二价mRNA疫苗增强剂对K18-hACE2小鼠的XBB.1.5免疫比突破感染更有效

IF 4.1 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience Pub Date : 2025-09-01 DOI:10.1016/j.isci.2025.113479

Marissa E. Linger , Sytze H.T. Jorritsma , Jonna Bloeme-ter Horst , Jessika C. Zevenhoven-Dobbe , Finn Rijlaarsdam , Emil Colstrup , Macha Beijnes , Jutte J.C. de Vries , Ramon Arens , Rajagopal Murugan , Sebenzile K. Myeni , in collaboration with BREAK COVID group

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引用次数: 0

摘要

SARS-CoV-2 Omicron亚变体的迅速出现，包括高度免疫逃避的XBB.1.5谱系，继续挑战疫苗的有效性。我们评估了K18-hACE2小鼠在接受两剂或三剂二价mRNA疫苗（编码武汉-1和Omicron BA.4/5刺突）或两剂后鼻内暴露XBB.1.5的免疫反应和对XBB.1.5攻击的保护作用。与突破感染相比，二价疫苗同源增强能诱导更强的中和抗体和细胞免疫应答。单独的两剂系列可以保护小鼠免受严重疾病的侵害，但可以进一步增强保护，减少肺部病毒RNA和炎症。虽然鼻内暴露后的生产性感染尚未得到证实，但增强的反应和病毒控制表明免疫记忆的重新激活。总体而言，在幼稚小鼠模型中，二价疫苗的同源增强增强了跨变体免疫，并对XBB.1.5具有保护作用，支持更新疫苗在提高免疫广度和对新出现的SARS-CoV-2变体的保护方面的效用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Bivalent mRNA vaccine booster enhances immunity against XBB.1.5 more effectively than breakthrough infection in K18-hACE2 mice

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Bivalent mRNA vaccine booster enhances immunity against XBB.1.5 more effectively than breakthrough infection in K18-hACE2 mice

The rapid emergence of SARS-CoV-2 Omicron subvariants, including the highly immune-evasive XBB.1.5 lineage, continues to challenge vaccine effectiveness. We evaluated immune responses and protection against XBB.1.5 challenge in K18-hACE2 mice receiving two or three doses of a bivalent mRNA vaccine (encoding Wuhan-1 and Omicron BA.4/5 spike) or two doses followed by intranasal XBB.1.5 exposure. Homologous boosting with bivalent vaccine induced stronger neutralizing antibody and cellular immune responses than breakthrough infection against the antigenically distant XBB.1.5 variant. A two-dose series alone protected mice from severe disease, but boosting further enhanced protection, reducing lung viral RNA and inflammation. Although productive infection following intranasal exposure was not confirmed, enhanced responses and viral control suggest reactivation of immune memory. Overall, homologous boosting with the bivalent vaccine enhances cross-variant immunity and protects against XBB.1.5 in a naive mouse model, supporting the utility of updated vaccines in improving immune breadth and protection against emerging SARS-CoV-2 variants.

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来源期刊

iScience Multidisciplinary-Multidisciplinary

CiteScore

7.20

自引率

1.70%

发文量

1972

审稿时长

6 weeks

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