Beijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious Diseases, NHC Key Laboratory of Human Disease Comparative Medicine, Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
National Center of Technology Innovation for Animal Model, Beijing, China.
Animal Model Exp Med. 2023 Feb;6(1):51-56. doi: 10.1002/ame2.12302. Epub 2023 Feb 20.
New Omicron subvariants are emerging rapidly from BA.1 to BA.4 and BA.5. Their pathogenicity has changed from that of wild-type (WH-09) and Omicron variants have over time become globally dominant. The spike proteins of BA.4 and BA.5 that serve as the target for vaccine-induced neutralizing antibodies have also changed compared to the previous subvariants, which is likely to cause immune escape and the reduction of the protective effect of the vaccine. Our study addresses the above issues and provides a basis for formulating relevant prevention and control strategies.
We collected cellular supernatant and cell lysates and measured the viral titers, viral RNA loads, and E subgenomic RNA (E sgRNA) loads in different Omicron subvariants grown in Vero E6 cells, using WH-09 and Delta variants as a reference. Additionally, we evaluated the in vitro neutralizing activity of different Omicron subvariants and compared it to the WH-09 and Delta variants using macaque sera with different types of immunity.
As the SARS-CoV-2 evolved into Omicron BA.1, the replication ability in vitro began to decrease. Then with the emergence of new subvariants, the replication ability gradually recovered and became stable in the BA.4 and BA.5 subvariants. In WH-09-inactivated vaccine sera, geometric mean titers of neutralization antibodies against different Omicron subvariants declined by 3.715.4-fold compared to those against WH-09. In Delta-inactivated vaccine sera, geometric mean titers of neutralization antibodies against Omicron subvariants declined by 3.17.4-fold compared to those against Delta.
According to the findings of this research, the replication efficiency of all Omicron subvariants declined compared with WH-09 and Delta variants, and was lower in BA.1 than in other Omicron subvariants. After two doses of inactivated (WH-09 or Delta) vaccine, cross-neutralizing activities against various Omicron subvariants were seen despite a decline in neutralizing titers.
新的奥密克戎亚变种迅速从 BA.1 发展到 BA.4 和 BA.5。其致病性已经发生变化，与野生型（WH-09）相比，奥密克戎变体已经在全球范围内占据主导地位。与之前的亚变体相比，BA.4 和 BA.5 的刺突蛋白作为疫苗诱导的中和抗体的靶标也发生了变化，这可能导致免疫逃逸和疫苗保护作用的降低。我们的研究解决了上述问题，并为制定相关防控策略提供了依据。
我们收集了不同奥密克戎亚变种在 Vero E6 细胞中生长的细胞上清液和细胞裂解液，并测量了病毒滴度、病毒 RNA 载量和 E 亚基因组 RNA（E sgRNA）载量，以 WH-09 和 Delta 变体作为参考。此外，我们评估了不同奥密克戎亚变种的体外中和活性，并使用具有不同免疫类型的猕猴血清将其与 WH-09 和 Delta 变体进行了比较。
随着 SARS-CoV-2 进化为奥密克戎 BA.1，其体外复制能力开始下降。然后，随着新亚变种的出现，复制能力逐渐恢复，并在 BA.4 和 BA.5 亚变种中稳定下来。在 WH-09 灭活疫苗血清中，针对不同奥密克戎亚变种的中和抗体几何平均滴度与针对 WH-09 的中和抗体几何平均滴度相比下降了 3.715.4 倍。在 Delta 灭活疫苗血清中，针对奥密克戎亚变种的中和抗体几何平均滴度与针对 Delta 的中和抗体几何平均滴度相比下降了 3.17.4 倍。
根据本研究的结果，所有奥密克戎亚变种的复制效率均低于 WH-09 和 Delta 变体，BA.1 低于其他奥密克戎亚变种。在接种两剂灭活（WH-09 或 Delta）疫苗后，尽管中和滴度下降，但对各种奥密克戎亚变种仍具有交叉中和活性。
