title: Fabrication of nanoadjuvant with poly-ε-caprolactone (PCL) for developing a single-shot vaccine providing prolonged immunity.
abstract: OBJECTIVE
  The aim of the study was to load a model antigen, tetanus toxoid (TT), in poly-ε-caprolactone nanoparticles (PCL NPs) of two size ranges, ie, mean 61.2 nm (small) and 467.6 nm (large), and study its effect on macrophage polarization as well as antigen presentation in human monocyte-derived macrophages in vitro, along with humoral and cell-mediated immune (CMI) response generated in Swiss albino mice following immunization with the TT-loaded NPs.
  
  
  METHODS
  PCL NPs were synthesized by solvent evaporation. The antigen-loaded PCL NPs were characterized for size, zeta potential, and protein-release kinetics. Swiss albino mice were immunized with the antigen-loaded PCL NPs. Flow cytometry was used to quantify interferon-γ- and interleukin-4-secreting cluster of differentiation (CD)4(+) and CD8(+) T cells in the spleen, and enzyme-linked immunosorbent assay was used to quantify anti-TT antibody levels in the serum of immunized mice.
  
  
  RESULTS
  Small PCL NPs generated an M1/M2 type polarization of human blood monocyte-derived macrophages and T helper (Th)1/Th2 polarization of autologous CD4(+) T cells. Efficient CD8(+) T-cell responses were also elicited. Large PCL NPs failed to cause any type of macrophage polarization. They did not elicit efficient CD8(+) T-cell responses.
  
  
  CONCLUSIONS
  TT-loaded small PCL NPs were able to generate persistent and strong CMI and humoral responses against TT 2 months after single injection in mice without booster dose. This biodegradable nanoadjuvant system may help to develop single-shot immunization for prolonged immunity without booster doses. The capability of enhanced CMI response may have high translational potential for immunization against intracellular infection.
authors.affiliation: Department of Pathology, All India Institute of Medical Sciences, Jamia Hamdard, New Delhi, India.
authors.forename: Chandravilas Keshvan
authors.initials: CK
authors.lastname: Prashant
authors.affiliation: Department of Pathology, All India Institute of Medical Sciences, Jamia Hamdard, New Delhi, India.
authors.forename: Madhusudan
authors.initials: M
authors.lastname: Bhat
authors.affiliation: Department of Pathology, All India Institute of Medical Sciences, Jamia Hamdard, New Delhi, India.
authors.forename: Sandeep Kumar
authors.initials: SK
authors.lastname: Srivastava
authors.affiliation: Department of Transplant Immunology and Immunogenetics, All India Institute of Medical Sciences, Jamia Hamdard, New Delhi, India.
authors.forename: Ankit
authors.initials: A
authors.lastname: Saxena
authors.affiliation: Centre for Biomedical Engineering, Indian Institute of Technology, Jamia Hamdard, New Delhi, India.
authors.forename: Manoj
authors.initials: M
authors.lastname: Kumar
authors.affiliation: Department of Transplant Immunology and Immunogenetics, All India Institute of Medical Sciences, Jamia Hamdard, New Delhi, India.
authors.forename: Amar
authors.initials: A
authors.lastname: Singh
authors.affiliation: Department of Chemistry, Faculty of Sciences, Jamia Hamdard, New Delhi, India.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Samim
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, New Delhi, India.
authors.forename: Farhan Jalees
authors.initials: FJ
authors.lastname: Ahmad
authors.affiliation: Department of Pathology, All India Institute of Medical Sciences, Jamia Hamdard, New Delhi, India.
authors.forename: Amit Kumar
authors.initials: AK
authors.lastname: Dinda
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000737:chemistry*; D000818:Animals; D017951:Antigen Presentation; D002208:Caproates / Q000737:chemistry; D002460:Cell Line; D005260:Female; D006801:Humans; D007783:Lactones / Q000737:chemistry; D008264:Macrophages / Q000276:immunology; D051379:Mice; D050997:Nanomedicine; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry* / Q000648:ultrastructure; D036103:Nanotechnology; D010316:Particle Size; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013745:Tetanus Toxoid / Q000008:administration & dosage / Q000493:pharmacokinetics; D014612:Vaccines / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D000276:Adjuvants, Immunologic; D002208:Caproates; D007783:Lactones; D013745:Tetanus Toxoid; D014612:Vaccines; C121056:caprolactone
keywords: adjuvant; antigen cross-presentation; poly-ε-caprolactone nanoparticles; tetanus toxoid; vaccine