Nano/microparticle Formulations for Universal Influenza Vaccines

AAPS J. 2022 Jan 7;24(1):24. doi: 10.1208/s12248-021-00676-9.


Influenza affects millions of people worldwide and can result in severe sickness and even death. The best method of prevention is vaccination; however, the seasonal influenza vaccine often suffers from low efficacy and requires yearly vaccination due to changes in strain and viral mutations. More conserved universal influenza antigens like M2 ectodomain (M2e) and the stalk region of hemagglutinin (HA stalk) have been used clinically but often suffer from low antigenicity. To increase antigenicity, universal antigens have been formulated using nano/microparticles as vaccine carriers against influenza. Utilizing polymers, liposomes, metal, and protein-based particles, indicators of immunity and protection in mouse, pig, ferrets, and chicken models of influenza have been shown. In this review, seasonal and universal influenza vaccine formulations comprised of these materials including their physiochemical properties, fabrication, characterization, and biologic responses in vivo are highlighted. The review is concluded with future perspectives for nano/microparticles as carrier systems and other considerations within the universal influenza vaccine delivery landscape. Graphical Abstract.

Keywords: flu; gold nanoparticles; liposomes; polymeric nanoparticles; protein nanoparticles.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Antigens, Viral / immunology
  • Chemistry, Pharmaceutical / methods
  • Disease Models, Animal
  • Drug Delivery Systems*
  • Humans
  • Influenza Vaccines / administration & dosage*
  • Influenza Vaccines / immunology
  • Influenza, Human / immunology
  • Influenza, Human / prevention & control*
  • Influenza, Human / virology
  • Microspheres
  • Nanoparticles
  • Orthomyxoviridae / immunology
  • Orthomyxoviridae / isolation & purification
  • Vaccination / methods


  • Antigens, Viral
  • Influenza Vaccines