Abstract

Current vaccine research is mostly based on subunit antigens. Despite the better toxicity profile of these antigens they are often poorly immunogenic, so adjuvant association has been explored as a strategy to obtain a potent vaccine formulation. Recently, mast cell activators were recognized as a new class of vaccine adjuvants capable of potentiating mucosal and systemic immune responses. In this study, a co-adjuvanted delivery system was developed and characterized, combining the mast cell activator C48/80 with chitosan nanoparticles (Chi-C48/80 NPs), and the results were compared with plain chitosan nanoparticles. The adsorption of model antigens onto the NP surface as well as the biocompatibility of the system was not affected by the incorporation of C48/80 in the formulation. The stability of the nanoparticles was demonstrated by studying the variation of size and zeta potential at different times, and the ability to be internalized by antigen presenting cells was confirmed by confocal microscopy. Vaccination studies with hepatitis B surface antigen loaded Chi-C48/80 NPs validated the adjuvanticity of the delivery system, demonstrating for the first time a successful association between a mast cell activator and chitosan nanoparticles as a vaccine adjuvant for hepatitis B virus, applied to a nasal vaccination strategy.

Highlights

  • Traditional vaccines consisting of live attenuated or inactivated pathogens are highly immunogenic, but, due to safety concerns, development of new vaccines is being focused on the use of recombinant subunit antigens

  • We explore the feasibility of combining the mast cell activator with chitosan nanoparticles to prepare a new adjuvant formulation for nasal vaccination

  • Chitosan is a biomaterial with appealing properties for vaccine delivery

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Summary

Introduction

Traditional vaccines consisting of live attenuated or inactivated pathogens are highly immunogenic, but, due to safety concerns, development of new vaccines is being focused on the use of recombinant subunit antigens. Recombinant antigens are safer but they are often poorly immunogenic, requiring the use of adjuvants to enhance the resultant immune response. Different adjuvant approaches have been studied to enhance and/or modulate vaccine response to subunit antigens. Different nano-sized platforms such as virus-like particles, liposomes, immune stimulating complexes (ISCOMs), nanoemulsions, and polymeric nanoparticles have been explored as potential vaccine delivery systems [8,9]. Chitosan and its derivatives are among the most studied compounds for development of polymeric vaccines [10,11] because of their attractive characteristics for biomedical applications. Mucoadhesivity and immunostimulating properties [10] make it an attractive polymer, for the design of nanoparticulate vaccines for mucosal delivery

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