Moderna’s booster vaccine effective against South Africa and Brazil variants of concern

Moderna’s mRNA booster vaccine is effective against variants of concern that emerged in South Africa and Brazil. Initial data from a Phase 2 study has shown that a single 50 µg dose of mRNA-1273 or a customized booster (called mRNA-1273.351) given to previously vaccinated individuals increased neutralizing antibody titer responses against SARS-CoV-2 and two variants of concern, B.1.351 (first identified in South Africa) and P.1 (first identified in Brazil).  The mRNA-1273.351 booster dose produced higher neutralizing antibody titers against B.1.351 variant compared to a booster dose of mRNA-1273. 

The trial participants were tested for pseudovirus neutralization (PsVN) titers prior to boosting approximately 6 to 8 months after their primary vaccination series. Although titers versus the wild-type SARS-CoV-2 virus remained high, with 37 of 40 participants having detectable titers, titers against the variants of concern (B.1.351 and P.1) were much lower, with about half of participants having titers below the assay limit of quantification prior to boosting.

• Two weeks after receiving either mRNA-1273 or mRNA-1273.351, PsVN titers were boosted in all participants and all variants tested.
• Following boost, geometric mean titers (GMT) against the wild-type, B.1.351, and P.1 variants increased to levels similar to or higher than the previously reported peak titers against the ancestral (D614G) strain following primary vaccination.
• mRNA-1273.351 appeared to be more effective at increasing neutralization titers against the B.1.351 variant when compared to mRNA-1273, as evidenced by higher mean GMT levels already at 15 days following booster dose (GMT = 1400 for mRNA-1273.351; GMT = 864 for mRNA-1273).
• mRNA-1273.351 booster also improved the relative decrease in neutralizing titers between the wild-type (D614G) and B.1.351 assays, from a 7.7-fold difference prior to boost to a 2.6-fold difference 15 days after boost, suggesting a potentially more balanced immune response against the tested variants.

Safety and tolerability profiles following third dose booster injections of 50 µg of mRNA-1273 or mRNA-1273.351 were generally comparable to those observed after the second dose of mRNA-1273 in the previously reported Phase 2 and Phase 3 studies.

A review of solicited adverse events indicated that the vaccine boosters were generally well tolerated. The majority of adverse events were mild or moderate in severity. The most common solicited local adverse event was injection site pain in both groups. The most common solicited systemic adverse events after the third dose of mRNA-1273.351 or mRNA-1273 were fatigue, headache, myalgia and arthralgia. In general, mRNA-1273.351 had a lower reactogenicity profile than mRNA-1273 in this study.

The ongoing phase II trial is evaluating the following three strategies for boosting neutralizing titers in previously vaccinated participants.

• mRNA-1273.351, a booster candidate based on the B.1.351 South Africa variant, mRNA-1273.211, a multivalent booster candidate which combines a 50-50 mix of mRNA-1273
• Moderna’s authorized vaccine against ancestral strains
• mRNA-1273.351 in a single vaccine, and a 50 µg booster dose of mRNA-1273. 

(Source: Moderna News release, May 5, 2021)

Dr KK Aggarwal

President CMAAO, HCFI and Past National President IMA