Immunization with Th-CTL fusion peptide and cytosine-phosphate-guanine DNA in transgenic HLA-A2 mice induces recognition of HIV-infected T cells and clears vaccinia virus challenge.
We evaluated immunogenicity of a novel Th-CTL fusion peptide composed of the pan DR Th epitope and a CTL epitope derived from HIV-pol in two transgenic HLA-A*0201/K(b) mouse models. The immunogenicity of peptides of this structure is highly dependent on coadministered cytosine-phosphate-guanine DNA. Initial evaluations of peptide-specific immunity are based on results of chromium release assay, intracellular cytokine, and tetramer staining. Significant cytotoxic T cell responses are found upon a single immunization with as low as 0.1 nmol both peptide and cytosine-phosphate-guanine DNA. Splenocytes from immunized mice recognize naturally processed HIV-pol expressed from vaccinia virus (pol-VV). Translation of immunologic criteria into more relevant assays was pursued using systemic challenge of immunized mice with pol-VV. Only mice receiving both peptide and DNA together successfully cleared upward of 6 logs of virus from ovaries, compared with controls. Challenge with pol-VV by intranasal route of intranasal immunized mice showed a significant reduction in the levels of VV in lung compared with naive mice. A convincing demonstration of the relevance of these vaccines is the robust lysis of HIV-infected Jurkat T cells (JA2/R7/Hyg) by immune splenocytes from peptide- and DNA-immunized mice. This surprisingly effective immunization merits consideration for clinical evaluation, because it succeeded in causing immune recognition and lysis of cells infected with its target virus and reduction in titer of highly pathogenic VV.
Daftarian
Pirouz
P
Laboratory of Vaccine Research, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA.
Ali
Saima
S
Sharan
Rahul
R
Lacey
Simon F
SF
La Rosa
Corinna
C
Longmate
Jeff
J
Buck
Christopher
C
Siliciano
Robert F
RF
Diamond
Don J
DJ
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000235:genetics; D002478:Cells, Cultured; D018920:Coculture Techniques; D018899:CpG Islands / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage / Q000276:immunology*; D016655:HIV Core Protein p24 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D015789:HLA-A2 Antigen / Q000235:genetics* / Q000276:immunology; D006801:Humans; D018928:Immunity, Mucosal / Q000235:genetics; D007274:Injections, Intraperitoneal; D007371:Interferon-gamma / Q000096:biosynthesis; D007424:Intracellular Fluid / Q000276:immunology / Q000378:metabolism; D019169:Jurkat Cells; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009297:Nasal Mucosa / Q000276:immunology / Q000821:virology; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage / Q000276:immunology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism / Q000821:virology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism / Q000821:virology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*; D014615:Vaccinia / Q000276:immunology / Q000517:prevention & control*
D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D018984:Epitopes, T-Lymphocyte; D016655:HIV Core Protein p24; D015789:HLA-A2 Antigen; D017780:Malaria Vaccines; D009838:Oligodeoxyribonucleotides; C401223:PADRE 45; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D019444:Vaccines, DNA; D007371:Interferon-gamma