Development of a safe and effective novel synthetic mucosal adjuvant SF-10 derived from physiological metabolic pathways and function of human pulmonary surfactant

Abstract

A safe and effective mucosal adjuvant is required for vaccination against influenza A virus (IAV) infection. Previously, we described that intranasally administration of surfacten®, a medicine derived from bovine pulmonary surfactant (PS), with IAV vaccine can induce IAV-specific IgA in the respiratory tract mucosa and IgG in serum. PS is secreted by alveolar type II cells and Clara cells and serves to reduce lung surface tension. PS finished its rules is incorporated by antigen presenting cells (APCs), such as alveolar macrophages and dendritic cells, and alveolar type II cells and rapidly metabolized. We focused on the metabolic pathways and rapid metabolic turnover of PS and developed a PS-based mucosal adjuvant. First, we determined the essential components of PS adjuvanticity and found that the complex of three PS lipids and surfactant protein-C can enhance to deliver the vaccine antigen and activate APCs. Later, we improved the safety, efficacy and ease of manufacture and finally succeeded in developing SF-10. The use of SF-10 with influenza split vaccine (HAv) (HAv-SF-10) enhances HAv incorporation into APCs both in vitro and in vivo, and intranasal instillation of HAv-SF-10 induced systemic and mucosal HAv-specific immunities in not only mice but also cynomolgus monkeys. The report that PS has physiological effects on the gastrointestinal mucosa prompted us develop a new SF-10-based vaccine that can be administered orally. In this review, We summarize our work on the development of clinically effective PS-based nasal and oral mucosal adjuvants for influenza vaccine.

Keywords: Antigen delivery; Influenza vaccine; Mucosal adjuvant; Mucosal immunity; Pulmonary surfactant.