The emergence of SARS-CoV-2 variants of concern (VOCs) and variants of interest (VOIs) with decreased susceptibility to neutralization has generated interest in assessments of booster doses and variant-specific vaccines. Clinical trial participants who received a two-dose primary series of the COVID-19 vaccine mRNA-1273 approximately 6 months earlier entered an open-label phase 2a study ( NCT04405076 ) to evaluate the primary objectives of safety and immunogenicity of a single booster dose of mRNA-1273 or variant-modified mRNAs, including multivalent mRNA-1273.211. As the trial is currently ongoing, this exploratory interim analysis includes preliminary descriptive results only of four booster groups ( n = 20 per group). Immediately before the booster dose, neutralizing antibodies against wild-type D614G virus had waned ( P < 0.0001) relative to peak titers against wild-type D614G measured 1 month after the primary series, and neutralization titers against B.1.351 (Beta), P.1 (Gamma) and B.1.617.2 (Delta) VOCs were either low or undetectable. Both the mRNA-1273 booster and variant-modified boosters were safe and well-tolerated. All boosters, including mRNA-1273, numerically increased neutralization titers against the wild-type D614G virus compared to peak titers against wild-type D614G measured 1 month after the primary series; significant increases were observed for mRNA-1273 and mRNA-1273.211 ( P < 0.0001). In addition, all boosters increased neutralization titers against key VOCs and VOIs, including B.1.351, P.1. and B.1.617.2, that were statistically equivalent to peak titers measured after the primary vaccine series against wild-type D614G virus, with superior titers against some VOIs. This trial is ongoing. Preliminary and exploratory analyses show that a third dose of the COVID-19 vaccine mRNA-1273 or variant-modified boosters can boost levels of neutralizing antibodies against SARS-CoV-2 variants.
【저자키워드】 RNA vaccines, 【초록키워드】 neutralizing antibody, Vaccine, COVID-19 vaccine, immunogenicity, Trial, Open-label, Neutralizing antibodies, VoC, B.1.351, mRNA-1273, neutralization, susceptibility, variant, SARS-CoV-2 variant, Delta, B.1.617.2, variants, SARS-CoV-2 variants, mRNA, P.1, clinical, VOCs, Gamma, variants of interest, Beta, VOIs, assessment, group, booster dose, booster, boost, neutralization titers, dose, titers, Safe, (Beta), booster doses, assessments, significant increase, Exploratory analysis, Exploratory analyses, COVID-19 vaccine mRNA-1273, mRNA-1273.211, multivalent mRNA-1273.211, open-label phase 2a study, single booster dose, variant-modified boosters, variant-modified mRNAs, variant-specific vaccines, wild-type D614G, wild-type D614G virus, neutralization titer, mRNA-1273 booster, evaluate, include, addition, statistically, exploratory interim analysis, trial participant, undetectable, variant-modified booster, waned, 【제목키워드】 Safety, mRNA vaccine, SARS-CoV-2 variant, booster, interim analysis, healthy,