James R. Baker

NanoBio™ Nanoemulsion for Mucosal Vaccine Delivery

Nanoemulsions (NEs) are high-energy oil-in-water emulsions smaller than 1,000 nm that disrupt the outer lipid membrane of pathogenic microbes [1–4]. Building on studies that demonstrated the potential of NE to prevent influenza infection [5], it was recognized that NE inactivated influenza virus generated greater immune responses than formalin inactivated influenza virus when administered intranasally [6]. Subsequent studies have demonstrated this material acts as a mucosal adjuvant with numerous antigens including recombinant anthrax protective antigen (PA) [7], killed-vaccinia virus [8], recombinant human immunodeficiency (HIV) gp120 [9], recombinant hepatitis B surface antigen (HBsAg) [10], and purified Burkholderia cenocepacia outer membrane protein (OMP) [11]. In addition, it was recognized that the surfactant in the NE is locked at the interface between the oil droplets and water and does not appear to denature proteins. This confers thermostability to the antigen [10, 12–14] and potentially allows for the elimination of the cold chain required for all currently available vaccines [15]. The mechanisms by which adjuvants enhance the immune response are starting to be elucidated and include improved antigen delivery as well as innate immune activation [16]. The NE adjuvant acts via both mechanisms as it enhances antigen uptake by dendritic cells (DCs) as well as activating Toll like receptors (TLR) 2 and 4; this enhances both humoral and cell-mediated Th1 and Th17 immune responses [17]. Importantly, NE mucosal adjuvant activity occurs without damaging the mucosal epithelium [10] and has been demonstrated to be safe and well tolerated in early phase human clinical trials (Stanberry, submitted). In this review, we will delineate the physical and chemical properties, mechanisms of activity, preclinical studies, and clinical experience available regarding mucosal NE adjuvants.