Abstract：
The ectodomain of influenza matrix protein 2 (M2e) is a promising target for the development of universal prophylactic and therapeutic agents against influenza viruses of different subtypes. We constructed three M2e-specific monoclonal antibody variants, M2A1-1 (IgG1), M2A1-2a (IgG2a), M2A1-2b (IgG2b), which have the same Fab region targeting the M2e epitope but different isotypes, and compared their protective efficacy in influenza PR8-infected mice. We found that anti-M2e antibodies provided protection against influenza virus in a subtype-dependent manner, with the IgG2a variant providing significantly better protection with lower virus titers and milder lung injury than IgG1 and IgG2b isotypes. Additionally, we observed that the protective efficacy was dependent on the administration routes, with intranasal administration of antibody providing better protection than intraperitoneal administration. The timing of administration was also critical in determining the protective efficacy; while all the antibody isotypes provided protection when administered before influenza challenge, only IgG2a provided minimal protection when the antibodies were administered after virus challenge. These results provide valuable information for optimizing the therapeutics usage of M2e-based antibodies and furthering the development of M2e-based universal influenza vaccines.
摘要：
流感基质蛋白2（M2e）的胞外域是开发针对不同亚型流感病毒的通用预防和治疗剂的有希望的靶标。我们构建了三种M2e特异性单克隆抗体变体，M2A1-1(IgG1),M2A1-2a(IgG2a),M2A1-2b(IgG2b),它们具有相同的靶向M2e表位的Fab区，但同种型不同，并比较了它们在流感PR8感染小鼠中的保护功效。我们发现抗M2e抗体以亚型依赖性方式提供针对流感病毒的保护,与IgG1和IgG2b同种型相比，IgG2a变体提供了明显更好的保护，病毒滴度更低，肺损伤更轻。此外,我们观察到保护功效取决于给药途径，鼻内施用抗体比腹膜内施用提供更好的保护。给药时间在确定保护功效方面也很关键；虽然所有抗体同种型在流感攻击前给药时都提供保护，在病毒攻击后施用抗体时,只有IgG2a提供最小的保护.这些结果为优化基于M2e的抗体的治疗用途和进一步开发基于M2e的通用流感疫苗提供了有价值的信息。
