title: Immunomodulator-based enhancement of anti smallpox immune responses.
abstract: BACKGROUND
  The current live vaccinia virus vaccine used in the prevention of smallpox is contraindicated for millions of immune-compromised individuals. Although vaccination with the current smallpox vaccine produces protective immunity, it might result in mild to serious health complications for some vaccinees. Thus, there is a critical need for the production of a safe virus-free vaccine against smallpox that is available to everyone. For that reason, we investigated the impact of imiquimod and resiquimod (Toll-like receptors agonists), and the codon-usage optimization of the vaccinia virus A27L gene in the enhancement of the immune response, with intent of producing a safe, virus-free DNA vaccine coding for the A27 vaccinia virus protein.
  
  
  METHODS
  We analyzed the cellular-immune response by measuring the IFN-γ production of splenocytes by ELISPOT, the humoral-immune responses measuring total IgG and IgG2a/IgG1 ratios by ELISA, and the TH1 and TH2 cytokine profiles by ELISA, in mice immunized with our vaccine formulation.
  
  
  RESULTS
  The proposed vaccine formulation enhanced the A27L vaccine-mediated production of IFN-γ on mouse spleens, and increased the humoral immunity with a TH1-biased response. Also, our vaccine induced a TH1 cytokine milieu, which is important against viral infections.
  
  
  CONCLUSIONS
  These results support the efforts to find a new mechanism to enhance an immune response against smallpox, through the implementation of a safe, virus-free DNA vaccination platform.
authors: Department of Microbiology, University of Puerto Rico, Medical Sciences Campus, San Juan, Puerto Rico.
authors: Osmarie
authors: O
authors: Martínez
authors: Department of Microbiology, University of Puerto Rico, Medical Sciences Campus, San Juan, Puerto Rico; Department of Microbiology Universidad Central del Caribe School of Medicine, Bayamón, Puerto Rico.
authors: Eric
authors: E
authors: Miranda
authors: Department of Microbiology, University of Puerto Rico, Medical Sciences Campus, San Juan, Puerto Rico.
authors: Maite
authors: M
authors: Ramírez
authors: Department of Microbiology, University of Puerto Rico, Medical Sciences Campus, San Juan, Puerto Rico.
authors: Saritza
authors: S
authors: Santos
authors: Department Biology, University of Puerto Rico, Rio Piedras Campus, San Juan, Puerto Rico.
authors: Carlos
authors: C
authors: Rivera
authors: Department Biology, University of Puerto Rico, Rio Piedras Campus, San Juan, Puerto Rico.
authors: Luis
authors: L
authors: Vázquez
authors: Department Biology, University of Puerto Rico, Rio Piedras Campus, San Juan, Puerto Rico.
authors: Tomás
authors: T
authors: Sánchez
authors: Department of Biology, University of Puerto Rico, Humacao, Puerto Rico; Department of Biology, University of Puerto Rico, Rio Piedras Campus, San Juan, Puerto Rico; Center for Applied Tropical Ecology and Conservation, University of Puerto Rico, Rio Piedras campus, San Juan, Puerto Rico.
authors: Raymond L
authors: RL
authors: Tremblay
authors: Department of Microbiology Universidad Central del Caribe School of Medicine, Bayamón, Puerto Rico.
authors: Eddy
authors: E
authors: Ríos-Olivares
authors: Department of Microbiology, University of Puerto Rico, Medical Sciences Campus, San Juan, Puerto Rico.
authors: Miguel
authors: M
authors: Otero
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D058501:Enzyme-Linked Immunospot Assay; D018604:Epitope Mapping; D005260:Female; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007132:Immunoglobulin Isotypes / Q000276:immunology; D007155:Immunologic Factors / Q000008:administration & dosage*; D051379:Mice; D012899:Smallpox / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control; D012900:Smallpox Vaccine / Q000235:genetics / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology; D012901:Variola virus / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D000956:Antigens, Viral; D016207:Cytokines; D007132:Immunoglobulin Isotypes; D007155:Immunologic Factors; D012900:Smallpox Vaccine; D014614:Vaccines, Synthetic