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

• Published in: Journal of general virology 2007-01, Vol.88 (1), p.217-225
• Main Authors: Breton, Marie, Zhao, Chenqi, Ouellette, Marc, Tremblay, Michel J, Papadopoulou, Barbara
• Format: Article
• Language: English
• Subjects: AIDS Vaccines - administration & dosage; AIDS Vaccines - immunology; Animals; Antibody Specificity; Biological and medical sciences; Fundamental and applied biological sciences. Psychology; Gene Products, gag - administration & dosage; Gene Products, gag - biosynthesis; Gene Products, gag - genetics; Gene Products, gag - immunology; Genetic Vectors; HIV Infections - prevention & control; HIV-1 - genetics; HIV-1 - immunology; Humans; Immunity, Cellular; Leishmania - genetics; Mice; Mice, Inbred BALB C; Microbiology; Miscellaneous; Replicative cycle, interference, host-virus relations, pathogenicity, miscellaneous strains; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies; Vaccines, Synthetic; Virology; Virus Replication
• ISSN: 0022-1317; 1465-2099
• DOI: 10.1099/vir.0.81995-0

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 Correspondence Barbara Papadopoulou barbara.papadopoulou{at}crchul.ulaval.ca 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.