Screening amino acid additives as aerosolization modifiers for spray dried inhalable viral-vectored vaccines

Abstract

Adenoviral vectored vaccines are a promising platform for immunization against respiratory diseases. Despite the advantages offered by dry powder over parenteral administration, like thermal stability and possible immunization at the site of infection, aerosolization of such dry powders is challenging. In this study, eight amino acids were investigated to improve the aerosolization of spray-dried human adenovirus type 5 (AdHu5) in a mannitol/dextran matrix. All samples were characterized for relative yield from spray drying, particle size and morphology, thermal properties, residual moisture content, aerosol performance, and bioactivity of the encapsulated AdHu5. All particles were in the respirable size range (except glycine and tryptophan); however, most other amino acid-containing powders did not improve or detract from the aerosolization properties of the spray dried powders compared to the control binary blend comprised of mannitol/dextran only. All powders (except glycine) showed glass transition temperatures (Tg) considered adequate to retain thermal stability of the viral vectors in powder when stored at room temperatures. Among the samples screened, amino acid-containing samples showed reduced viral activity than control. To investigate the reduction in viral activity of AdHu5 upon addition of amino acids, further studies are required.