Superior immune responses from thermostable, single-administration rabies vaccines prepared using atomic layer deposition.

Shortcomings of current rabies virus (RABV) vaccines include thermal instability and the need for multiple injections to achieve protective immune responses. To overcome these drawbacks we describe a single-administration vaccine formulation prepared using a combination of spray-drying and atomic layer deposition (ALD) technologies. First, an inactivated RABV antigen is spray-dried from polysaccharide solutions to create glassy microparticles. ALD in a fluidized bed reactor is then used to deposit nanoscopic layers of alumina onto particle surfaces. The nanoscopic alumina coatings deposited by ALD provide a programmable delayed release of RABV antigen that enable both prime and boost vaccine functionality within a single injection. Immune responses to the resulting vaccines were tested following intramuscular administration in mice by measuring total anti-rabies IgG titers as well as neutralizing antibody titers. The immune responses to the spray-dried vaccines were unaffected by storage of the vaccines for 3 months at temperatures as high as 50 °C. ALD-coated rabies vaccine microparticles were also thermostable, with no changes in immunogenicity apparent after 3 months storage at 50 °C. Moreover, ALD-coated RABV vaccine microparticles induced IgG and neutralizing antibody titers nearly an order of magnitude higher than those generated in response to conventional liquid RABV vaccine formulations. Thus, spray-dried and ALD-coated RABV vaccine microparticle formulations offer both thermostability and superior immunogenicity from single vaccine administrations, with the potential for relaxed vaccine cold-chain requirements, antigen-sparing efficacy, and a reduced need for multiple administrations.