Journal
MOLECULAR PHARMACEUTICS
Volume 13, Issue 2, Pages 472-482Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.molpharmaceut.5b00707
Keywords
chitosan nanoparticles; gene delivery; DNA vaccine; nasal immunization; hepatitis B vaccine
Funding
- FEDER funds through the Operational Programme Competitiveness Factors - COMPETE
- national funds by FCT - Foundation for Science and Technology [PTDC/SAU-FAR/115044/2009]
- GlaxoSmithKline
- FCT fellowships [SFRH/BD/64046/2009]
- [UID/NEU/04539/2013]
- Fundação para a Ciência e a Tecnologia [SFRH/BD/64046/2009, PTDC/SAU-FAR/115044/2009] Funding Source: FCT
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The generation of strong pathogen-specific immune responses at mucosal surfaces where hepatitis B virus (HBV) transmission can occur is still a major challenge. Therefore, new vaccines are urgently needed in order to overcome the limitations of existing parenteral ones. Recent studies show that this may be achieved by intranasal immunization. Chitosan has gained attention as a nonviral gene delivery system; however, its use in vivo is limited due to low transfection efficiency mostly related to strong interaction between the negatively charged DNA and the positively charged chitosan. We hypothesize that the adsorption of negatively charged human serum albumin (HSA) onto the surface of the chitosan particles would facilitate the intracellular release of DNA, enhancing transfection activity. Here, we demonstrate that a robust systemic immune response was induced after vaccination using HSA-loaded chitosan nanoparticle/DNA (HSA-CH NP/DNA) complexes. Furthermore, intranasal immunization with HSA-CH NP/DNA complexes induced HBV specific IgA in nasal and vaginal secretions; no systemic or mucosal responses were detected after immunization with DNA alone. Overall, our results show that chitosan-based DNA complexes elicited both humoral and mucosal immune response, making them an interesting and valuable gene delivery system for nasal vaccination against HBV.
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