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Moderna COVID-19 Vaccine Neutralizes Emerging UK and South African SARS-CoV-2 Strains

By HospiMedica International staff writers
Posted on 26 Jan 2021
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Results from in vitro neutralization studies of sera from individuals vaccinated with Moderna, Inc.’s (Cambridge, MA, USA) mRNA-1273 COVID-19 vaccine have shown neutralizing activity against the emerging strains of SARS-CoV-2 that were first identified in the UK and South Africa.

The UK SARS-CoV-2 B.1.1.7 variant has 17 mutations in the viral genome with eight mutations located in the spike (S) protein. The B.1.351 South African variant has 10 mutations located in the spike (S) protein. Both variants have spread at a rapid rate and are associated with increased transmission and a higher viral burden after infection. The in vitro study assessed the ability of mRNA-1273 to elicit potently neutralizing antibodies against the new SARS-CoV-2 variants, using sera from eight Phase 1 clinical trial participants (aged 18-55 years) who received two 100 µg doses of mRNA-1273, and separately using sera from non-human primates (NHPs) immunized with two doses of 30 µg or 100 µg of mRNA-1273.

Vaccination with the Moderna COVID-19 vaccine produced neutralizing titers against all the key emerging SARS-CoV-2 variants tested, including B.1.1.7 and B.1.351. For the B.1.1.7 variant, neutralizing antibody titers remained high and were generally consistent with neutralizing titers relative to prior variants. No significant impact on neutralization was observed from either the full set of mutations found in the B.1.1.7 variant or from specific key mutations of concern. Although these mutations have been reported to lessen neutralization from convalescent sera and to increase infectivity, sera from the Phase 1 participants and NHPs immunized with mRNA-1273 were able to neutralize the B.1.1.7 variant to the same level as prior variants.

For the B.1.351 variant, vaccination with the Moderna COVID-19 vaccine produces neutralizing antibody titers that remain above the neutralizing titers that were shown to protect NHPs against wildtype viral challenge. While the company expects these levels of neutralizing antibodies to be protective, pseudovirus neutralizing antibody titers were approximately 6-fold lower relative to prior variants. These lower titers may suggest a potential risk of earlier waning of immunity to the new B.1.351 strains.

Although the two-dose regimen of the Moderna COVID-19 vaccine at the 100 µg dose is expected to be protective against emerging strains detected to date, the company will test an additional booster dose of its mRNA-1273 vaccine in order to study its ability to further increase neutralizing titers against emerging strains beyond the existing primary vaccination series. Moderna is also advancing an emerging variant booster candidate (mRNA-1273.351) against the B.1.351 variant. Additionally, the company is advancing mRNA-1273.351 into preclinical studies and a Phase 1 study in the US to evaluate the immunological benefit of boosting with strain-specific spike proteins. Moderna expects its mRNA-based booster vaccine (whether mRNA-1273 or mRNA-1273.351) to further boost neutralizing titers in combination with all of the leading vaccine candidates.

“As we seek to defeat the COVID-19 virus, which has created a worldwide pandemic, we believe it is imperative to be proactive as the virus evolves. We are encouraged by these new data, which reinforce our confidence that the Moderna COVID-19 vaccine should be protective against these newly detected variants,” said Stéphane Bancel, Chief Executive Officer of Moderna. “Out of an abundance of caution and leveraging the flexibility of our mRNA platform, we are advancing an emerging variant booster candidate against the variant first identified in the Republic of South Africa into the clinic to determine if it will be more effective to boost titers against this and potentially future variants.”

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