Discovery Biologics Department, Research Division, Chugai Pharmaceutical Co., Ltd., Kamakura, Kanagawa, Japan.
Protein Analysis Unit, Research Division, Chugai Pharmabody Research Pte. Ltd, Singapore.
MAbs. 2022 Jan-Dec;14(1):2040350. doi: 10.1080/19420862.2022.2040350.
The emergence of escape variants of SARS-CoV-2 carrying mutations in the spike protein poses a challenge for therapeutic antibodies. Here, we show that through the comprehensive engineering of the variable region of the neutralizing monoclonal antibody 5A6, the engineered antibody, 5A6CCS1, is able to neutralize SARS-CoV-2 variants that escaped neutralization by the original 5A6 antibody. In addition to the improved affinity against variants, 5A6CCS1 was also optimized to achieve high solubility and low viscosity, enabling a high concentration formulation for subcutaneous injection. In cynomolgus monkeys, 5A6CCS1 showed a long plasma half-life and good subcutaneous bioavailability through engineering of the variable and constant region. These data demonstrate that 5A6CCS1 is a promising antibody for development against SARS-CoV-2 and highlight the importance of antibody engineering as a potential method to counteract escape variants.
SARS-CoV-2 棘突蛋白突变逃逸变异株的出现给治疗性抗体带来了挑战。在这里，我们展示了通过对中和单克隆抗体 5A6 的可变区进行全面工程改造，工程化抗体 5A6CCS1 能够中和被原始 5A6 抗体逃逸中和的 SARS-CoV-2 变异株。除了提高对变异株的亲和力外，5A6CCS1 还经过优化以实现高溶解性和低粘度，从而能够实现皮下注射的高浓度配方。在食蟹猴中，通过可变区和恒定区的工程改造，5A6CCS1 表现出长血浆半衰期和良好的皮下生物利用度。这些数据表明，5A6CCS1 是一种有前途的针对 SARS-CoV-2 的开发抗体，并强调了抗体工程作为对抗逃逸变异株的潜在方法的重要性。
