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.

3 型人类副流感病毒 (hPIV3) 是一种呼吸道病原体，可导致老年人和婴儿患严重疾病。目前，针对 hPIV3 的疫苗正在进行临床试验，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 两种表面糖蛋白的强中和人类抗体。我们从人记忆 B 细胞中分离出 7 种中和 HN 反应性抗体和一种融合前构象 F 反应性抗体。一种 HN 结合单克隆抗体 (mAb)，命名为 PIV3-23，表现出包括血凝和神经氨酸酶抑制在内的功能特性。我们还描述了两种 HN 和一种 F mAb 的中和结构基础。在 hPIV3 感染的棉鼠模型中，体外中和 hPIV3 的单克隆抗体可防止体内感染和疾病，这表明对 hPIV3 的保护与这些单克隆抗体的潜在临床用途之间存在相关性。