Abstract

Nanoparticles are increasingly used to adjuvant vaccine formulations due to their biocompatibility, ease of manufacture and the opportunity to tailor their size, shape, and physicochemical properties. The efficacy of similarly-sized silica (Si-OH), poly (D,L-lactic-co-glycolic acid) (PLGA) and poly caprolactone (PCL) nanoparticles (nps) to adjuvant recombinant capsomere presenting antigenic M2e modular peptide from Influenza A virus (CapM2e) was investigated in vivo. Formulation of CapM2e with Si-OH or PLGA nps significantly boosted the immunogenicity of modular capsomeres, even though CapM2e was not actively attached to the nanoparticles prior to injection (i.e., formulation was by simple mixing). In contrast, PCL nps showed no significant adjuvant effect using this simple-mixing approach. The immune response induced by CapM2e alone or formulated with nps was antibody-biased with very high antigen-specific antibody titer and less than 20 cells per million splenocytes secreting interferon gamma. Modification of silica nanoparticle surface properties through amine functionalization and pegylation did not lead to significant changes in immune response. This study confirms that simple mixing-based formulation can lead to effective adjuvanting of antigenic protein, though with antibody titer dependent on nanoparticle physicochemical properties.

Highlights

  • Vaccination has proved to be one of the most influential developments in human health history

  • In the first study, adjuvanting efficacy of nanoparticles made of three different materials, biocompatible inorganic silica (Si-OH), biodegradable poly (PLGA) and polycaprolactone (PCL), were studied

  • The size of polyethylene glycol (PEG)-coated biodegradable nanoparticles could be controlled by varying the ratio of polymer to the oily emulsifier and by varying sonication conditions

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Summary

Introduction

Vaccination has proved to be one of the most influential developments in human health history. Vaccination has been based on live attenuated organisms, killed organisms or inactivated toxins. Vaccines based on these traditional approaches suffer from problems including reversion to their virulent state or limited duration of protection [1,2]. These limitations have led to shifting of interest towards recombinant proteins such as subunit vaccines, based on a specific portion of the pathogen. Subunit vaccines are being preferred over attenuated live or inactivated whole organism vaccines as they are generally well purified and characterized, have improved safety profile and are easier to scale up over the latter. Usually antigen by itself is weakly immunogenic, which necessitates use of an adjuvant in formulation [2]

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