A peptide-loaded dendritic cell based cytotoxic T-lymphocyte (CTL) vaccination strategy using peptides that span SIV Tat, Rev, and Env overlapping reading frames.
CTL based vaccine strategies in the macaque model of AIDS have shown promise in slowing the progression to disease. However, rapid CTL escape viruses can emerge rendering such vaccination useless. We hypothesized that such escape is made more difficult if the immunizing CTL epitope falls within a region of the virus that has a high density of overlapping reading frames which encode several viral proteins. To test this hypothesis, we immunized macaques using a peptide-loaded dendritic cell approach employing epitopes in the second coding exon of SIV Tat which spans reading frames for both Env and Rev. We report here that autologous dendritic cells, loaded with SIV peptides from Tat, Rev, and Env, induced a distinct cellular immune response measurable ex vivo. However, conclusive in vivo control of a challenge inoculation of SIVmac239 was not observed suggesting that CTL epitopes within densely overlapping reading frames are also subject to escape mutations.
Klase
Zachary
Z
Department of Infectious Diseases, Saint Michael's Medical Center, Newark, New Jersey, USA. zklase@gwu.edu
Donio
Michael J
MJ
Blauvelt
Andrew
A
Marx
Preston A
PA
Jeang
Kuan-Teh
KT
Smith
Stephen M
SM
D000818:Animals; D018791:CD4 Lymphocyte Count; D017931:DNA Primers; D003713:Dendritic Cells / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D015686:Gene Products, env / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D015694:Gene Products, rev / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D015696:Gene Products, tat / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D009154:Mutation; D010446:Peptide Fragments / Q000276:immunology; D016133:Polymerase Chain Reaction; D016364:Reading Frames / Q000235:genetics*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014611:Vaccination; D022223:Vaccines, Subunit; D019562:Viral Load
D017931:DNA Primers; D015686:Gene Products, env; D015694:Gene Products, rev; D015696:Gene Products, tat; D010446:Peptide Fragments; D022223:Vaccines, Subunit