Giombini Emanuela, Schiavoni Ilaria, Ambrosio Luigina, Lo Presti Alessandra, Di Martino Angela, Fiore Stefano, Leone Pasqualina, Fortunato Francesca, Prato Rosa, Fedele Giorgio, Palamara Anna Teresa, Stefanelli Paola
Department of Infectious Diseases, Istituto Superiore Di Sanità, Rome, Italy.
Department of Medical and Surgical Sciences, Hygiene Unit, Policlinico Foggia Hospital, University of Foggia, Foggia, Italy.
BMC Infect Dis. 2025 Feb 28;25(1):291. doi: 10.1186/s12879-025-10685-0.
The continuous emergence of SARS-CoV-2 variants and subvariants poses significant public health challenges. The latest designated subvariant JN.1, with all its descendants, shows more than 30 mutations in the spike gene. JN.1 has raised concerns due to its genomic diversity and its potential to enhance transmissibility and immune evasion. This study aims to analyse the molecular characteristics of JN.1-related lineages (JN.1*) identified in Italy from October 2023 to April 2024 and to evaluate the neutralization activity against JN.1 of a subsample of sera from individuals vaccinated with XBB.1.5 mRNA.
The genomic diversity of the spike gene of 794 JN.1* strain was evaluated and phylogenetic analysis was conducted to compare the distance to XBB.1.5. Moreover, serum neutralization assays were performed on a subsample of 19 healthcare workers (HCWs) vaccinated with the monovalent XBB.1.5 mRNA booster to assess neutralizing capacity against JN.1.
Sequence analysis displayed high spike variability between JN.1* and phylogenetic investigation confirmed a substantial differentiation between JN.1* and XBB.1.5 spike regions with 29 shared mutations, of which 17 were located within the RBD region. Pre-booster neutralization activity against JN.1 was observed in 42% of HCWs sera, increasing significantly post-booster, with all HCWs showing neutralization capacity three months after vaccination. A significant correlation was found between anti-trimeric Spike IgG levels and neutralizing titers against JN.1.
The study highlights the variability of JN.1* in Italy. Results on a subsample of sera from HCWs vaccinated with XBB.1.5 mRNA booster vaccine suggested enhanced neutralization activity against JN.1.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）变异株和亚变异株的不断出现给公共卫生带来了重大挑战。最新指定的亚变异株JN.1及其所有后代在刺突基因中显示出30多个突变。JN.1因其基因组多样性及其增强传播性和免疫逃逸的潜力而引发关注。本研究旨在分析2023年10月至2024年4月在意大利鉴定出的与JN.1相关谱系（JN.1*）的分子特征，并评估接种XBB.1.5 mRNA疫苗个体血清亚样本对JN.1的中和活性。
评估了794株JN.1*毒株刺突基因的基因组多样性，并进行系统发育分析以比较与XBB.1.5的距离。此外，对19名接种单价XBB.1.5 mRNA加强针的医护人员血清亚样本进行了血清中和试验，以评估对JN.1的中和能力。
序列分析显示JN.1之间刺突变异度高，系统发育研究证实JN.1与XBB.1.5刺突区域存在显著差异，有29个共享突变，其中17个位于受体结合域（RBD）区域。42%的医护人员血清在加强免疫前观察到对JN.1的中和活性，加强免疫后显著增加，所有医护人员在接种疫苗三个月后均显示出中和能力。发现抗三聚体刺突IgG水平与针对JN.1的中和滴度之间存在显著相关性。
该研究突出了意大利JN.1*的变异性。接种XBB.1.5 mRNA加强疫苗的医护人员血清亚样本结果表明对JN.1的中和活性增强。
