Influenza Nanovaccines Containing Hemagglutinin Induce Humoral and Cell-Mediated Immunity

Acute respiratory infections are a significant concern throughout the world, contributing to 4.25 million deaths annually. One such pathogen, H5N1 avian influenza, has the potential to become the next pandemic threat. 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. However, because of the rapid mutation rate of RNA viruses like influenza, it is likely that human-to-human transmission is imminent, motivating the need for efficacious vaccines against pandemic influenzas.

Polyanhydride nanovaccines have been shown to be a versatile platform for the delivery of subunit vaccines. Nanoparticles composed of sebacic acid (SA), 1,6-bis-(p-carboxyphenoxy) hexane (CPH), and 1,8-bis-(p-carboxyphenoxy)-3,6-dioxaoctane (CPTEG), and their copolymers have been shown to sustain the release of encapsulated proteins while enhancing internalization by antigen presenting cells. Polyanhydride nanovaccines have also been shown to have immunomodulatory capabilities inducing both high avidity antibody titers as well as cell-mediated immune responses.

Previously, we have demonstrated that polyanhydride nanoparticles are capable of stably releasing recombinant H5 hemagglutinin, an antigen for H5N1 influenza. In this work, we characterized the in vivo immune responses generated by polyanhydride-based subunit nanovaccines. Polyanhydride nanovaccine formulations encapsulating rH5 were found to elicit high antigen-specific antibody titers as well as virus-neutralizing antibody titers. Likewise, enhanced T cell memory responses were observed at 63 days post immunization. Finally, the efficacy of a nanovaccine formulation was evaluated using a live viral challenge. All these studies together indicate that polyanhydride nanovaccines offer a patient-friendly and efficacious platform for next generation influenza A vaccines.