Exploration of Encapsulation Methods of Subunit Vaccines

Background — Vaccination is one of the most effective tools for mitigating the impact of influenza epidemics and pandemics. However, commercially available flu vaccines are in general directed toward the specific strain(s) contained in the vaccine. Current flu vaccine strategies have two major drawbacks: lack of cross-protective immunity (i.e., the vaccine is not effective against multiple strains or types of flu) and lack of long-term effectiveness (i.e., the vaccine protection is short-lived and not potent enough.) Approach — To overcome the above issues, this project combines the expertise and strength of two research teams in the infectious disease field of Ohio State University (OSU) and SwRI. The team at OSU, led by Professor Renukaradhya J. Gourapura (DVM, PhD) and Dr. Chang Lee, focused on developing highly effective antigens that target the highly conserved region of swine influenza virus proteins found in multiple viral strains. The team at SwRI focused on developing an optimal delivery platform for the antigens. Specifically, SwRI used its knowledge in encapsulation to develop extended release nanoparticle vaccine formulations (using chitosan, polylactide-coglycolide-polyethylene glycol (PLGA-PEG) or lipids) with the goal of controlling release of the antigens while maintaining high loading efficiency and resulting in long-lasting immunity. To further increase the efficacy, SwRI included a novel adjuvant, monosodium urate crystals, developed through a SwRI project funded by the San Antonio Vaccine Development Center (SAVE). The nanoparticle formulations developed at SwRI were sent to OSU for testing for cross-protective immune response against influenza virus in the pig model. Accomplishments — Based on the hydrophobicity and isoelectric points of peptides and the matrix materials used they can either be encapsulated inside the core of the particles, or the core or lipid bilayer of liposomes. The use of chitosan resulted in no usable nanoparticles. Particles of both the PLGA-PEG and liposomal formulations containing the mixture of peptides and adjuvant were submitted for testing in the pig influenza model at OSU. The vaccine was intra-nasally administered to swine challenged with SIV (swine inflenza virus). Liposomal formulations showed positive results in the animal studies. We observed reduced gross lung lesion scores, interstitial pneumonia, H&E score, IL-10, IL-6, IFN-gamma levels in serum, lung lysate, and broncho alveolar lavage (BAL) fluid in liposomal formulation compared to nontreated control. In addition, the liposome vaccine formulation also illicits stronger IgA immune response instead of IgG immune response. This study demonstrates the promising efficacy of a liposomal flu subunit vaccine formulation.