CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
Front Immunol. 2022 Jun 30;13:908478. doi: 10.3389/fimmu.2022.908478. eCollection 2022.
The newly emerged Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contains more than 30 mutations on the spike protein, 15 of which are located within the receptor binding domain (RBD). Consequently, Omicron is able to extensively escape existing neutralizing antibodies and may therefore compromise the efficacy of current vaccines based on the original strain, highlighting the importance and urgency of developing effective vaccines against Omicron. Here we report the rapid generation and evaluation of an mRNA vaccine candidate specific to Omicron, and explore the feasibility of heterologous immunization with WT and Omicron RBD vaccines. This mRNA vaccine encodes the RBD of Omicron (designated as RBD-O) and is formulated with lipid nanoparticle. Two doses of the RBD-O mRNA vaccine efficiently induce neutralizing antibodies in mice; however, the antisera are effective only on the Omicron variant but not on the wildtype and Delta strains, indicating a narrow neutralization spectrum. It is noted that the neutralization profile of the RBD-O mRNA vaccine is opposite to that observed for the mRNA vaccine expressing the wildtype RBD (RBD-WT). Importantly, booster with RBD-O mRNA vaccine after two doses of RBD-WT mRNA vaccine can significantly increase neutralization titers against Omicron. Additionally, an obvious increase in IFN-γ, IL-2, and TNF-α-expressing RBD-specific CD4 T cell responses was observed after immunization with the RBD-WT and/or RBD-O mRNA vaccine. Together, our work demonstrates the feasibility and potency of an RBD-based mRNA vaccine specific to Omicron, providing important information for further development of heterologous immunization program or bivalent/multivalent SARS-CoV-2 vaccines with broad-spectrum efficacy.
新出现的严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）的奥密克戎变体在刺突蛋白上含有超过 30 个突变，其中 15 个位于受体结合域（RBD）内。因此，奥密克戎能够广泛逃避现有的中和抗体，可能因此削弱基于原始毒株的现有疫苗的效力，凸显出针对奥密克戎开发有效疫苗的重要性和紧迫性。在这里，我们报告了一种针对奥密克戎的 mRNA 疫苗候选物的快速生成和评估，并探索了用 WT 和奥密克戎 RBD 疫苗进行异源免疫的可行性。该 mRNA 疫苗编码奥密克戎的 RBD（命名为 RBD-O），并与脂质纳米颗粒配制。两剂 RBD-O mRNA 疫苗能在小鼠中有效诱导中和抗体；然而，抗血清仅对奥密克戎变体有效，而对野生型和 Delta 株无效，表明中和谱较窄。值得注意的是，RBD-O mRNA 疫苗的中和谱与表达野生型 RBD（RBD-WT）的 mRNA 疫苗观察到的相反。重要的是，在两剂 RBD-WT mRNA 疫苗后用 RBD-O mRNA 疫苗加强免疫能显著提高针对奥密克戎的中和滴度。此外，用 RBD-WT 和/或 RBD-O mRNA 疫苗免疫后，观察到 IFN-γ、IL-2 和 TNF-α 表达的 RBD 特异性 CD4 T 细胞反应明显增加。总之，我们的工作证明了针对奥密克戎的基于 RBD 的 mRNA 疫苗的可行性和效力，为进一步开发异源免疫程序或具有广谱疗效的二价/多价 SARS-CoV-2 疫苗提供了重要信息。
