Genetically modified anthrax lethal toxin safely delivers whole HIV protein antigens into the cytosol to induce T cell immunity.
Bacillus anthrax lethal toxin can be engineered to deliver foreign proteins to the cytosol for antigen presentation to CD8 T cells. Vaccination with modified toxins carrying 8-9 amino acid peptide epitopes induces protective immunity in mice. To evaluate whether large protein antigens can be used with this system, recombinant constructs encoding several HIV antigens up to 500 amino acids were produced. These candidate HIV vaccines are safe in animals and induce CD8 T cells in mice. Constructs encoding gag p24 and nef stimulate gag-specific CD4 proliferation and a secondary cytotoxic T lymphocyte response in HIV-infected donor peripheral blood mononuclear cells in vitro. These results lay the foundation for future clinical vaccine studies.
Lu
Y
Y
Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA. yichenlu@hsph.harvard.edu
Friedman
R
R
Kushner
N
N
Doling
A
A
Thomas
L
L
Touzjian
N
N
Starnbach
M
M
Lieberman
J
J
D016915:AIDS Vaccines / Q000235:genetics / Q000276:immunology*; D000818:Animals; D017951:Antigen Presentation; D000942:Antigens, Bacterial; D001427:Bacterial Toxins / Q000235:genetics*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003600:Cytosol / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic; D004337:Drug Carriers; D015488:HIV Antigens / Q000235:genetics / Q000276:immunology*; D008264:Macrophages; D051379:Mice; D008807:Mice, Inbred BALB C; D015202:Protein Engineering; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000276:immunology; D014611:Vaccination
D016915:AIDS Vaccines; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D004337:Drug Carriers; D015488:HIV Antigens; D011993:Recombinant Fusion Proteins; C030325:anthrax toxin