Wang Gang, Verma Abhishek K, Shi Juan, Guan Xiaoqing, Meyerholz David K, Bu Fan, Wen Wei, Liu Bin, Li Fang, Perlman Stanley, Du Lanying
Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA.
Department of Microbiology and Immunology, University of Iowa, Iowa City, IA, USA.
NPJ Vaccines. 2024 Jul 25;9(1):133. doi: 10.1038/s41541-024-00922-z.
Although Omicron RBD of SARS-CoV-2 accumulates many mutations, the backbone region (truncated RBD) of spike protein is highly conserved. Here, we designed several subunit vaccines by keeping the conserved spike backbone region of SARS-CoV-2 Omicron BA.1 subvariant (S-6P-no-RBD), or inserting the RBD of Delta variant (S-6P-Delta-RBD), Omicron (BA.5) variant (S-6P-BA5-RBD), or ancestral SARS-CoV-2 (S-6P-WT-RBD) to the above backbone construct, and evaluated their ability to induce immune responses and cross-protective efficacy against various SARS-CoV-2 variants and SARS-CoV. Among the four subunit vaccines, S-6P-Delta-RBD protein elicited broad and potent neutralizing antibodies against all SARS-CoV-2 variants tested, including Alpha, Beta, Gamma, and Delta variants, the BA.1, BA.2, BA.2.75, BA.4.6, and BA.5 Omicron subvariants, and the ancestral strain of SARS-CoV-2. This vaccine prevented infection and replication of SARS-CoV-2 Omicron, and completely protected immunized mice against lethal challenge with the SARS-CoV-2 Delta variant and SARS-CoV. Sera from S-6P-Delta-RBD-immunized mice protected naive mice against challenge with the Delta variant, with significantly reduced viral titers and without pathological effects. Protection correlated positively with the serum neutralizing antibody titer. Overall, the designed vaccine has potential for development as a universal COVID-19 vaccine and/or a pan-sarbecovirus subunit vaccine that will prevent current and future outbreaks caused by SARS-CoV-2 variants and SARS-related CoVs.
尽管新冠病毒奥密克戎毒株的受体结合结构域（RBD）积累了许多突变，但刺突蛋白的主干区域（截短的RBD）高度保守。在此，我们通过保留新冠病毒奥密克戎BA.1亚变体（S-6P-no-RBD）的保守刺突主干区域，或将德尔塔变体的RBD（S-6P-Delta-RBD）、奥密克戎（BA.5）变体的RBD（S-6P-BA5-RBD）或新冠病毒原始毒株的RBD（S-6P-WT-RBD）插入上述主干构建体，设计了几种亚单位疫苗，并评估了它们诱导免疫反应以及针对各种新冠病毒变体和严重急性呼吸综合征冠状病毒（SARS-CoV）的交叉保护效力。在这四种亚单位疫苗中，S-6P-Delta-RBD蛋白引发了针对所有测试的新冠病毒变体的广泛而强效的中和抗体，包括阿尔法、贝塔、伽马和德尔塔变体、BA.1、BA.2、BA.2.75、BA.4.6和BA.5奥密克戎亚变体以及新冠病毒原始毒株。这种疫苗预防了新冠病毒奥密克戎毒株的感染和复制，并完全保护免疫小鼠免受新冠病毒德尔塔变体和SARS-CoV致死性攻击。来自接种S-6P-Delta-RBD疫苗小鼠的血清保护未感染小鼠免受德尔塔变体攻击，病毒滴度显著降低且无病理效应。保护作用与血清中和抗体滴度呈正相关。总体而言，所设计的疫苗有潜力开发成为一种通用的新冠疫苗和/或泛沙贝病毒亚单位疫苗，可预防由新冠病毒变体和SARS相关冠状病毒引起的当前及未来疫情爆发。
