Safety and immunogenicity of SARS-CoV-2 variant mRNA vaccine boosters in healthy adults: an interim analysis

作者：Angela Choi, Matthew A. Koch, Kaichun Wu, Laurence Chu, LingZhi Ma, A V Hill, Naveen Nunna, Wenmei Huang, Judy Oestreicher, Tonya Michelle Colpitts, Hamilton Bennett, Holly M. Legault, Yamuna Devi Paila, Biliana Nestorova, Baoyu Ding, David C. Montefiori, Rolando Pajón, Jacqueline M. Miller, Brett A. Leav, Andrea Carfı́, Roderick A. McPhee, Darin K. Edwards · 发表于：Nature Medicine · 年份：2021 · DOI：10.1038/s41591-021-01527-y · 被引用次数：450 · 研究领域：SARS-CoV-2 and COVID-19 Research、SARS-CoV-2 detection and testing、Viral Infections and Immunology Research

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 ...