Nanoadjuvants for Effective Vaccines Against Influenza A Virus

The 2009 H1N1 influenza virus, or swine flu, resulted in a global pandemic and caused the deaths of approximately 280,000 patients. This strain of H1N1 influenza, a combination of a triple reassortant (avian, swine, and human) and Eurasian swine influenza virus, was readily transmitted via infected respiratory droplets and rapidly spread among populations world-wide. In addition, H5N1 avian influenza has the potential to become one of the next pandemic threats. While currently not transmitted human-to-human, recent cases of H5N1 have been shown to result in a 60% fatality rate and an increasing resistance to antiviral treatments. Aside from typical influenza symptoms of fever, cough, and sinus issues, many pandemic influenza patients developed severe respiratory distress or further complications of secondary bacterial infections. Thus, new vaccine technologies are needed to prevent and control pandemic influenza.

Subunit vaccines are a recent, alternative technology for the prevention of influenza. However, due to the poor immunogenicity of subunit proteins, novel adjuvants must be used to enhance efficacy. Polyanhydride nanoparticles have previously been demonstrated to improve stability and control the release of subunit proteins. In addition, polyanhydride nanoparticles have been shown to increase uptake of antigen by antigen presenting cells, resulting in enhanced antibody titers and cell-mediated immune responses.

Our recent work has suggested that the combination of adjuvants and delivery platforms may be beneficial in stimulating different immune pathways. In this work, polyanhydride nanoparticles were combined with a novel, pentablock copolymer hydrogel for the delivery of H5N1 and H1N1 subunit vaccines. Mice were subcutaneously administered the combined adjuvant platform encapsulating H5N1 hemagglutinin and it was shown that the combination nanovaccine platform performed better than the two individual nanovaccines in terms of recovery of body weight and virus load in the lungs after challenge. In addition, we studied the efficacy of the nanovaccine by formulating H1N1 hemagglutinin and nucleoprotein into polyanhydride nanoparticles. Finally, the efficacy of the nanovaccine was determined using a live, viral challenge.