Vaccines delivered by integration-deficient lentiviral vectors targeting dendritic cells induces strong antigen-specific immunity.
We report a study of an integration-deficient lentiviral vector (IDLV) enveloped with a Sindbis virus glycoprotein mutant (SVGmu) capable of selectively binding to dendritic cells (DCs) for its potential as a vaccine carrier. The in vitro assays showed that the D64V point mutation in the catalytic domain of HIV-1 integrase efficiently inhibited the integration of the transgene upon vector transduction, while the targeting specificity of the vector to preferentially transduce and mediate durable expression in DCs was maintained. Substantial immune responses in C57BL/6 mice and complete protection against a challenge with the C57BL/6 thymoma EG.7 tumor expressing a delivered ovalbumin (OVA) antigen in mice have been achieved through the direct injection of the DC-directed IDLV encoding OVA. Thus, this DC-directed IDLV system represents a promising and efficient vector platform with remarkably improved safety for the future development of DC-based immunotherapy.
Hu
Biliang
B
Mork Family Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, CA 90089, USA.
Dai
Bingbing
B
Wang
Pin
P
D000818:Animals; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D005822:Genetic Vectors; D019427:HIV Integrase / Q000235:genetics / Q000276:immunology; D016086:Lentivirus / Q000276:immunology / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D017354:Point Mutation; D013945:Thymoma / Q000276:immunology / Q000517:prevention & control*; D014161:Transduction, Genetic; D019076:Transgenes; D016662:Virus Integration; D058951:gp100 Melanoma Antigen / Q000276:immunology
D019496:Cancer Vaccines; D058951:gp100 Melanoma Antigen; D019427:HIV Integrase; C514801:p31 integrase protein, Human immunodeficiency virus 1