重复接种疫苗对奥密克戎亚变体中和抗体反应的有限免疫印记。

Finite immune imprinting on neutralizing antibody responses to Omicron subvariants by repeated vaccinations.

机构信息

State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, Beijing, China; Department of Laboratory Medicine, Handan Central Hospital, Hebei Medical University, Handan, China; Hebei Key Laboratory of Immune Mechanism of Major Infectious Diseases and New Technology of Diagnosis and Treatment, The Fifth Hospital of Shijiazhuang, Hebei Medical University, Shijiazhuang, China.

Department of Microbiological Laboratory Technology, School of Public Health, Cheeloo College of Medicine, Shandong University, Key Laboratory of Prevention and Control of Emerging Infectious Diseases and Biosafety in Universities of Shandong, Jinan, China.

出版信息

Int J Infect Dis. 2024 Oct;147:107198. doi: 10.1016/j.ijid.2024.107198. Epub 2024 Aug 6.

DOI:10.1016/j.ijid.2024.107198

PMID:39117174

Abstract

OBJECTIVE

To investigate the effects of repeated vaccination with ancestral SARS-CoV-2 (Wuhan-hu-1)-based inactivated, recombinant protein subunit or vector-based vaccines on the neutralizing antibody response to Omicron subvariants.

METHODS

Individuals who received four-dose vaccinations with the Wuhan-hu-1 strain, individuals who were infected with the BA.5 variant alone without prior vaccination, and individuals who experienced a BA.5 breakthrough infection (BTI) following receiving 2-4 doses of the Wuhan-hu-1 vaccine were enrolled. Neutralizing antibodies against D614G, BA.5, XBB.1.5, EG.5.1, and BA.2.86 were detected using a pseudovirus-based neutralization assay. Antigenic cartography was used to analyze cross-reactivity patterns among D614G, BA.5, XBB.1.5, EG.5.1, and BA.2.86 and sera from individuals.

RESULTS

The highest neutralizing antibody titers against D614G were observed in individuals who only received four-dose vaccination and those who experienced BA.5 BTI, which was also significantly higher than the antibody titers against XBB.1.5, EG.5.1, and BA.2.86. In contrast, only BA.5 infection elicited comparable neutralizing antibody titers against the tested variants. While neutralizing antibody titers against D614G or BA.5 were similar across the cohorts, the neutralizing capacity of antibodies against XBB.1.5, EG.5.1, and BA.2.86 was significantly reduced. BA.5 BTI following heterologous booster induced significantly higher neutralizing antibody titers against the variants, particularly against XBB.1.5 and EG.5.1, than uninfected vaccinated individuals, only BA.5 infected individuals, or those with BA.5 BTI after primary vaccination.

CONCLUSIONS

Our findings suggest that repeated vaccination with the Wuhan-hu-1 strain imprinted a neutralizing antibody response toward the Wuhan-hu-1 strain with limited effects on the antibody response to the Omicron subvariants.

摘要

目的

研究重复接种基于原始 SARS-CoV-2（武汉株）的灭活疫苗、重组蛋白亚单位疫苗或基于载体的疫苗对奥密克戎亚变体的中和抗体应答的影响。

方法

本研究纳入了接受了 4 剂武汉株疫苗接种的个体、未接种疫苗但单独感染 BA.5 变异株的个体、以及在接种 2-4 剂武汉株疫苗后发生 BA.5 突破性感染（BTI）的个体。使用假病毒中和试验检测针对 D614G、BA.5、XBB.1.5、EG.5.1 和 BA.2.86 的中和抗体。抗原绘图用于分析 D614G、BA.5、XBB.1.5、EG.5.1 和 BA.2.86 之间以及个体血清中的交叉反应模式。

结果

仅接受 4 剂疫苗接种和发生 BA.5 BTI 的个体对 D614G 的中和抗体滴度最高，明显高于对 XBB.1.5、EG.5.1 和 BA.2.86 的抗体滴度。相比之下，只有 BA.5 感染才能引起针对所测试变体的可比中和抗体滴度。虽然 D614G 或 BA.5 的中和抗体滴度在各队列中相似，但对 XBB.1.5、EG.5.1 和 BA.2.86 的抗体中和能力显著降低。异源加强后发生 BA.5 BTI 会引起针对变体的中和抗体滴度显著升高，特别是针对 XBB.1.5 和 EG.5.1，明显高于未感染的接种个体、仅感染 BA.5 的个体或在初次接种后发生 BA.5 BTI 的个体。