Department of Immunology, Center for Innate Immunity and Immune Disease, University of Washington, Seattle, WA 98109, USA.
Center for Emerging & Re-Emerging Infectious Diseases, University of Washington, Seattle, WA 98109, USA.
Viruses. 2023 Feb 14;15(2):530. doi: 10.3390/v15020530.
New variants of SARS-CoV-2 continue to emerge and evade immunity. We isolated SARS-CoV-2 temporally across the pandemic starting with the first emergence of the virus in the western hemisphere and evaluated the immune escape among variants. A clinic-to-lab viral isolation and characterization pipeline was established to rapidly isolate, sequence, and characterize SARS-CoV-2 variants. A virus neutralization assay was applied to quantitate humoral immunity from infection and/or vaccination. A panel of novel monoclonal antibodies was evaluated for antiviral efficacy. We directly compared all variants, showing that convalescence greater than 5 months post-symptom onset from ancestral virus provides little protection against SARS-CoV-2 variants. Vaccination enhances immunity against viral variants, except for Omicron BA.1, while a three-dose vaccine regimen provides over 50-fold enhanced protection against Omicron BA.1 compared to a two-dose. A novel Mab neutralizes Omicron BA.1 and BA.2 variants better than the clinically approved Mabs, although neither can neutralize Omicron BA.4 or BA.5. Thus, the need remains for continued vaccination-booster efforts, with innovation for vaccine and Mab improvement for broadly neutralizing activity. The usefulness of specific Mab applications links with the window of clinical opportunity when a cognate viral variant is present in the infected population.
新的 SARS-CoV-2 变体不断出现并逃避免疫。我们从病毒在西半球首次出现开始，在整个大流行期间对 SARS-CoV-2 变体进行了时间上的分离和评估，以评估其免疫逃逸能力。建立了一个从临床到实验室的病毒分离和特征分析管道，以快速分离、测序和分析 SARS-CoV-2 变体。应用病毒中和测定法来定量感染和/或接种疫苗后的体液免疫。评估了一组新型单克隆抗体的抗病毒功效。我们直接比较了所有变体，结果表明，从最初的病毒感染后超过 5 个月的恢复期对 SARS-CoV-2 变体提供的保护作用很小。接种疫苗增强了对病毒变体的免疫力，除了 Omicron BA.1 之外，而三剂疫苗方案对 Omicron BA.1 的保护作用比两剂疫苗增强了 50 多倍。一种新型 Mab 对 Omicron BA.1 和 BA.2 变体的中和作用优于临床批准的 Mab，尽管两者都不能中和 Omicron BA.4 或 BA.5。因此，需要继续进行疫苗接种增强工作，并进行疫苗和 Mab 的创新，以提高广泛中和活性。特定 Mab 应用的有效性与感染人群中存在同源病毒变体的临床机会窗口有关。
