title: Immunogenicity of hybrid DNA vaccines expressing hepatitis B core particles carrying human and simian immunodeficiency virus epitopes in mice and rhesus macaques.
abstract: An effective HIV vaccine will likely need to induce broad and potent CTL responses. Epitope-based vaccines offer significant potential for inducing multi-specific CTL, but often require conjugation to T helper epitopes or carrier moieties to induce significant responses. We tested hybrid DNA vaccines encoding one or more HIV or SIV CTL epitopes fused to a hepatitis B core antigen (HBcAg) carrier gene as a means to improve the immunogenicity of epitope-based DNA vaccines. Immunization of mice with a HBcAg-HIV epitope DNA vaccine induced CD8(+) T cell responses that significantly exceeded levels induced with DNA encoding either the whole HIV antigen or the epitope alone. In rhesus macaques, a multi-epitope hybrid HBcAg-SIV DNA vaccine induced CTL responses to 13 different epitopes, including 3 epitopes that were previously not detected in SIV-infected macaques. These data demonstrate that immunization with hybrid HBcAg-epitope DNA vaccines is an effective strategy to increase the magnitude and breadth of HIV-specific CTL responses.
authors.affiliation: PowderJect Vaccines Inc, Madison, WI 53562, USA. dfuller@pitt.edu
authors.forename: Deborah Heydenburg
authors.initials: DH
authors.lastname: Fuller
authors.forename: Tim
authors.initials: T
authors.lastname: Shipley
authors.forename: Todd M
authors.initials: TM
authors.lastname: Allen
authors.forename: James T
authors.initials: JT
authors.lastname: Fuller
authors.forename: Mary S
authors.initials: MS
authors.lastname: Wu
authors.forename: Helen
authors.initials: H
authors.lastname: Horton
authors.forename: Nancy
authors.initials: N
authors.lastname: Wilson
authors.forename: Georg
authors.initials: G
authors.lastname: Widera
authors.forename: David I
authors.initials: DI
authors.lastname: Watkins
mesh_terms: D016915:AIDS Vaccines / Q000235:genetics / Q000276:immunology; D000595:Amino Acid Sequence; D000818:Animals; D002522:Chlorocebus aethiops; D000939:Epitopes / Q000235:genetics; D005822:Genetic Vectors; D015488:HIV Antigens / Q000235:genetics* / Q000276:immunology*; D006512:Hepatitis B Core Antigens / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D066298:In Vitro Techniques; D008253:Macaca mulatta; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids / Q000235:genetics; D018449:SAIDS Vaccines / Q000235:genetics / Q000276:immunology; D015302:Simian Immunodeficiency Virus / Q000235:genetics* / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019444:Vaccines, DNA / Q000235:genetics* / Q000276:immunology*; D014709:Vero Cells
chemical_list: D016915:AIDS Vaccines; D000939:Epitopes; D015488:HIV Antigens; D006512:Hepatitis B Core Antigens; D018449:SAIDS Vaccines; D019444:Vaccines, DNA