Hauser David, Urda Lorena, Lang Christopher, Mittelholzer Christian, Otte Fabian, Kipfer Enja, Zhang Yuepeng, Lett Martin, Schebitz Christiane, Müller Roman-Ulrich, Klimkait Wilfried, Klimkait Thomas
Molecular Virology, Department of Biomedicine, University of Basel, Basel, Switzerland.
Gemeinschaftspraxis Martinstrasse, Kinder- und Jugendmedizin, Olpe, Germany.
Open Forum Infect Dis. 2024 Sep 9;11(10):ofae527. doi: 10.1093/ofid/ofae527. eCollection 2024 Oct.
Current COVID-19 vaccines primarily target the Spike protein of defined virus variants, offering limited protection against emerging variants in immunocompetent individuals. Similarly, protective immunity following natural SARS-CoV-2 infection is variable and of short duration, raising concerns about immunocompromised individuals' vaccination strategies.
This prospective multicenter study examined 66 sera from 59 immunocompromised and 451 sera from 215 immunocompetent individuals from different pandemic periods. We establish and validate a live virus-based neutralization assay to determine the virus-inactivating potential against ancestral and current SARS-CoV-2 isolates.
Our virus-based neutralization assay demonstrated superior performance over surrogate neutralization assays. We found strong but transient immunity after complete vaccination schemes, with single doses providing minimum neutralization, regardless of vaccine type. Combining vaccination-induced immunity with SARS-CoV-2 infection before or after vaccination yielded higher neutralizing titers than vaccination or infection alone, consistent across both study groups. Additional doses after a full vaccination course restored neutralization levels.
Potentially protective SARS-CoV-2 neutralization is reliably induced in immunocompromised individuals by prior attenuation of immunosuppression. First-generation vaccines protect against various SARS-CoV-2 variants in immunocompetent individuals, with effective cross-neutralization demonstrated up to the Delta variant but largely absent for later Omicron variants. Continuous vaccine updates are necessary to address emerging SARS-CoV-2 variants.
目前的新冠病毒疫苗主要针对特定病毒变体的刺突蛋白，对免疫功能正常个体中出现的变体提供的保护有限。同样，自然感染新冠病毒后的保护性免疫也存在差异且持续时间短，这引发了对免疫功能低下个体疫苗接种策略的担忧。
这项前瞻性多中心研究检测了来自不同疫情时期的59名免疫功能低下个体的66份血清以及215名免疫功能正常个体的451份血清。我们建立并验证了一种基于活病毒的中和试验，以确定对原始毒株和当前新冠病毒分离株的病毒灭活潜力。
我们基于病毒的中和试验表现优于替代中和试验。我们发现，在完成疫苗接种方案后有强大但短暂的免疫力，单剂量提供的中和作用最小，无论疫苗类型如何。将疫苗接种诱导的免疫与接种疫苗前后的新冠病毒感染相结合，产生的中和滴度高于单独接种疫苗或感染，两个研究组均一致。完整疫苗接种疗程后额外接种剂量可恢复中和水平。
通过事先减轻免疫抑制，在免疫功能低下个体中可可靠诱导具有潜在保护作用的新冠病毒中和作用。第一代疫苗可保护免疫功能正常个体免受各种新冠病毒变体感染，对德尔塔变体显示出有效的交叉中和作用，但对后来的奥密克戎变体则基本没有。需要持续更新疫苗以应对新出现的新冠病毒变体。
