Single low-dose un-adjuvanted HBsAg nanoparticle vaccine elicits robust, durable immunity – Corrected Proof – NanomedSpain

Single low-dose un-adjuvanted HBsAg nanoparticle vaccine elicits robust, durable immunity – Corrected Proof

Abstract: Chitosan nanoparticles were evaluated as a vaccine delivery system for hepatitis B surface antigen (HBsAg) in the absence of adjuvant. Nano-encapsulated HBsAg (HBsAg chitosan-NP) was endocytosed more rapidly and efficiently by dendritic cells compared to soluble HBsAg. FRET analysis demonstrated that intact nanoparticles were taken up by… Abstract: Chitosan nanoparticles were evaluated as a vaccine delivery system for hepatitis B surface antigen (HBsAg) in the absence of adjuvant. Nano-encapsulated HBsAg (HBsAg chitosan-NP) was endocytosed more rapidly and efficiently by dendritic cells compared to soluble HBsAg. FRET analysis demonstrated that intact nanoparticles were taken up by DCs. To determine the immunogenicity of adjuvant-free nano-encapsulated HBsAg, mice were immunized with a single dose of non-encapsulated HBsAg, HBsAg chitosan-NP, or HBsAg alum. Mice immunized with adjuvant-free nanoparticle elicited anti-HBs antibodies at significantly higher titers compared to mice immunized with HBsAg alum. Elevated numbers of BAFF-R+ B cells and CD138+ plasma cells account for the heightened anti-HBs response in nanoparticle immunized mice. Increases in Tfh cells provide a mechanism for the accumulation of anti-HBs secreting cells. Thus, chitosan nanoparticle vaccines represent a promising un-adjuvanted platform to generate robust and durable immunity to HBsAg and other subunit antigens following a single low-dose administration.Graphical Abstract: A novel hepatitis B vaccine consisting of adjuvant-free hepatitis B surface antigen (HBsAg) encapsulated within chitosan nanoparticles is more efficacious than the current licensed HBsAg alum vaccine. The nanoparticles are endocytosed rapidly by dendritic cells compared to non-encapsulated antigen. The activated dendritic cells stimulate robust adaptive immune responses, resulting in higher titers of serum anti-HBs antibodies compared to the HBsAg alum vaccine. The chitosan nanoparticles represent a promising vaccine delivery system as the elicitation of robust and durable immunity is achieved by a single low-dose administration of an adjuvant-free subunit antigen. (Graphical Abstract contains .)

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