Evaluation of Immunogenicity and Safety of Polymer Based Nasal Vaccine

Background: Current Parenteral Hepatitis B vaccine induce only humoral immunity. Mucosal vaccination with polymer based delivery system via the nasal route would be ideal option to induce both mucosal and systemic immunity. Nasal route is having many advantages over parenteral route such as large surface area, easily accessible, Patient compliance and the disease is transmitted via the mucosal route. The most evaluated polymers for vaccine delivery are certainly poly (lactic-co-glycolic acid) (PLGA), poly (lactic acid) (PLA) and chitosan (derivatives). All these polymers are found to be safe, biodegradable and ideal to prepare particulate delivery systems.

Objectives: To prepare needle free delivery systems and that can induce both arms of systemic and mucosal immunity for HBsAg.

Methods: PLGA Nanoparticles (PLGA NP), PLGA-TMC Nanoparticles (PLGA-TMC NP) were prepared by double emulsion-Solvent extraction method and TMC NP by ionic complexation. The NP were characterized for surface morphology, size, charge, encapsulation efficiency, Invitro release and in vivo immunogenicity. Their toxicity was tested in vitro by stimulation of monocyte derived dendritic cells (DC). The immune responses were evaluated by measuring secretory IgA levels in mucosal fluids (nasal, vaginal) as well as cytokine levels in rat spleen homogenates. By using rat alveolar macrophages the particle uptake was studied.

Results: TMC NP and PLGA-TMC NP showed higher positive charge whereas PLGA NP carried a negative zeta potential. Immunogenicity increased as a function of particle size. All the NP was found to be safe. PLGA-TMC NP showed higher secretory antibody (IgA) as compared to PLGA and TMC NP.

Conclusions: Alum based vaccine can produce strong humoral immunity but less mucosal immunity whereas Polymer based delivery system can produce strong systemic and mucosal immunity. PLGA-TMC NP can be a better adjuvant or delivery system for nasal subunit vaccines.