Mannosylated poly(beta-amino esters) for targeted antigen presenting cell immune modulation

Biomaterials. 2015 Jan;37:333-44. doi: 10.1016/j.biomaterials.2014.10.037. Epub 2014 Oct 22.

Abstract

Given the rise of antibiotic resistance and other difficult-to-treat diseases, genetic vaccination is a promising preventative approach that can be tailored and scaled according to the vector chosen for gene delivery. However, most vectors currently utilized rely on ubiquitous delivery mechanisms that ineffectively target important immune effectors such as antigen presenting cells (APCs). As such, APC targeting allows the option for tuning the direction (humoral vs cell-mediated) and strength of the resulting immune responses. In this work, we present the development and assessment of a library of mannosylated poly(beta-amino esters) (PBAEs) that represent a new class of easily synthesized APC-targeting cationic polymers. Polymeric characterization and assessment methodologies were designed to provide a more realistic physiochemical profile prior to in vivo evaluation. Gene delivery assessment in vitro showed significant improvement upon PBAE mannosylation and suggested that mannose-mediated uptake and processing influence the magnitude of gene delivery. Furthermore, mannosylated PBAEs demonstrated a strong, efficient, and safe in vivo humoral immune response without use of adjuvants when compared to genetic and protein control antigens. In summary, the gene delivery effectiveness provided by mannosylated PBAE vectors offers specificity and potency in directing APC activation and subsequent immune responses.

Keywords: Antigen presenting cells; Cationic polymers; Gene therapy; Nonviral vector; Vaccines.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen-Presenting Cells / immunology*
  • Female
  • Fluorescence
  • Green Fluorescent Proteins / metabolism
  • HeLa Cells
  • Humans
  • Immunization
  • Immunomodulation*
  • Mannose / chemistry*
  • Mice, Inbred BALB C
  • Models, Animal
  • Polymers / chemical synthesis
  • Polymers / chemistry*
  • Transfection

Substances

  • Polymers
  • enhanced green fluorescent protein
  • poly(beta-amino ester)
  • Green Fluorescent Proteins
  • Mannose