Protective antiviral immunity conferred by a nonintegrative lentiviral vector-based vaccine.
Lentiviral vectors are under intense scrutiny as unique candidate viral vector vaccines against tumor and aggressive pathogens because of their ability to initiate potent and durable specific immune responses. Strategies that alleviate safety concerns will facilitate the clinical developments involving lentiviral vectors. In this respect, the development of integration deficient lentiviral vectors circumvents the safety concerns relative to insertional mutagenesis and might pave the way for clinical applications in which gene transfer is targeted to non-dividing cells. We thus evaluated the potential use of nonintegrative lentiviral vectors as vaccination tools since the main targeted cell in vaccination procedures is the non-dividing dendritic cell (DC). In this study, we demonstrated that a single administration of nonintegrative vectors encoding a secreted form of the envelope of a virulent strain of West Nile Virus (WNV) induces a robust B cell response. Remarkably, nonintegrative lentiviral vectors fully protected mice from a challenge with a lethal dose of WNV and a single immunization was sufficient to induce early and long-lasting protective immunity. Thus, nonintegrative lentiviral vectors might represent a safe and efficacious vaccination platform for the development of prophylactic vaccines against infectious agents.
Coutant
Frédéric
F
Laboratoire de Virologie Moléculaire et Vectorologie, Institut Pasteur, Paris, France.
Frenkiel
Marie-Pascale
MP
Despres
Philippe
P
Charneau
Pierre
P
D000818:Animals; D000917:Antibody Formation / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000821:virology; D005822:Genetic Vectors; D006367:HeLa Cells; D006801:Humans; D016233:Immunotherapy, Active / Q000379:methods*; D016086:Lentivirus / Q000235:genetics* / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D014161:Transduction, Genetic; D019076:Transgenes; D014709:Vero Cells; D014777:Virus Diseases / Q000276:immunology / Q000517:prevention & control*; D016662:Virus Integration / Q000235:genetics / Q000502:physiology; D014901:West Nile Fever / Q000401:mortality / Q000517:prevention & control / Q000662:veterinary / Q000821:virology; D053060:West Nile Virus Vaccines / Q000235:genetics; D014902:West Nile virus / Q000276:immunology
D053060:West Nile Virus Vaccines