Abstract：
Human parainfluenza virus type 3 (hPIV3) is a respiratory pathogen that can cause severe disease in older people and infants. Currently, vaccines against hPIV3 are in clinical trials but none have been approved yet. The haemagglutinin-neuraminidase (HN) and fusion (F) surface glycoproteins of hPIV3 are major antigenic determinants. Here we describe naturally occurring potently neutralizing human antibodies directed against both surface glycoproteins of hPIV3. We isolated seven neutralizing HN-reactive antibodies and a pre-fusion conformation F-reactive antibody from human memory B cells. One HN-binding monoclonal antibody (mAb), designated PIV3-23, exhibited functional attributes including haemagglutination and neuraminidase inhibition. We also delineated the structural basis of neutralization for two HN and one F mAbs. MAbs that neutralized hPIV3 in vitro protected against infection and disease in vivo in a cotton rat model of hPIV3 infection, suggesting correlates of protection for hPIV3 and the potential clinical utility of these mAbs.
摘要：
人类副流感病毒3型（hPIV3）是一种呼吸道病原体，可在老年人和婴儿中引起严重疾病。目前,针对hPIV3的疫苗正在临床试验中，但尚未获得批准。hPIV3的血凝素-神经氨酸酶(HN)和融合(F)表面糖蛋白是主要的抗原决定簇。在这里，我们描述了天然存在的针对hPIV3两种表面糖蛋白的有效中和人抗体。我们从人记忆B细胞中分离出7种中和性HN反应性抗体和融合前构象F反应性抗体。一种结合HN的单克隆抗体（mAb），命名为PIV3-23,表现出包括血凝和神经氨酸酶抑制的功能属性。我们还描述了两种HN和一种FmAb的中和的结构基础。在hPIV3感染的棉鼠模型中，体外中和hPIV3的MAb在体内保护免受感染和疾病，提示hPIV3的保护和这些单克隆抗体的潜在临床效用的相关性。
