title: Carbohydrate-functionalized nanovaccines preserve HIV-1 antigen stability and activate antigen presenting cells.
abstract: The functionalization of polymeric nanoparticles with ligands that target specific receptors on immune cells offers the opportunity to tailor adjuvant properties by conferring pathogen mimicking attributes to the particles. Polyanhydride nanoparticles are promising vaccine adjuvants with desirable characteristics such as immunomodulation, sustained antigen release, activation of antigen presenting cells (APCs), and stabilization of protein antigens. These capabilities can be exploited to design nanovaccines against viral pathogens, such as HIV-1, due to the important role of dendritic cells (DCs) and macrophages in viral spread. In this work, an optimized process was developed for carbohydrate functionalization of HIV-1 antigen-loaded polyanhydride nanoparticles. The carbohydrate-functionalized nanoparticles preserved antigenic properties upon release and also enabled sustained antigen release kinetics. Particle internalization was observed to be chemistry-dependent with positively charged nanoparticles being taken up more efficiently by DCs. Up-regulation of the activation makers CD40 and CD206 was demonstrated with carboxymethyl-α-d-mannopyranosyl-(1,2)-d-mannopyranoside functionalized nanoparticles. The secretion of the cytokines IL-6 and TNF-α was shown to be chemistry-dependent upon stimulation with carbohydrate-functionalized nanoparticles. These results offer important new insights upon the interactions between carbohydrate-functionalized nanoparticles and APCs and provide foundational information for the rational design of targeted nanovaccines against HIV-1.
authors: a Department of Chemical and Biological Engineering , Iowa State University , Ames , IA 50011 , USA.
authors: J E
authors: JE
authors: Vela Ramirez
authors: R
authors: R
authors: Roychoudhury
authors: H H
authors: HH
authors: Habte
authors: M W
authors: MW
authors: Cho
authors: N L B
authors: NL
authors: Pohl
authors: B
authors: B
authors: Narasimhan
mesh_terms: D016915:AIDS Vaccines / Q000737:chemistry / Q000276:immunology*; D000276:Adjuvants, Immunologic; D000818:Animals; D019013:CD40 Antigens / Q000378:metabolism; D002241:Carbohydrates / Q000737:chemistry*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D015700:HIV Envelope Protein gp41 / Q000737:chemistry / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D015850:Interleukin-6 / Q000378:metabolism; D037181:Lectins, C-Type / Q000378:metabolism; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000378:metabolism; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000737:chemistry*; D049388:Polyanhydrides / Q000737:chemistry; D011956:Receptors, Cell Surface / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014614:Vaccines, Synthetic
chemical_list: D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D019013:CD40 Antigens; D002241:Carbohydrates; D015700:HIV Envelope Protein gp41; D015850:Interleukin-6; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D049388:Polyanhydrides; D011956:Receptors, Cell Surface; D014409:Tumor Necrosis Factor-alpha; D014614:Vaccines, Synthetic; C577686:interleukin-6, mouse
keywords: HIV antigen; carbohydrates; dendritic cells; nanoparticles; nanovaccines; polyanhydrides; targeting