Saponin/lipid nanoparticles as an efficient adjuvant and delivery system for mucosal immunization

Background: Mucosal surfaces are one of the major entrances for infectious diseases and mucosal immune response serve as a first line of defense. For reasons of safety, efficacy and cost, mucosal administration of vaccines is... [ view full abstract ]

Background: Mucosal surfaces are one of the major entrances for infectious diseases and mucosal immune response serve as a first line of defense. For reasons of safety, efficacy and cost, mucosal administration of vaccines is today a one of priorities for immunizing against many infectious pathogens penetrating through mucosal gates. Most commercial vaccines today are injectable and use aluminum salts as their adjuvant component. These vaccines are unable to induce high levels of immune response when delivered at mucosal sites. In order to make them more immunogenic and prepare vaccine for mucosal immunization, strong mucosal adjuvants/delivery systems are required.
Recently purified triterpen saponins "GlabiloxTM" and "AsgipanTM" with low toxicity and high immunostimulatory activity were isolated from plants G. glabra and A. hippocastanum indigenous to Kazakhstan. Both saponins can interact with antigens and lipids resulting formation of nanoparticles 60-80 nm in size. Such nanoparticles can induce humoral and cellular immune responses through various routes of immunization, including intranasal, and provide protection against infection.
Methods: Influenza virus external glycoprotein antigens (HA+NA) were isolated from purified influenza virus by non-ionic detergent treatment. Triterpen saponins GlabiloxTM and AsgipanTM were isolated from plant tissues by ethanol extraction and purified by HPLC fractionation. Nanoparticles incorporated HA+NA antigens, lipids and saponins GlabiloxTM or AsgipanTM were prepared by dialysis technique. Humoral and cellular immune responses and protection against influenza infection were studied in animal vaccination/challenge experiments after single intranasal immunization of influenza subunit vaccine prepared on the base saponin/lipid nanoparticles.
Results: Intranasal immunization by subunit influenza vaccine on the base of nanoparticles contained HA+NA antigens, triterpen saponins GlabiloxTM or AsgipanTM and lipids stimulated formation of high levels of IgM, IgA, IgG1, IgG2a and IgG2b antibody and production of cytokines IL-2, IL-4, IL-10 and IFN-γ. Immunization/challenge experiments demonstrated 80-90% protection against influenza virus infection after single intranasal immunization of nanoparticulate influenza subunit vaccine in dose 5 µg per animal (Fig. 1).
Conclusion: Saponin/lipid nanoparticles contained influenza virus HA+NA antigens, lipids and saponins GlabiloxTM or AsgipanTM can be used as an efficient adjuvant/delivery system for mucosal (intranasal) immunization against influenza.