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Protective Antibodies Against Human Parainfluenza Virus Type 3 (HPIV3) Infection
bioRxiv - Immunology Pub Date : 2020-10-30 , DOI: 10.1101/2020.06.15.153478
Jim Boonyaratanakornkit , Suruchi Singh , Connor Weidle , Justas Rodarte , Ramasamy Bakthavatsalam , Jonathan Perkins , Guillaume B.E. Stewart-Jones , Peter D. Kwong , Andrew T. McGuire , Marie Pancera , Justin J. Taylor

Human parainfluenza virus type III (HPIV3) is a common respiratory pathogen that afflicts children and can be fatal in vulnerable populations, including the immunocompromised. Unfortunately, an effective vaccine or therapeutic is not currently available, resulting in tens of thousands of hospitalizations per year. In an effort to discover a protective antibody against HPIV3, we screened the B cell repertoires from peripheral blood, tonsils, or spleen from healthy children and adults. These analyses yielded five monoclonal antibodies that potently neutralized HPIV3 in vitro. These HPIV3 neutralizing antibodies targeted two non-overlapping epitopes of the HPIV3 F protein, with most targeting the apex. Importantly, prophylactic administration of one of these antibodies, named PI3-E12, resulted in potent protection against HPIV3 infection in cotton rats. Additionally, PI3-E12 could also be used therapeutically to suppress HPIV3 in immunocompromised animals. These results demonstrate the potential clinical utility of PI3-E12 for the prevention or treatment of HPIV3 in both immunocompetent and immunocompromised individuals.

中文翻译:

抗人副流感病毒3型(HPIV3)感染的保护性抗体

III型人类副流感病毒(HPIV3)是困扰儿童的常见呼吸道病原体,在弱势人群中可能致命,包括免疫功能低下。不幸的是,目前没有有效的疫苗或治疗剂,导致每年数以万计的住院治疗。为了发现针对HPIV3的保护性抗体,我们从健康儿童和成人的外周血,扁桃体或脾脏中筛选了B细胞库。这些分析产生了五种在体外有效中和HPIV3的单克隆抗体。这些HPIV3中和抗体靶向HPIV3 F蛋白的两个非重叠表位,大多数靶向顶点。重要的是,预防性施用这些抗体之一,称为PI3-E12,可以有效抵抗棉花大鼠中的HPIV3感染。另外,PI3-E12还可以在治疗上用于抑制免疫受损动物中的HPIV3。这些结果证明了PI3-E12在预防或治疗免疫能力强和免疫功能低下的个体中对HPIV3的潜在临床实用性。
更新日期:2020-11-02
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