Pharmaceutics, Preformulation and Drug Delivery
Enhanced Immune Response Against Pertussis Toxoid by IgA-Loaded Chitosan–Dextran Sulfate Nanoparticles

https://doi.org/10.1002/jps.22763Get rights and content

ABSTRACT:

The objective of the present study was to evaluate immunological activities of chitosan–dextran sulfate (CS–DS) nanoparticle formulation of pertussis toxoid (PTXd) and its combination with a potential immunological adjuvant, immunoglobulin A (IgA). CS–DS nanoparticles were prepared using a complex coacervation (polyelectrolyte complexation) technique. CS–DS nanoparticle formulations with size and zeta potential in a range of 300–350 nm and +40–+55 mV, respectively, were obtained. An entrapment efficiency of more than 90% was obtained for pertussis toxin and IgA in CS–DS nanoparticles. All loaded nanoparticle formulations showed less than 20% of release within 24 h in in vitro release studies. The immunological evaluation of developed formulations in female Balb/c mice groups showed that the CS–DS nanoparticles formulations induced significantly higher serum IgG and IgG1 titers (p < 0.05) as compared with conventional alum-adjuvanted PTXd formulation administered by subcutaneous route. This study indicated the potential of CS–DS nanoparticles to be a simple and effective particulate delivery system with in-built immunological adjuvant property for acellular protein antigens. The study also revealed the potential important role of IgA-loaded CS–DS nanoparticles as a novel immunological adjuvant for vaccine delivery. © 2011 Wiley Periodicals, Inc. and the American Pharmacists Association.

Section snippets

INTRODUCTION

The emerging trend in new vaccine development is to identify potentially protective antigens/antigenic determinants and develop recombinant or synthetic peptide-based or conjugate vaccines. This approach can offer a better immunogenicity/risk ratio and avoid the use of inactivated or attenuated whole-cell vaccines and associated regulatory hurdles. However, in many instances, purified and synthetic antigens are poorly immunogenic and thus require delivery systems that are capable of improving

Materials

Mouse IgA-kappa from murine melanoma, 3,3′,5,5′-tetramethylbenzidine-2 (TMB-2) liquid substrate system, tris-buffered saline powder, phosphate buffered saline (PBS), glutaraldehyde grade I (8% in water), Tween-20, bovine serum albumin (BSA), l-lysine, CS [low molecular weight (MW) ∼150,000; 75%–85% deacetylated], DS sodium salt (MW ∼5000), and carbonate–bicarbonate buffer capsules were purchased from Sigma–Aldrich Pty Ltd. (Sydney, New South Wales, Australia). Ham's F-12 nutrient mixture, fetal

RESULTS AND DISCUSSION

The incidence of B. pertussis infections such as whooping cough has been significantly reduced by the introduction of pertussis vaccines and immunization programs. Although whole-cell pertussis vaccines have been used for many decades and are still commonly used in the developing world, the more recent development and introduction of acellular pertussis vaccines has both increased the compliance with vaccination programs and reduced the severity of adverse reactions to the vaccine.25,26 PTX is

CONCLUSIONS

To summarize, the in vivo studies conducted in this investigation indicate that the CS–DS nanoparticulate delivery system can be useful in the delivery of vaccines through the SC route, as this system significantly enhances Th2-type immune responses against the antigen. In addition, IgA incorporation in combination with the antigen in the CS–DS nanoparticles may further enhance the induction of humoral immune response. The ability of the CS–DS nanoparticles to co-incorporate the protein antigen

Acknowledgements

Sameer Sharma is thankful to the Department of Education, Employment and Workplace Relations and School of Pharmacy, Curtin University, for providing a Ph.D. scholarship. Authors acknowledge Dr. Simon Fox and Ms. Erin Bolitho for assistance with the cell-culture work. This project was partially supported by a Curtin University Internal Research Grant.

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