Department of Microbiology, Icahn School of Medicine at Mount Sinaigrid.59734.3c, New York, New York, USA.
Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinaigrid.59734.3c, New York, New York, USA.
J Virol. 2022 Jan 26;96(2):e0142121. doi: 10.1128/JVI.01421-21. Epub 2021 Oct 20.
The public health burden caused by influenza virus infections is not adequately addressed with existing vaccines and antivirals. Identifying approaches that interfere with human-to-human transmission of influenza viruses remains a pressing need. The importance of neuraminidase (NA) activity for the replication and spread of influenza viruses led us to investigate whether broadly reactive human anti-NA monoclonal antibodies (MAbs) could affect airborne transmission of the virus using the guinea pig model. In that model, infection with recent influenza virus clinical isolates resulted in 100% transmission from inoculated donors to recipients in an airborne transmission setting. Anti-NA MAbs were administered either to the inoculated animals on days 1, 2, and 4 after infection or to the naive contacts on days 2 and 4 after donor infection. Administration of NA-1G01, a broadly cross-reactive anti-NA MAb, to either the donor or recipient reduced transmission of the A/New York City/PV02669/2019 (H1N1) and A/New York City/PV01148/2018 (H3N2) viruses. Administration of 1000-3C05, an anti-N1 MAb, to either the donor or recipient reduced transmission of A/New York City/PV02669/2019 (H1N1) virus but did not reduce transmission of A/New York City/PV01148 (H3N2) virus. Conversely, 229-2C06, an anti-N2 MAb, reduced transmission of A/New York City/PV01148 (H3N2) but did not impact transmission of A/New York City/PV02669/2019 (H1N1) virus. Our work demonstrates that anti-NA MAbs could be further developed into prophylactic or therapeutic agents to prevent influenza virus transmission to control viral spread. The burden of influenza remains substantial despite unremitting efforts to reduce the magnitude of seasonal influenza epidemics and prepare for pandemics. Although vaccination remains the mainstay of these efforts, current vaccines are designed to stimulate an immune response against the viral hemagglutinin. Interest in the role immunity against neuraminidase plays in influenza virus infection and transmission has recently surged. Human antibodies that bind broadly to neuraminidases of diverse influenza viruses and protect mice against lethal viral challenge have previously been characterized. Here, we show that three such antibodies inhibit the neuraminidase activity of recent isolates and reduce their airborne transmission in a guinea pig model. In addition to contributing to the accumulating support for incorporating neuraminidase as a vaccine antigen, these findings also demonstrate the potential of direct administration of anti-neuraminidase antibodies to individuals infected with influenza virus and to individuals for postexposure prophylaxis to prevent the spread of influenza virus.
流感病毒感染造成的公共卫生负担尚未得到现有疫苗和抗病毒药物的充分解决。寻找能够干预流感病毒人际传播的方法仍然是当务之急。神经氨酸酶（NA）活性对于流感病毒的复制和传播至关重要，这促使我们利用豚鼠模型研究是否可以使用广泛反应性的人抗 NA 单克隆抗体（MAb）来影响病毒的空气传播。在该模型中，最近的流感病毒临床分离株感染导致接种供体的病毒在空气传播环境中 100%传播给受体。在感染后第 1、2 和 4 天，将抗 NA MAb 分别施用于接种的动物，或在供体感染后第 2 和 4 天，将抗 NA MAb 施用于未感染的接触者。向供体或受体施用广泛交叉反应的抗 NA MAb NA-1G01 可降低 A/New York City/PV02669/2019（H1N1）和 A/New York City/PV01148/2018（H3N2）病毒的传播。向供体或受体施用抗 N1 MAb 1000-3C05 可降低 A/New York City/PV02669/2019（H1N1）病毒的传播，但不能降低 A/New York City/PV01148（H3N2）病毒的传播。相反，抗 N2 MAb 229-2C06 降低了 A/New York City/PV01148（H3N2）病毒的传播，但对 A/New York City/PV02669/2019（H1N1）病毒的传播没有影响。我们的工作表明，抗 NA MAb 可以进一步开发为预防或治疗剂，以防止流感病毒传播，从而控制病毒传播。尽管为减轻季节性流感流行的严重程度和为大流行做好准备做出了不懈努力，但流感的负担仍然很大。尽管疫苗接种仍然是这些努力的主要手段，但目前的疫苗旨在刺激针对病毒血凝素的免疫反应。人们对针对神经氨酸酶的免疫在流感病毒感染和传播中的作用的兴趣最近急剧增加。以前已经鉴定出与人流感病毒的神经氨酸酶广泛结合并保护小鼠免受致命病毒攻击的人抗体。在这里，我们表明，这三种抗体抑制了最近分离株的神经氨酸酶活性，并在豚鼠模型中降低了它们的空气传播。除了为将神经氨酸酶作为疫苗抗原纳入提供了更多支持外，这些发现还表明，直接向感染流感病毒的个体以及用于暴露后预防的个体施用抗神经氨酸酶抗体，有可能防止流感病毒的传播。
