Cortés Guadalupe, Ustyugova Irina, Farrell Timothy, McDaniel Clint, Britain Colleen, Romano Christopher, N'Diaye Siré, Zheng Lingyi, Ferdous Mithila, Iampietro Justin, Pougatcheva Svetlana, La Rue Lauren, Han Liqun, Ma Fuqin, Stegalkina Svetlana, Ray Satyajit, Zhang Jianxin, Barro Mario
Vaccines R&D, Sanofi, Cambridge, MA, USA.
Yoh Services LLC, Philadelphia, PA, USA.
NPJ Vaccines. 2024 Nov 19;9(1):228. doi: 10.1038/s41541-024-01011-x.
Neuraminidase (NA), the second most abundant surface glycoprotein on the influenza virus, plays a key role in viral replication and propagation. Despite growing evidence showing that NA-specific antibodies correlate with resistance to disease in humans, current licensed vaccines focus almost entirely on the hemagglutinin (HA) antigen. Here, we demonstrate that recombinant NA (rNA) protein is highly immunogenic in both naïve mice and ferrets, as well as in pre-immune ferrets, irrespective of the level of match with preexisting immunity. Ferrets vaccinated with rNA developed mild influenza disease symptoms upon challenge with human H3N2 influenza virus, and anti-NA antibody responses appeared correlated with reduction in disease severity. The addition of rNA to a quadrivalent HA-based vaccine induced robust NA-specific humoral immunity in ferrets, while retaining the ability to induce HA-specific immunity. These results demonstrate that the addition of rNA is a viable option to increase immunogenicity and potentially efficacy versus currently licensed influenza vaccines by means of boosting NA immunity.
神经氨酸酶（NA）是流感病毒表面第二丰富的糖蛋白，在病毒复制和传播中起关键作用。尽管越来越多的证据表明，NA特异性抗体与人类对疾病的抵抗力相关，但目前获批的疫苗几乎完全集中在血凝素（HA）抗原上。在此，我们证明重组NA（rNA）蛋白在未接触过抗原的小鼠和雪貂以及免疫前的雪貂中均具有高度免疫原性，与预先存在的免疫水平匹配程度无关。用rNA疫苗接种的雪貂在受到人类H3N2流感病毒攻击后出现轻度流感疾病症状，抗NA抗体反应似乎与疾病严重程度的降低相关。在基于HA的四价疫苗中添加rNA可在雪貂中诱导强大的NA特异性体液免疫，同时保留诱导HA特异性免疫的能力。这些结果表明，添加rNA是一种可行的选择，可通过增强NA免疫力来提高免疫原性，并可能提高与目前获批的流感疫苗相比的效力。
