title: Topical Administration Is a Promising Inoculating Route versus Intramuscular Inoculation for the Nanoparticle-Carried DNA Vaccine to Prevent Corneal Infections.
abstract: OBJECTIVE
  To evaluate the comparative effect of topical versus intramuscular administration of nanoparticle-carried DNA vaccine in preventing corneal herpes simplex virus type 1 (HSV-1) infection.
  
  
  METHODS
  Nanoparticle [polyethylenimine (PEI)-Fe3O4]-carried DNA vaccine (PEI-Fe3O4-pRSC-gD-IL-21) or DNA vaccine (pRSC-gD-IL-21) alone were topically versus intramuscularly inoculated into one eye each of mice on days 0, 14 and 28. Three weeks after the final immunization, the specific immune responses and clinical degrees of primary herpes simplex keratitis were evaluated.
  
  
  RESULTS
  Topical inoculation of nanoparticle-carried DNA vaccine induced mice to generate similar levels of specific HSV-1-neutralizing antibody, IFN-γ and IL-4 in serum and specific killing (cytotoxicity) and proliferative activities of the splenic lymphocytes, but a significantly higher level of secretory IgA in tears compared to those of intramuscular inoculation. More importantly, the mice inoculated topically showed a significantly decreased herpes simplex keratitis severity than the mice inoculated intramuscularly after HSV-1 challenge on the corneas of the mice.
  
  
  CONCLUSIONS
  Topical inoculation of nanoparticle-carried DNA vaccine elicits a stronger specific local immune response and more effectively inhibits herpes simplex keratitis as compared to intramuscular inoculation in an HSV-1 ocular challenge mouse model. Thus, topical administration may be a promising inoculating route for the nanoparticle-carried DNA vaccine to prevent corneal infections.
authors.affiliation: Department of Ophthalmology, Zhong Da Hospital, Southeast University, Nanjing, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Hu
authors.forename: Tejsu
authors.initials: T
authors.lastname: Malla
authors.forename: Yujia
authors.initials: Y
authors.lastname: Zhai
authors.forename: Lili
authors.initials: L
authors.lastname: Dong
authors.forename: Ru
authors.initials: R
authors.lastname: Tang
mesh_terms: D000287:Administration, Topical; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D004337:Drug Carriers; D019084:Fluorescent Antibody Technique, Indirect; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000276:immunology; D007111:Immunity, Cellular; D007114:Immunization / Q000379:methods; D007071:Immunoglobulin A, Secretory / Q000097:blood; D007273:Injections, Intramuscular; D007378:Interleukins / Q000235:genetics; D016849:Keratitis, Herpetic / Q000276:immunology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal; D053758:Nanoparticles; D060888:Real-Time Polymerase Chain Reaction; D014611:Vaccination / Q000379:methods*; D019444:Vaccines, DNA / Q000008:administration & dosage*; D014759:Viral Envelope Proteins / Q000235:genetics; D000098546:Interleukin-21
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D016207:Cytokines; D004337:Drug Carriers; D007071:Immunoglobulin A, Secretory; D007378:Interleukins; D019444:Vaccines, DNA; D014759:Viral Envelope Proteins; C039447:glycoprotein D, Human herpesvirus 1; D000098546:Interleukin-21