Immunogenicity of hybrid DNA vaccines expressing hepatitis B core particles carrying human and simian immunodeficiency virus epitopes in mice and rhesus macaques.
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.
Fuller
Deborah Heydenburg
DH
PowderJect Vaccines Inc, Madison, WI 53562, USA. dfuller@pitt.edu
Shipley
Tim
T
Allen
Todd M
TM
Fuller
James T
JT
Wu
Mary S
MS
Horton
Helen
H
Wilson
Nancy
N
Widera
Georg
G
Watkins
David I
DI
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
D016915:AIDS Vaccines; D000939:Epitopes; D015488:HIV Antigens; D006512:Hepatitis B Core Antigens; D018449:SAIDS Vaccines; D019444:Vaccines, DNA