A recombinant non-pathogenic Leishmania vaccine expressing human immunodeficiency virus 1 (HIV-1) Gag elicits cell-mediated immunity in mice and decreases HIV-1 replication in human tonsillar tissue following exposure to HIV-1 infection.
Live-vector human immunodeficiency virus (HIV) vaccines are an integral part of a number of HIV vaccine regimens currently under evaluation that have yielded promising results in pre-clinical testing. In this report, a non-pathogenic protozoan parasitic vector, Leishmania tarentolae, which shares common target cells with HIV-1, was used to express full-length HIV-1 Gag protein. Immunization of BALB/c mice with recombinant L. tarentolae led to the expansion of HIV-1 Gag-specific T cells and stimulated CD8(+) T cells to produce gamma interferon in response to specific viral Gag epitopes. A booster immunization with recombinant L. tarentolae elicited effector memory HIV-1 Gag-specific CD4(+) T lymphocytes and increased antibody titres against HIV-1 Gag. Most importantly, immunization of human tonsillar tissue cultured ex vivo with Gag-expressing L. tarentolae vaccine vector elicited a 75% decrease in virus replication following exposure of the immunized tonsils to HIV-1 infection. These results demonstrated that recombinant L. tarentolae is capable of eliciting effective immune responses in mice and human systems, respectively, and suggest that this novel non-pathogenic recombinant vaccine vector shows excellent promise as a vaccination strategy against HIV-1.
Breton
Marie
M
Research Centre in Infectious Diseases, CHUL Research Centre of Laval University and Department of Medical Biology, Faculty of Medicine, Laval University, QC G1V 4G2, Canada.
Zhao
Chenqi
C
Research Centre in Infectious Diseases, CHUL Research Centre of Laval University and Department of Medical Biology, Faculty of Medicine, Laval University, QC G1V 4G2, Canada.
Ouellette
Marc
M
Research Centre in Infectious Diseases, CHUL Research Centre of Laval University and Department of Medical Biology, Faculty of Medicine, Laval University, QC G1V 4G2, Canada.
Tremblay
Michel J
MJ
Research Centre in Infectious Diseases, CHUL Research Centre of Laval University and Department of Medical Biology, Faculty of Medicine, Laval University, QC G1V 4G2, Canada.
Papadopoulou
Barbara
B
Research Centre in Infectious Diseases, CHUL Research Centre of Laval University and Department of Medical Biology, Faculty of Medicine, Laval University, QC G1V 4G2, Canada.
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D000818:Animals; D000918:Antibody Specificity; D015683:Gene Products, gag / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D005822:Genetic Vectors; D015658:HIV Infections / Q000517:prevention & control*; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D007891:Leishmania / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D014614:Vaccines, Synthetic; D014779:Virus Replication
D016915:AIDS Vaccines; D015683:Gene Products, gag; D014614:Vaccines, Synthetic