Moderna’s COVID-19 Vaccine Effective Against New Variants

Moderna’s COVID-19 Vaccine Effective Against New Variants

As new variants of SARS-CoV-2 are being identified, there has been some concern that current vaccines may not perform against them. To address this, Moderna evaluated its mRNA-1273 COVID-19 vaccine against variants including the B.1.1.7 and B.1.351 strains.

COVID-19 vaccine maker Moderna announced this week that results from a study show that the shot is effective against some of the new circulating variants of SARS-CoV-2.

The company used in vitro neutralization antibody studies to evaluate the activity of Moderna’s vaccine-generated antibodies from human sera against several variants of the novel coronavirus, including the B.1.1.7 strain that was first found in the UK and B.1.351 that was first identified in South Africa.

In a news release from Moderna, the company reported that the administration of its COVID-19 vaccine induced antibody titers against both variants. While there was no significant impact on neutralizing titers from the convalescent sera against B.1.1.7, a six-fold reduction in neutralizing titers was observed for the B.1.351 variant relative to previous variants. Despite the reduction, neutralizing titer levels for B.1.351 remain above levels that are expected to be protective, the company said.

Results of the study were published on the bioRxiv preprint server for biology and the manuscript will be submitted for peer-reviewed publication shortly.

Moderna’s mRNA-based COVID-19 vaccine (mRNA-1273) vaccine was found to be 94.5 percent effective in preventing infection and 100 percent efficacy at preventing severe disease in Phase III studies. The vaccine has been given emergency use authorization (EUA) in the US and is approved by Health Canada.

Related: Moderna’s COVID-19 Vaccine Candidate Shows Almost 95 Percent Effectiveness

The study was conducted in collaboration with the Vaccine Research Center (VRC) at the National Institute of Allergy and Infectious Diseases (NIAID), which is part of the National Institutes of Health (NIH).

“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 in the news release.

The in vitro study evaluated the ability of mRNA-1273-generated antibodies to neutralize the new SARS-CoV-2 variants. For this, sera were used from eight participants (aged 18-55 years) from the Phase I clinical trial of Moderna’s vaccine study who received two 100 µg doses of mRNA-1273. Sera from non-human primates (NHPs) immunized with two doses of 30 µg or 100 µg of mRNA-1273 were also assessed for antibody titers.

Two independent pseudovirus neutralization (PsVN) assays were employed: one lentiviral-based and the other using a recombinant vesicular stomatitis virus (VSV), both bearing variants of the spike protein including those found in B.1.1.7 and B.1.351.

Neutralization of the B.1.1.7 variant with either human or NHP sera was high and comparable to that of previous variants. There was no significant effect on neutralization against the full set of mutations found in the B.1.1.7 variant or from specific mutations. This despite the fact that the mutations have been reported to reduce neutralization from convalescent sera and increase infectiousness.

For the B.1.351 variant, a 6.4-fold lower neutralization was observed against the full host of mutations in the variant. These lower titers may suggest a potential risk of early waning of immunity to new variants arising from the B.1.351 lineage.

Although Moderna expects that its two-100 µg dose vaccine regimen will  protect against the new emergent strains identified thus far, the company announced its proactive clinical strategy to address the pandemic as the virus continues to evolve.

As part of its approach going forward, the company will assess the effects of an additional booster dose of the vaccine in aims to potentially increase neutralizing antibody titers — beyond the titers achieved with the two-dose regimen — against all currently circulating strains.

The company is also advancing development of avariant booster candidate (mRNA-1273.351) specifically against the B.1.351 variant. mRNA-1273.351 will be evaluated in preclinical studies and a Phase I study in the US to evaluate the immunological benefit of boosting with strain-specific spike proteins said Moderna. It is expected that an additional dose of either mRNA-1273 or mRNA-1273.351 should be able to further increase neutralizing titers of the parent vaccine, as well as in combination with some of the other leading vaccine candidates.

“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,” Bancel said.

The two variants studied have mutations in the spike protein of SARS-CoV-2, with 17 mutations in B.1.1.7 of which eight are located in the spike protein, and ten identified in the spike protein in B.1.351. Both contain the N501Y mutation — which is a mutation found in other lineages as well — while B.1.3351 also has more “concerning” E484K and K417N mutations at key sites in the receptor binding domain (RBD) of the spike protein.

Both variants are associated with increased transmission and higher viral loads upon infection, and have spread rapidly around the world. While it is normal for viruses to acquire mutations, the lower the number of hosts that the virus takes up residence in, the less chances it has to mutate. Therefore, controlling transmission remains a priority despite having COVID-19 vaccines in our arsenal now.