Haars Jonathan, Wallin Frans, Elfving Karin, Jonsson Anna-Karin, Ellström Patrik, Mölling Paula, Lindh Johan, Yin Hong, Sundqvist Martin, Kaden René, Palanisamy Navaneethan, Lennerstrand Johan
Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Södra Grev Rosengatan, Örebro, Sweden.
Infect Dis (Lond). 2025 May 26:1-10. doi: 10.1080/23744235.2025.2509011.
Monoclonal antibodies (mAbs) are an important option against SARS-CoV-2, especially as pre-exposure prophylaxis (PrEP) for patients with immune system impairment. PrEP mAbs like sipavibart and pemivibart have been approved for limited use in several countries. Certain SARS-CoV-2 variants carry mutations in the spike (S) protein, conferring resistance to these mAbs.
We aimed to examine the relative abundance of different circulating SARS-CoV-2 variants/mutations in central Sweden between 2023 and 2024, and to predict the effectiveness of sipavibart and pemivibart.
An amplicon-based Nanopore sequencing method was used for sequencing SARS-CoV-2 samples. Coronapp was used to identify mutations in these sequences. Using the published resistance data for sipavibart and pemivibart, the effectiveness of these mAbs was inferred.
We have observed that the relative abundance of the KP.3.1.1 variant and the Q493E mutation started to increase in the later part of 2024 in the region. Also, since April 2024, the relative abundance of the F456L mutation reached 100% during many weeks until the end of the study period. The KP.3.1.1 variant is significantly resistant to pemivibart. Further, the presence of the F456L mutation in the Omicron subvariants confers high fold resistance towards sipavibart.
The use of sipavibart or pemivibart as PrEP for COVID-19 in the region may currently not be effective unless new SARS-CoV-2 variants appear not containing these resistance mutations. Further, new mAbs under development as PrEP for COVID-19 can be effectively used by routinely sequencing SARS-CoV-2 in patients to identify variants and resistance mutations.
单克隆抗体（mAbs）是对抗严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的重要选择，尤其是作为免疫系统受损患者的暴露前预防（PrEP）。西帕维巴特和培米维巴特等PrEP单克隆抗体已在多个国家获批有限使用。某些SARS-CoV-2变体在刺突（S）蛋白中携带突变，从而对这些单克隆抗体产生抗性。
我们旨在研究2023年至2024年瑞典中部不同循环SARS-CoV-2变体/突变的相对丰度，并预测西帕维巴特和培米维巴特的有效性。
采用基于扩增子的纳米孔测序方法对SARS-CoV-2样本进行测序。使用Coronapp识别这些序列中的突变。利用已发表的西帕维巴特和培米维巴特的抗性数据，推断这些单克隆抗体的有效性。
我们观察到，KP.3.1.1变体和Q493E突变的相对丰度在2024年下半年开始在该地区增加。此外，自2024年4月以来，在研究期结束前的许多周内，F456L突变的相对丰度达到了100%。KP.3.1.1变体对培米维巴特有显著抗性。此外，奥密克戎亚变体中F456L突变的存在赋予了对西帕维巴特的高倍数抗性。
目前，在该地区将西帕维巴特或培米维巴特用作COVID-19的PrEP可能无效，除非出现不包含这些抗性突变的新SARS-CoV-2变体。此外，正在开发的作为COVID-19 PrEP的新单克隆抗体可以通过对患者的SARS-CoV-2进行常规测序来有效识别变体和抗性突变。
