Department of Pathology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.
Center for Surveillance, Immunization, and Epidemiologic Research, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.
Med. 2022 Apr 8;3(4):249-261.e4. doi: 10.1016/j.medj.2022.02.006. Epub 2022 Mar 4.
The immune profile against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has dramatically diversified due to a complex combination of exposure to vaccines and infection by various lineages/variants, likely generating a heterogeneity in protective immunity in a given population. To further complicate this, the Omicron variant, with numerous spike mutations, has emerged. These circumstances have created the need to assess the potential of immune evasion by Omicron in individuals with various immune histories.
The neutralization susceptibility of the variants, including Omicron and their ancestors, was comparably assessed using a panel of plasma/serum derived from individuals with divergent immune histories. Blood samples were collected from either mRNA vaccinees or from those who suffered from breakthrough infections of Alpha/Delta with multiple time intervals following vaccination.
Omicron was highly resistant to neutralization in fully vaccinated individuals without a history of breakthrough infections. In contrast, robust cross-neutralization against Omicron was induced in vaccinees that experienced breakthrough infections. The time interval between vaccination and infection, rather than the variant types of infection, was significantly correlated with the magnitude and potency of Omicron-neutralizing antibodies.
Immune histories with breakthrough infections can overcome the resistance to infection by Omicron, with the vaccination-infection interval being the key determinant of the magnitude and breadth of neutralization. The diverse exposure history in each individual warrants a tailored and cautious approach to understanding population immunity against Omicron and future variants.
This study was supported by grants from the Japan Agency for Medical Research and Development (AMED).
由于疫苗接种和各种谱系/变体感染的复杂组合，针对严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 的免疫谱发生了巨大变化，这可能在特定人群中产生了保护免疫的异质性。为了使情况进一步复杂化，出现了具有大量刺突突变的奥密克戎变体。这些情况使得有必要评估奥密克戎在具有不同免疫史的个体中逃避免疫的可能性。
使用来自具有不同免疫史的个体的血浆/血清的面板，对变体（包括奥密克戎及其祖先）的中和敏感性进行了可比评估。从接受 mRNA 疫苗接种的个体或从那些在接种疫苗后多个时间间隔经历 Alpha/Delta 突破性感染的个体中采集血液样本。
奥密克戎在没有突破性感染史的完全接种疫苗的个体中高度抵抗中和。相比之下，在经历突破性感染的疫苗接种者中，对奥密克戎产生了强大的交叉中和。接种疫苗和感染之间的时间间隔，而不是感染的变体类型，与奥密克戎中和抗体的幅度和效力显著相关。
具有突破性感染史的免疫可以克服对奥密克戎感染的抵抗力，接种疫苗和感染之间的间隔是中和幅度和广度的关键决定因素。每个人的不同暴露史需要对理解奥密克戎和未来变体的人群免疫有针对性和谨慎的方法。
本研究得到了日本医疗研究与发展机构（AMED）的资助。
