Annually recurring seasonal influenza causes massive economic loss and poses severe threats to public health worldwide. The current seasonal influenza vaccines are the most effective means of preventing influenza infections but possess major weaknesses. Seasonal influenza vaccines require annual updating of the vaccine strains. However, it is an unreachable task to accurately predict the future circulating strains. Vaccines with mismatched strains dramatically compromise the vaccine efficacy. In addition, the seasonal influenza vaccines are ineffective against an unpredictable pandemic. A universal influenza vaccine would overcome these weaknesses of the seasonal vaccines and abolish the threat of influenza pandemics. One approach under investigation is to design influenza vaccine immunogens based on conserved, type-specific amino acid sequences and conformational epitopes, rather than strain-specific. Such vaccines can elicit broadly reactive humoral and cellular immunity. Universal influenza vaccine development has intensively employed nanotechnology because the structural and morphological properties of nanoparticles dramatically improve vaccine immunogenicity and the induced immunity duration. Layered protein nanoparticles can decrease off-target immune responses, fine-tune antigen recognition and processing, and facilitate comprehensive immune response induction. Herein, we review the designs of effective nanoparticle universal influenza vaccines, the recent discoveries of specific nanoparticle features that contribute to immunogenicity enhancement, and recent progress in clinical trials.
Keywords: headless hemagglutinin; long-lasting; matrix protein 2; prophylaxis; self-assembling; virus-like particle.