title: Targeting DNA vaccines to myeloid cells using a small peptide.
abstract: Targeting DNA vaccines to dendritic cells (DCs) greatly enhances immunity. Although several approaches have been used to target protein Ags to DCs, currently there is no method that targets DNA vaccines directly to DCs. Here, we show that a small peptide derived from the rabies virus glycoprotein fused to protamine residues (RVG-P) can target DNA to myeloid cells, including DCs, which results in enhanced humoral and T-cell responses. DCs targeted with a DNA vaccine encoding the immunodominant vaccinia B8R gene via RVG-P were able to restimulate vaccinia-specific memory T cells in vitro. Importantly, a single i.v. injection of B8R gene bound to RVG-P was able to prime a vaccinia-specific T-cell response that was able to rapidly clear a subsequent vaccinia challenge in mice. Moreover, delivery of DNA in DCs was enough to induce DC maturation and efficient Ag presentation without the need for adjuvants. Finally, immunization of mice with a DNA-vaccine encoding West Nile virus (WNV) prM and E proteins via RVG-P elicited high titers of WNV-neutralizing Abs that protected mice from lethal WNV challenge. Thus, RVG-P provides a reagent to target DNA vaccines to myeloid cells and elicit robust T-cell and humoral immune responses.
authors.affiliation: Center of Excellence in Infectious Disease Research, Department of Biomedical Sciences, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA.
authors.forename: Chunting
authors.initials: C
authors.lastname: Ye
authors.forename: Jang Gi
authors.initials: JG
authors.lastname: Choi
authors.forename: Sojan
authors.initials: S
authors.lastname: Abraham
authors.forename: Premlata
authors.initials: P
authors.lastname: Shankar
authors.forename: N
authors.initials: N
authors.lastname: Manjunath
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000821:virology; D005818:Genetic Engineering; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology; D007114:Immunization; D007156:Immunologic Memory; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010455:Peptides / Q000008:administration & dosage / Q000138:chemical synthesis / Q000276:immunology*; D011820:Rabies virus / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology* / Q000821:virology; D019444:Vaccines, DNA / Q000008:administration & dosage*; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage; D014901:West Nile Fever / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D014902:West Nile virus / Q000276:immunology*
chemical_list: D000956:Antigens, Viral; D006023:Glycoproteins; D010455:Peptides; D019444:Vaccines, DNA; D014764:Viral Proteins; D014765:Viral Vaccines
keywords: Antigen targeting; DNA vaccine; Dendritic cells; Immune response; Rabies virus glycoprotein peptide