Journal
MOLECULAR PHARMACEUTICS
Volume 15, Issue 1, Pages 72-82Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.molpharmaceut.7b00730
Keywords
nanoparticles; immunological adjuvant; poly-epsilon-caprolactone; chitosan; HBsAg; CpG-ODN
Funding
- FEDER funds through the Operational Programme Competitiveness Factors-COMPETE
- FCT-Foundation for Science and Technology [PTDC/SAU-FAR/115044/2009, DFRH-SFRH/BD/81350/2011, POCI-01-0145-FEDER-007440 (UID/NEU/04539/2013)]
- FCT [REDE/1510/RME/2005]
- Fundação para a Ciência e a Tecnologia [PTDC/SAU-FAR/115044/2009] Funding Source: FCT
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Polymeric nanoparticles (NPs) are extremely attractive vaccine adjuvants, able to promote antigen delivery and in some instances, exert intrinsic immunostimulatory properties that enhance antigen specific humoral and cellular immune responses. The poly-e-caprolactone (PCL)/chitosan NPs were designed with the aim of being able to combine the properties of the 2 polymers in the preparation of an adjuvant for the hepatitis B surface antigen (HBsAg). This article reports important results of an in vitro mechanistic study and immunization studies with HBsAg associated with different concentrations of the nanoparticles. The results revealed that PCL/chitosan NPs promoted mast cell (MC) activation (beta-hexosaminidase release) and that its adjuvant effect is not mediated by the TNF-alpha secretion. Moreover, we demonstrated that HBsAg loaded PCL/chitosan NPs, administered through the subcutaneous (SC) route, were able to induce higher specific antibody titers without increasing IgE when compared to a commercial vaccine, and that the IgG titers are nanoparticle-dose dependent. The results also revealed the NPs' capability to promote a cellular immune response against HBsAg, characterized by the production of IFN-gamma and IL-17. These results demonstrated that PCL/chitosan NPs are a good hepatitis B antigen adjuvant, with direct influence on the intensity and type of the immune response generated.
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