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持续追踪以有效应对:基于Ad5/35平台的JN1谱系疫苗研发以应对不断演变的SARS-CoV-2变体

Continuous Tracking for Effective Tackling: Ad5/35 Platform-Based JN1 Lineage Vaccines Development in Response to Evolving SARS-CoV-2 Variants.

作者信息

Chang Soojeong, Shin Jieun, Park Seowoo, Park Hyemin, Kim Jong Heon, Kim Tae Wan, Jung In Kyung, Song Boyeong, Shin Kwang-Soo, Park Bongju, Kim Seo-Yeon, Jeon Ji Hyang, Yeo Jinah, Lee Tae-Young, Kang Chang-Yuil

机构信息

Research & Development Center, Cellid Co. Ltd., Seoul, South Korea.

Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, South Korea.

出版信息

J Med Virol. 2025 Feb;97(2):e70206. doi: 10.1002/jmv.70206.

DOI:10.1002/jmv.70206
PMID:39891605
Abstract

The SARS-CoV-2 virus is continuously evolving, such that JN.1 and its subvariants, including KP.2, KP.3, and LB.1, are now predominant variants globally. JN.1 is derived from BA.2.86, which harbors more than 30 mutations in the spike protein compared with those of XBB and BA.2, and it carries an additional L455S mutation. Given the rapid evolution of these variants, assessing the neutralization capacity of current JN.1 lineage vaccines against prevalent variants, such as KP.3, is critical. Phylogenetic trees using spike protein sequences and antigenic cartography based on neutralization results reveal that JN.1 lineage variants are antigenically distant from previously circulating variants. Moreover, JN.1 subvariants showed inadequate neutralization titers compared with other variants against XBB.1.5-containing vaccine in mice. Immunization with vaccines targeting the JN.1, KP.2, KP.3, and LB.1 variants demonstrated significant neutralizing activity against predominant variants in mice. These results highlight the importance of vaccine development to keep pace with the evolution of SARS-CoV-2 variants and the need for updated vaccines targeting the JN.1 variant.

摘要

严重急性呼吸综合征冠状病毒2(SARS-CoV-2)病毒在不断进化,以至于JN.1及其亚变体,包括KP.2、KP.3和LB.1,现在成为全球主要变体。JN.1源自BA.2.86,与XBB和BA.2相比,其刺突蛋白携带30多个突变,并且还带有一个额外的L455S突变。鉴于这些变体的快速进化,评估当前JN.1谱系疫苗对流行变体(如KP.3)的中和能力至关重要。使用刺突蛋白序列构建的系统发育树以及基于中和结果的抗原图谱显示,JN.1谱系变体在抗原性上与先前流行的变体存在差异。此外,与其他变体相比,JN.1亚变体在小鼠体内针对含XBB.1.5的疫苗表现出不足的中和滴度。用针对JN.1、KP.2、KP.3和LB.1变体的疫苗进行免疫接种在小鼠体内显示出对主要变体具有显著的中和活性。这些结果凸显了疫苗研发跟上SARS-CoV-2变体进化步伐的重要性,以及针对JN.1变体研发更新疫苗的必要性。

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