Induction of HIV-specific T and B cell responses with a replicating and conditionally infectious lentiviral vaccine.
The development of an HIV vaccine that induces broad and potent immunity is critically needed. Viruses, including lentiviruses, have been used as vectors for ex vivo transduction of antigens into dendritic cells (DC). We hypothesized that DC transduced with a vector that allows selective infection of DC could induce potent immunity by continually priming DC. A lentiviral vector encoding HIV gag-pol without env would form viral cores in transduced DC, but would release non-infectious particles by budding into endosomes and releasing apoptotic bodies or exosomes containing viral cores. DC function by endocytosing DC-derived apoptotic bodies, and they are specialized in their ability to move endocytic contents into the cytoplasm. We postulated that endocytosis of vector cores could lead to transduction of a second round of DC. In this report, we demonstrate accumulation of viral cores inside transduced DC and show second-round transduction of immature DC that endocytose transduced DC in vitro. The effectiveness of immunization of mice with transduced DC to induce specific lymphocyte activation was assessed. Mice developed antigen-specific T cell responses and specific antibodies after immunization. Transduction of DC with a replication-competent but conditionally infectious lentivirus could be a novel vaccine strategy for HIV.
Wingard
Jeremy B
JB
Duke University School of Medicine, Durham, NC, USA.
Anderson
Bart
B
Weissman
Drew
D
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000378:metabolism / Q000637:transplantation / Q000821:virology; D005260:Female; D015685:Fusion Proteins, gag-pol / Q000235:genetics / Q000276:immunology; D005822:Genetic Vectors / Q000235:genetics; D006678:HIV / Q000276:immunology; D016655:HIV Core Protein p24 / Q000276:immunology / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D016086:Lentivirus / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008854:Microscopy, Electron; D019251:Nucleocapsid / Q000096:biosynthesis / Q000648:ultrastructure; D011498:Protein Precursors / Q000032:analysis / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*; D014161:Transduction, Genetic; D014611:Vaccination / Q000379:methods*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000276:immunology
D016915:AIDS Vaccines; D015685:Fusion Proteins, gag-pol; D016655:HIV Core Protein p24; D011498:Protein Precursors; D019444:Vaccines, DNA; D054301:gag Gene Products, Human Immunodeficiency Virus; C059767:p55 gag precursor protein, Human immunodeficiency virus 1; D007371:Interferon-gamma