Department of Genome Sciences, University of Washington , Seattle, Washington, USA.
Medical Scientist Training Program, University of Washington , Seattle, Washington, USA.
J Virol. 2023 Nov 30;97(11):e0141423. doi: 10.1128/jvi.01414-23. Epub 2023 Nov 9.
The wide endemic range of mosquito-vectored flaviviruses-such as Zika virus and dengue virus serotypes 1-4-places hundreds of millions of people at risk of infection every year. Despite this, there are no widely available vaccines, and treatment of severe cases is limited to supportive care. An avenue toward development of more widely applicable vaccines and targeted therapies is the characterization of monoclonal antibodies that broadly neutralize all these viruses. Here, we measure how single amino acid mutations in viral envelope protein affect neutralizing antibodies with both broad and narrow specificities. We find that broadly neutralizing antibodies with potential as vaccine prototypes or biological therapeutics are quantifiably more difficult to escape than narrow, virus-specific neutralizing antibodies.
蚊媒黄病毒(如 Zika 病毒和登革热病毒血清型 1-4)广泛流行,每年使数亿人面临感染风险。尽管如此,目前还没有广泛可用的疫苗,严重病例的治疗也仅限于支持性护理。开发更广泛适用的疫苗和靶向疗法的一个途径是鉴定广泛中和所有这些病毒的单克隆抗体。在这里,我们测量了病毒包膜蛋白中的单个氨基酸突变如何影响具有广泛和狭窄特异性的中和抗体。我们发现,具有作为疫苗原型或生物治疗剂潜力的广泛中和抗体比狭窄的、病毒特异性的中和抗体更难逃避。