While most developers believe their vaccines will be effective against the strain originating in the UK, effectiveness against the South African variant has been in question. The results from Moderna’s study suggest that its vaccine will be less effective against the South African variant than others – but still effective enough to provide protection.
“The study showed no significant impact on neutralizing titers against the B.1.1.7 variant [originating in the UK] relative to prior variants,” reports Moderna.
“A six-fold reduction in neutralizing titers was observed with the B.1.351 variant [originating in South Africa] relative to prior variants. Despite this reduction, neutralizing titer levels with B.1.351 remain above levels that are expected to be protective.”
However, given this reduced efficacy, Moderna is also working on a new booster shot designed specifically against B.1.351: which could be used in combination with any COVID-19 vaccine.
Effectiveness against B.1.351
The study tested the sera from individuals vaccinated with Moderna COVID-19 vaccine against a variety of emerging strains of SARS-CoV-2 – including those originating in South Africa and the UK - finding it produced neutralizing titers against all strains tested.
The South African variant has been causing concern given that it has 10 mutations in the spike protein (as opposed to eight with the UK variant) and it is the spike protein that most vaccines target. (Both strains have spread at a rapid rate and are associated with increased transmission and higher viral burden after infection).
While the results of this study are positive, Moderna warns that the reduced efficacy of the vaccine against the South African variant could be an early warning sign that vaccine protection may not last as long as with other variants.
“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.
“For the B.1.1.7 variant [UK], 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 [South Africa], 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 we expect 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.”
The study was conducted in collaboration with the Vaccine Research Center (VRC) at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH). The manuscript has been submitted as a preprint to bioRxiv and will be submitted for peer-reviewed publication.
3 dose vaccine and SA booster shot: Moderna launches clincial strategy to address pandemic developments
Moderna will test an additional booster dose of its existing COVID-19 Vaccine (mRNA-1273) to study the ability to further increase neutralizing titers against emerging strains beyond the existing primary vaccination series. It has not revealed details, however, of how far after the existing two-dose (administered 28 days apart) this booster dose might be administered.
Secondly, it is advancing an emerging variant booster candidate (called mRNA-1273.351) against the B.1.351 [South Africa] variant. 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.
It expects that, in either case, a mRNA-based booster shot will be able to enhance neutralizing titers - even when used in combination with any of the other leading vaccines and 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.”