Safety and Immunogenicity of a 100 μg mRNA-1273 Vaccine Booster for Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2).

Abstract

Importance:

Due to the emergence of highly transmissible SARS-CoV-2 variants, evaluation of boosters is needed.

Objectives:

Evaluate safety and immunogenicity of 100-μg of mRNA-1273 booster dose in adults.

Design:

Open-label, Phase 2/3 study.

Setting:

Multicenter study at 8 sites in the U.S.

Participants:

The mRNA-1273 100-μg booster was administered to adults who previously received a two dose primary series of 100-μg mRNA-1273 in the phase 3 Coronavirus Efficacy (COVE) trial, at least 6 months earlier.

Intervention:

Lipid nanoparticle containing 100-μg of mRNA encoding the spike glycoprotein of SARS-CoV-2 (Wuhan-HU-1).

Main Outcomes and Measures:

Solicited local and systemic adverse reactions, and unsolicited adverse events were collected after vaccination. Primary immunogenicity objectives were to demonstrate non-inferiority of the neutralizing antibody (nAb) response against SARS-CoV-2 based on the geometric mean titer (GMTs) and the seroresponse rates (SRRs) (booster dose vs. primary series in a historical control group). nAbs against SARS-CoV-2 variants were also evaluated.

Results:

The 100-μg booster dose had a greater incidence of local and systemic adverse reactions compared to the second dose of mRNA-1273 as well as the 50-μg mRNA-1273 booster in separate studies. The geometric mean titers (GMTs; 95% CI) of SARS-CoV-2 nAbs against the ancestral SARS-CoV-2 at 28 days after the 100-μg booster dose were 4039.5 (3592.7,4541.8) and 1132.0 (1046.7,1224.2) at 28 days after the second dose in the historical control group [GMT ratio=3.6 (3.1,4.2)]. SRRs (95% CI) were 100% (98.6,100) at 28 days after the booster and 98.1% (96.7,99.1) 28 days after the second dose in the historical control group [percentage difference=1.9% (0.4,3.3)]. The GMT ratio (GMR) and SRR difference for the booster as compared to the primary series met the pre-specified non-inferiority criteria. Delta-specific nAbs also increased (GMT fold-rise=233.3) after the 100-μg booster of mRNA-1273.

Conclusions and Relevance:

The 100-μg mRNA-1273 booster induced a robust neutralizing antibody response against SARS-CoV-2, and reactogenicity was higher with the 100-μg booster dose compared to the authorized booster dose level in adults (50-μg). mRNA-1273 100-μg booster dose can be considered when eliciting an antibody response might be challenging such as in moderately or severely immunocompromised hosts.

Trial Registration:

NCT04927065.

• Authors: Spyros Chalkias, Howard Schwartz, Biliana Nestorova, Jing Feng, Ying Chang, Honghong Zhou, Frank J Dutko, Darin K Edwards, David Montefiori, Rolando Pajon, Brett Leav, Jacqueline M Miller, Rituparna Das
• Journal: medRxiv : the preprint server for health sciences (medRxiv) (Mar 07 2022) United States
• PMID: 35291289 (Publication Type: Preprint)