Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan.
J Biomed Sci. 2022 Jul 7;29(1):49. doi: 10.1186/s12929-022-00830-1.
With the continuous emergence of new SARS-CoV-2 variants that feature increased transmission and immune escape, there is an urgent demand for a better vaccine design that will provide broader neutralizing efficacy.
We report an mRNA-based vaccine using an engineered "hybrid" receptor binding domain (RBD) that contains all 16 point-mutations shown in the currently prevailing Omicron and Delta variants.
A booster dose of hybrid vaccine in mice previously immunized with wild-type RBD vaccine induced high titers of broadly neutralizing antibodies against all tested SARS-CoV-2 variants of concern (VOCs). In naïve mice, hybrid vaccine generated strong Omicron-specific neutralizing antibodies as well as low but significant titers against other VOCs. Hybrid vaccine also elicited CD8+/IFN-γ+ T cell responses against a conserved T cell epitope present in wild type and all VOCs.
These results demonstrate that inclusion of different antigenic mutations from various SARS-CoV-2 variants is a feasible approach to develop cross-protective vaccines.
随着具有更高传播性和免疫逃逸能力的新型 SARS-CoV-2 变体不断出现，我们急需设计出一种更好的疫苗，以提供更广泛的中和效力。
我们报告了一种基于 mRNA 的疫苗，该疫苗使用经过工程改造的“混合”受体结合域（RBD），其中包含目前流行的奥密克戎和德尔塔变体中所有 16 个点突变。
先前用野生型 RBD 疫苗免疫的小鼠接种加强剂量的混合疫苗后，可诱导针对所有测试的 SARS-CoV-2 关注变体（VOC）的高滴度广谱中和抗体。在未经免疫的小鼠中，混合疫苗可产生针对奥密克戎的特异性中和抗体，以及针对其他 VOC 的低但有意义的滴度。混合疫苗还可诱导针对存在于野生型和所有 VOC 中的保守 T 细胞表位的 CD8+/IFN-γ+T 细胞反应。
这些结果表明，包含来自不同 SARS-CoV-2 变体的不同抗原突变是开发交叉保护疫苗的可行方法。
