Evaluation of the usefulness of hydroxypropyl cellulose and sucrose in the nasal influenza vaccine

Abstract

The preventative efficacy of the influenza vaccine could be induced by the administration on the surface of the nasal mucosa, thereby enabling secretory IgA antibody production on the mucosal surface. For effective induction of the mucosal immune response, the vaccines have to reach the nasopharyngeal lymphoid tissue located in the deep part of the nasal cavity. To achieve this, vaccines should be formulated in powder form, in order to preserve the antigen physicochemical characteristics. Although proteins are generally stable in the powder form in the presence of amorphous sucrose, this amorphous sugar is particularly hygroscopic, undergoing facile deliquescence, and becoming unsuitable for intranasal administration. In this study, it was demonstrated that a stable powder could be manufactured by co-spray-drying hydroxypropyl cellulose and sucrose. The influenza antigen was then formulated with these excipients as a powdered pharmaceutical product, and the activity of the antigen was confirmed following long-term storage. In addition, following long-term storage, the powder was nasally administered to mice to evaluate its immunogenicity, and it was confirmed that secretory IgA production was induced on the mucosal surface. Thus, using sucrose and hydroxypropyl cellulose as excipients for a nasal influenza powder vaccine, a technology was established to stabilize the powdered influenza antigen.