden after infection. The company on Monday reported findings from an in-vitro study assessing the ability of mRNA-1273 to elicit neutralising antibodies against these new variants. Researchers used sera from eight Phase I study participants aged 18 to 55 years who received two 100-mcg doses of mRNA-1273, and sera from non-human primates immunised with two doses of 30 mcg or 100 mcg.
Moderna said findings published on the preprint server bioRxiv showed "no significant impact" on neutralisation observed from either the full set of mutations in the B.1.1.7 variant or from "specific key mutations of concern." However, for B.1.351, neutralising antibody titres were approximately six-fold lower relative to prior variants. While the company believes these levels are still high enough to offer protection, they "may suggest a potential risk of earlier waning of immunity" to B.1.351. "We expect that whatever immunity you get over time will wane, the question is will it wane faster if you have lower levels to begin with," commented chief medical officer Tal Zaks.
Zaks suggested the mRNA-1273.351 vaccine could be used if needed as a booster shot one year after people get the original vaccine, based either on their antibody levels or by observing the population of vaccinated individuals to see if they begin falling ill from the new variant. Zaks said "we don't yet have data on the Brazilian variant," dubbed P.1/501Y.V3, but he thinks "it should be close to the South African one. That's the one with the most overlap." Zaks noted that it took Moderna 42 days to produce the original vaccine, and the company could make a new one "hopefully a little faster this time, but not much." Meanwhile, talks with regulators about what would be required to bring a new version of the vaccine are just getting under way.
Commenting on the news, Loncar Investments CEO Brad Loncar tweeted that "the idea that Moderna is able to start developing a booster shot specifically tailored to the South African variant so quickly illustrates the versatility and speed of the mRNA platform. It's going to be hard for anything to compete with that." Results of the in-vitro study for Moderna's vaccine, which will be submitted for peer-reviewed publication, follow recent laboratory data indicating that Pfizer and BioNTech's similar mRNA-based candidate BNT162b2 is likely capable of neutralising the B.1.1.7 strain, although the companies have not provided data regarding potential efficacy against B.1.351.
Moderna's vaccine has been authorised in the US, the UK, Switzerland, the EU, Canada and Israel based on Phase III data showing an efficacy rate of 94.1% at reducing the number of symptomatic COVID-19 cases among people who had no sign of previous infection.
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