甲型流感离子通道膜基质蛋白2（M2e）的胞外结构域被认为是开发通用甲型流感疫苗的潜在候选者。然而,M2e的低免疫原性存在显著的障碍。我们已经开发了包含与金纳米颗粒(AuNP)缀合的共有M2e肽和作为可溶性佐剂的CpG(AuNP-M2e+sCpG)的疫苗制剂。我们证明了AuNP-M2e+sCpG在小鼠中的鼻内递送诱导肺B细胞活化和稳健的血清抗M2e免疫球蛋白G(IgG)应答,同时刺激IgG1和IgG2a亚型。使用Madin-Darby犬肾（MDCK）细胞感染A/California/04/2009（H1N1pdm）大流行毒株，或A/Victoria/3/75(H3N2)，或高致病性禽流感病毒A/Vietnam/1203/2004（H5N1）作为免疫吸附剂，我们进一步表明，产生的抗体也能够与感染细胞上表达的M2的同四聚体形式结合。用A/California/04/2009（H1N1N1pdm）大流行毒株接种疫苗的小鼠的致命攻击，A/Victoria/3/75(H3N2),高致病性禽流感病毒A/越南/1203/2004（H5N1）导致100％，92%,100%保护,分别。总的来说,这项研究有助于奠定潜在的通用甲型流感疫苗的基础。
The extracellular domain of influenza A ion channel membrane matrix protein 2 (M2e) is considered to be a potential candidate to develop a universal influenza A vaccine. However poor immunogenicity of M2e presents a significant roadblock. We have developed a vaccine formulation comprising of the
consensus M2e peptide conjugated to gold nanoparticles (AuNPs) with CpG as a soluble adjuvant (AuNP-M2e + sCpG). We demonstrate that intranasal delivery of AuNP-M2e + sCpG in mice induces lung B cell activation and robust serum anti-M2e immunoglobulin G (IgG) response, with stimulation of both IgG1 and IgG2a subtypes. Using Madin-Darby canine kidney (MDCK) cells infected with A/California/04/2009 (H1N1pdm) pandemic strain, or A/Victoria/3/75 (H3N2), or the highly pathogenic avian influenza virus A/Vietnam/1203/2004 (H5N1) as immunosorbants we further show that the antibodies generated are also capable of binding to the homotetrameric form of M2 expressed on infected cells. Lethal challenge of vaccinated mice with A/California/04/2009 (H1N1pdm) pandemic strain, A/Victoria/3/75 (H3N2), and the highly pathogenic avian influenza virus A/Vietnam/1203/2004 (H5N1) led to 100%, 92%, and 100% protection, respectively. Overall, this study helps to lay the foundation of a potential universal influenza A vaccine.
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