Abstract
Developing influenza vaccines that protect against a broad range of viruses is a global health priority. Several conserved viral proteins or domains have been identified as promising targets for such vaccine development. However, none of the targets is sufficiently immunogenic to elicit complete protection, and vaccine platforms that can enhance immunogenicity and deliver multiple antigens are desperately needed. Here, we report proof-of-concept studies for the development of next-generation influenza vaccines using the bacteriophage T4 virus-like particle (VLP) platform. Using the extracellular domain of influenza matrix protein 2 (M2e) as a readout, we demonstrate that up to ~1,281 M2e molecules can be assembled on a 120 x 86 nanometer phage capsid to generate M2e-T4 VLPs. These M2e-decorated nanoparticles, without any adjuvant, are highly immunogenic, stimulate robust humoral as well as cellular immune responses, and conferred complete protection against lethal influenza virus challenge. Potentially, additional conserved antigens could be incorporated into the M2e-T4 VLPs and mass-produced in E. coli in a short amount of time to deal with an emerging influenza pandemic.
Highlights
Influenza A (Flu) virus is a highly contagious infectious agent that can cause severe respiratory disease [1, 2]
Since M2e-induced immune protection mainly depends on antibody-dependent cellular cytotoxicity (ADCC) and antibodydependent cellular phagocytosis (ADCP), we examined whether M2e presented in plasma membranes of influenza virus-infected cells can be recognized by 3M2e-T4 induced antibodies
The influenza virus M2e antigen is considered to be an attractive target for the development of universal influenza vaccines
Summary
Influenza A (Flu) virus is a highly contagious infectious agent that can cause severe respiratory disease [1, 2]. Engineered headless HA stalk, in which the immunodominant head domain was removed, was mainly used to induce antibodies that recognize or neutralize diverse influenza virus strains [18, 19]. Another widely used target for universal Flu vaccines is the extracellular domain of matrix protein 2 (M2e) that is highly conserved among divergent influenza virus strains [14, 20, 21]. None of these vaccine targets are highly immunogenic and many strategies were employed to enhance their immunogenicity [22,23,24,25]
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