Moderna said it will proactively address the emerging SARS-CoV-2 variants by testing two approaches to a booster vaccine, according to a press release from the company.
Moderna is developing an emerging variant booster candidate (mRNA-1273.351) against the B.1.351 variant first identified in the Republic of South Africa. Moderna plans to move into preclinical studies and a Phase 1 study of mRNA-1273.351 in the United States to evaluate the immunological benefit of boosting with strain-specific spike proteins.
The company said it also plans to test an additional booster dose of its COVID-19 vaccine (mRNA-1273) to study the ability to further increase neutralizing titers against emerging strains beyond the existing primary vaccination series.
Moderna said it decided to evaluate two types of booster shots of its vaccine even though results from in vitro neutralization studies of sera from individuals vaccinated with Moderna COVID-19 were positive. The study showed that vaccination with Moderna’s COVID-19 vaccine produced neutralizing titers against all key emerging variants tested, including B.1.1.7, first identified in the United Kingdom, and B.1.351. The study showed no significant impact on neutralizing titers against the B.1.1.7 variant relative to prior variants. However, a six-fold reduction in neutralizing titers was observed with the B.1.351 variant relative to prior variants.
Despite this reduction, neutralizing titer levels with B.1.351 remain above levels that are expected to be protective, Moderna said, while adding that the 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.
“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,” said Stéphane Bancel, Chief Executive Officer of Moderna.
First detected in September 2020 in the United Kingdom, the SARS-CoV-2 B.1.1.7 variant has seventeen mutations in the viral genome with eight mutations located in the spike (S) protein. The B.1.351 variant, first detected in South Africa, has ten 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 (18-55 years old) 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.
