Adjuvanted soluble protein vaccines have been used extensively in humans for protection against various viral infections based on their robust induction of antibody responses. Here, soluble prefusion-stabilized spike protein trimers (preS dTM) from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were formulated with the adjuvant AS03 and administered twice to nonhuman primates (NHPs). Binding and functional neutralization assays and systems serology revealed that the vaccinated NHP developed AS03-dependent multifunctional humoral responses that targeted distinct domains of the spike protein and bound to a variety of Fc receptors mediating immune cell effector functions in vitro. The neutralizing 50% inhibitory concentration titers for pseudovirus and live SARS-CoV-2 were higher than titers for a panel of human convalescent serum samples. NHPs were challenged intranasally and intratracheally with a high dose (3 × 10⁶ plaque forming units) of SARS-CoV-2 (USA-WA1/2020 isolate). Two days after challenge, vaccinated NHPs showed rapid control of viral replication in both the upper and lower airways. Vaccinated NHPs also had increased spike protein–specific immunoglobulin G (IgG) antibody responses in the lung as early as 2 days after challenge. Moreover, passive transfer of vaccine-induced IgG to hamsters mediated protection from subsequent SARS-CoV-2 challenge. These data show that antibodies induced by the AS03-adjuvanted preS dTM vaccine were sufficient to mediate protection against SARS-CoV-2 in NHPs and that rapid anamnestic antibody responses in the lung may be a key mechanism for protection.

佐剂可溶性蛋白疫苗已广泛用于人类，以基于其对抗体反应的强烈诱导来防止各种病毒感染。在这里，来自严重急性呼吸系统综合症冠状病毒 2 (SARS-CoV-2) 的可溶性预融合稳定刺突蛋白三聚体 (preS dTM) 与佐剂 AS03 一起配制，并两次施用于非人灵长类动物 (NHP)。结合和功能中和分析以及系统血清学表明，接种疫苗的 NHP 产生了依赖于 AS03 的多功能体液反应，该反应针对刺突蛋白的不同结构域，并与多种 Fc 受体结合，在体外介导免疫细胞效应子功能。假病毒和活 SARS-CoV-2 的中和 50% 抑制浓度滴度高于一组人类恢复期血清样本的滴度。NHPs 在鼻内和气管内接受高剂量（3 × 10^{6 个}斑块形成单位）的 SARS-CoV-2（USA-WA1/2020 分离株）。攻击后两天，接种疫苗的 NHP 显示出对上呼吸道和下呼吸道病毒复制的快速控制。早在攻击后 2 天，接种疫苗的 NHP 肺部的刺突蛋白特异性免疫球蛋白 G (IgG) 抗体反应也有所增加。此外，疫苗诱导的 IgG 被动转移到仓鼠介导了对随后的 SARS-CoV-2 攻击的保护。这些数据表明，由 AS03 佐剂的 preS dTM 疫苗诱导的抗体足以介导 NHP 中针对 SARS-CoV-2 的保护作用，并且肺中的快速记忆抗体反应可能是保护作用的关键机制。