Larger booster dose dramatically increased antibodies compared to pre-boost levels

Moderna Inc. announced that booster doses of its mRNA-based Covid-19 vaccine, mRNA-1273, appeared to substantially increase neutralizing antibodies against the SARS-CoV-2 Omicron variant, with a new 100 μg booster offering the best protection.

According to the manufacturer, the currently authorized 50 μg mRNA-1273 booster bumped up patients’ neutralizing antibodies against Omicron roughly 37-fold compared to pre-boost levels—and the bigger 100 μg dose increased neutralizing antibodies around 83-fold.

While the company will continue to pursue development of a booster vaccine specifically geared towards the Omicron variant, “these data showing that the currently authorized Moderna Covid-19 booster can boost neutralizing antibody levels 37-fold higher than pre-boost levels are reassuring,” said Stéphane Bancel, CEO of Moderna, in a company press release.

The manufacturer previously explained that it plans to continuously work on new booster candidates in the event of new Covid variants of concern (VOC), a strategy that involves “evaluating the prototype vaccine (mRNA-1273) at the authorized booster dose (50 µg) and a higher dose (100 µg), multivalent candidates that incorporate previous VOCs (mRNA-1273.211, mRNA-1273.213) also at 50 µg and 100 µg, and VOC-specific booster candidates (Delta, Omicron).”

These latest data are based on an analysis of 100 booster recipients, of whom 20 participants each were given a booster of mRNA-1273 at the 50 μg and 100 μg dose levels, multivalent candidate mRNA-1273.211 at the 50 μg and 100 μg dose levels, and multivalent candidate mRNA-1273.213 at the 100 µg dose level. Researchers evaluated patients’ neutralizing antibody responses against Omicron using a pseudovirus neutralization titer (ID50) assay (PsVNT); assays were conducted at labs established by the National Institute of Allergy and Infectious Diseases’ Vaccine Research Center and Duke University Medical Center.

“All groups had low neutralizing antibody levels in the Omicron PsVNT assay prior to boosting,” the company explained. “At day 29 post boost, the authorized 50 µg booster of mRNA-1273 increased neutralizing geometric mean titers (GMT) against Omicron to 850, which is approximately 37-fold higher than pre-boost levels. At day 29 post boost, the 100 µg dose booster of mRNA-1273 increased neutralizing GMT to 2228, which is approximately 83-fold higher than pre-boost levels. The multivalent candidates boosted Omicron specific neutralizing antibody levels to similarly high levels at both the 50 µg and 100 µg levels. Based on the strength of neutralizing titers generated by mRNA-1273, the rapid pace of Omicron expansion, and the increased complexity of deploying a new vaccine, the Company will focus its near-term efforts to address Omicron on the mRNA-1273 booster. The Company will continue to assess the breadth and durability of neutralizing antibodies from the multivalent booster candidates in the months ahead.”

The company also pointed to results from its phase II/III study of the 100 μg booster of mRNA-1273 (n=305), which found that the larger booster dose was generally safe and well tolerated among participants. “The frequency and nature of solicited systemic and local adverse events 7 days after receiving a booster were generally comparable to those seen after the two-dose primary series,” the company wrote. “There was a trend toward slightly more frequent adverse reactions following the 100 µg booster dose relative to the authorized 50 µg booster dose of mRNA-1273.

“Moving forward, given the strength of the mRNA-1273 and the speed at which the Omicron variant is spreading, Moderna’s first line of defense against Omicron will be a booster dose of mRNA-1273,” the manufacturer added. “Given the long-term threat demonstrated by Omicron’s immune escape, Moderna will also continue to develop an Omicron-specific variant vaccine (mRNA-1273.529) that it expects to advance into clinical trials in early 2022 and will evaluate including Omicron in its multivalent booster program.”

John McKenna, Associate Editor, BreakingMED™

Cat ID: 31

Topic ID: 79,31,730,933,31,926,192,927,151,928,925,934