Moderna Releases Positive Initial COVID-19 Vaccine Booster Data Against Variants of Concern

Initial data from a phase 2 study showed that a single 50 µg dose of COVID-19 vaccines mRNA-1273 or mRNA-1273.351 given as a booster to individuals who were previously vaccinated increased their neutralizing antibody titer responses against SARS-CoV-2. The vaccines also improved the antibody titer responses against 2 variants of concern, the B.1.351 variant that was first identified in South Africa and the P.1 variant that was first identified in Brazil.

During the trial, the investigators observed that a booster dose of mRNA-1273.351, a strain-matched booster Moderna developed for use against the B.1.351 variant, was found to achieve a higher level of neutralizing antibody titers against the B.1.351 variant than a booster dose of mRNA-1273 alone.

“We are encouraged by these new data, which reinforce our confidence that our booster strategy should be protective against these newly detected variants. The strong and rapid boost in titers to levels above primary vaccination also clearly demonstrates the ability of mRNA-1273 to induce immune memory,” said Stéphane Bancel, chief executive officer of Moderna, in a press release.

Bancel noted that the mRNA platform specifically allows for these types of quick design changes to vaccine candidates that allow for incorporating targets against key virus mutations as necessary. He explained that this ability to rapidly adapt to changes in the virus may allow for faster development of future alternative variant-matched vaccines as well.

“We look forward to sharing data on our multivalent booster candidate, mRNA-1273.211, which combines mRNA-1273 and mRNA-1273.351 in a single vaccine, when available,” Bancel said in the press release. “We will continue to make as many updates to our COVID-19 vaccine as necessary to control the pandemic.”

During the study, the investigators tested 3 different vaccine strategies for boosting neutralizing titers in previously vaccinated participants. The first strategy was using the booster candidate mRNA-1273.351, which was developed to target the B.1.351 variant first identified in the Republic of South Africa.

The second method was using the multivalent booster candidate mRNA-1273.211, which is a 50-50 mix of mRNA-1273 and mRNA-1273.351, in a single vaccine. The third strategy tested was using a single 50 µg booster dose of mRNA-1273.

Based on preliminary data 2 weeks following the administration of a booster dose of mRNA-1273 or mRNA-1273.351, the investigators were able to compile data for their initial analysis. Furthermore, additional samples are ongoing and planned for collection later during the trial for the multivalent vaccine candidate, mRNA-1273.211, and for a lower dose of mRNA-1273.351. In the study, trial participants were tested for pseudovirus neutralization (PsVN) titers before the boosters were administered and approximately 6 to 8 months after their primary vaccination series.

Upon analysis, the investigators found that PsVN titers were quite high compared with the wild-type SARS-CoV-2 virus, with 37 of 40 participants having detectable titers. However, titers against the variants of concern, such as B.1.351 and P.1, were significantly lower, with approximately half of participants presenting with titers below the assay limit of quantification before they were given the booster.

Two weeks following a booster shot of either mRNA-1273 or mRNA-1273.351, investigators boosted PsVN titers in all participants and tested for all potential variants. The investigators then tested for the geometric mean titers (GMT) in comparison with the wild-type, B.1.351. They found that P.1 variants had increased to levels that were close to or greater than the peak titers that were previously reported against the D614G ancestral strain, which were recorded following participants’ primary vaccination series.

The initial data showed that the mRNA-1273.351 booster demonstrates greater efficacy at increasing neutralization titers against the B.1.351 variant in comparison with mRNA-1273. This was demonstrated based on the higher mean GMT levels at 15 days following the booster dose (GMT = 1400 for mRNA-1273.351; GMT = 864 for mRNA-1273).

Additionally, the decrease in neutralizing titers between the D614G wild-type and B.1.351 variant assays also improved following the mRNA-1273.351 booster, from a 7.7-fold difference before the booster administration compared with a 2.6-fold difference 15 days after the booster. The investigators noted that this may show a more balanced immune response against the tested variants for this booster.

The safety and tolerability of the third dose booster injections of 50 µg of mRNA-1273 or mRNA-1273.351 were found to be generally comparable to those observed following the second dose of mRNA-1273 during the prior phase 2 and 3 studies. A review of these studies showed that adverse events (AEs) following the vaccine boosters were generally well tolerated, with the majority being mild to moderate in severity.

Grade 3 solicited local or systemic AEs occurred at a frequency of 15% following the third dose of mRNA-1273, and a rate of 10.5% following the third dose of mRNA-1273.351. Notably, no grade 4 local or systemic AEs were observed in trial participants.

In both study groups, the most common solicited local AE was injection site pain, whereas the most common solicited systemic AEs following the third dose of mRNA-1273.351 or mRNA-1273 were fatigue, headache, myalgia, and arthralgia. Overall, the investigators found that the mRNA-1273.351 booster had a lower reactogenicity profile than the mRNA-1273 booster in this study.

REFERENCE

Moderna Announces Positive Initial Booster Data Against SARS-CoV-2 Variants of Concern. Cambridge, MA: Moderna; May 5, 2021. https://www.businesswire.com/news/home/20210505006025/en. Accessed May 7, 2021.