小柯机器人

美国国立卫生研究院John R. Mascola研究组的最新研究表明，接种稳定的呼吸道合胞病毒融合蛋白疫苗（RSV）可诱导遗传和抗原多样的抗体反应。相关论文在线发表在2021年4月5日出版的《免疫学》杂志上。

研究人员试图确定DS-Cav1疫苗接种是否诱导了可反映自然感染条件下产生的多样性抗体库，还是产生靶向特定表位的抗体谱系。研究人员使用互补B细胞测序的方法评估了六名参与者在疫苗接种前和接种后RSV F特异性B细胞应答，并鉴定了555个克隆谱系。DS-Cav1诱导的谱系识别F（pre-F）融合前的构象，并具有遗传多样性。其诱导产生的抗体可识别pre-F三聚体上所有六个抗原表位。

研究确定了34种共有克隆型，并且从主要克隆型对两种抗体的结构分析揭示了一种常见的识别模式。因此，用DS-Cav1进行疫苗接种可产生针对pre-F抗原表位的多样化多克隆反应，从而支持了针对pre-F的RSV疫苗开发和高级测试。

研究人员表示，尚未研发出有效的呼吸道合胞病毒疫苗。单剂量接种稳定的前糖蛋白（F）融合亚基疫苗（DS-Cav1）可大大提高健康成年人血清的中和活性。

附：英文原文

Title: Vaccination with prefusion-stabilized respiratory syncytial virus fusion protein induces genetically and antigenically diverse antibody responses

Author: Maryam Mukhamedova, Daniel Wrapp, Chen-Hsiang Shen, Morgan S.A. Gilman, Tracy J. Ruckwardt, Chaim A. Schramm, Larissa Ault, Lauren Chang, Alexandrine Derrien-Colemyn, Sarah A.M. Lucas, Amy Ransier, Samuel Darko, Emily Phung, Lingshu Wang, Yi Zhang, Scott A. Rush, Bharat Madan, Guillaume B.E. Stewart-Jones, Pamela J. Costner, LaSonji A. Holman, Somia P. Hickman, Nina M. Berkowitz, Nicole A. Doria-Rose, Kaitlyn M. Morabito, Brandon J. DeKosky, Martin R. Gaudinski, Grace L. Chen, Michelle C. Crank, John Misasi, Nancy J. Sullivan, Daniel C. Douek, Peter D. Kwong, Barney S. Graham, Jason S. McLellan, John R. Mascola

Issue&Volume: 2021-04-05

Abstract: An effective vaccine for respiratory syncytial virus (RSV) is an unrealized publichealth goal. A single dose of the prefusion-stabilized fusion (F) glycoprotein subunitvaccine (DS-Cav1) substantially increases serum-neutralizing activity in healthy adults.We sought to determine whether DS-Cav1 vaccination induces a repertoire mirroringthe pre-existing diversity from natural infection or whether antibody lineages targetingspecific epitopes predominate. We evaluated RSV F-specific B cell responses beforeand after vaccination in six participants using complementary B cell sequencing methodologiesand identified 555 clonal lineages. DS-Cav1-induced lineages recognized the prefusionconformation of F (pre-F) and were genetically diverse. Expressed antibodies recognizedall six antigenic sites on the pre-F trimer. We identified 34 public clonotypes, andstructural analysis of two antibodies from a predominant clonotype revealed a commonmode of recognition. Thus, vaccination with DS-Cav1 generates a diverse polyclonalresponse targeting the antigenic sites on pre-F, supporting the development and advancedtesting of pre-F-based vaccines against RSV.

DOI: 10.1016/j.immuni.2021.03.004

Source: https://www.cell.com/immunity/fulltext/S1074-7613(21)00116-3

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