title: Pseudotyping lentiviral vectors with lymphocytic choriomeningitis virus glycoproteins for transduction of dendritic cells and in vivo immunization.
abstract: Lentiviral vectors (LVs) are promising delivery systems for gene therapy, and they can be further engineered to increase their potential for effectively delivering transgenes to desired cell populations. Here, we have engineered LVs pseudotyped with envelope glycoproteins derived from lymphocytic choriomeningitis virus (LCMV) for antigen delivery to elicit vaccine-directed immune responses. Two variants, LCMV-WE and LCMV-Arm53b, were evaluated for their ability to mediate LV-based cellular transduction in vitro. LCMV-WE with a leucine residue at position 260 (260L) is known for its high-affinity binding with a cellular receptor, α-dystroglycan (α-DG), whereas LCMV-Arm53b has low-affinity binding resulting from a phenylalanine residue at the same position. In contrast to LCMV-Arm53b, we found that LVs pseudotyped with LCMV-WE could transduce 293T cells and murine dendritic cells much more efficiently based, at least in part, on their favorable interaction with α-DG. In mice, LCMV-WE-bearing LVs encoding a model antigen, invariant chain ovalbumin, could elicit substantial antigen-specific CD8(+) T cell immune response. The response could be further enhanced by a homologous boosting immunization with the same vector. These findings offer evidence to support the potential utilization of LCMV-WE-bearing LVs for vectored vaccines against cancer and infectious diseases.
authors.affiliation: 1 Mork Family Department of Chemical Engineering and Materials Science, University of Southern California , Los Angeles, CA 90089.
authors.forename: Chupei
authors.initials: C
authors.lastname: Zhang
authors.forename: Biliang
authors.initials: B
authors.lastname: Hu
authors.forename: Liang
authors.initials: L
authors.lastname: Xiao
authors.forename: Yarong
authors.initials: Y
authors.lastname: Liu
authors.forename: Pin
authors.initials: P
authors.lastname: Wang
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D000941:Antigens / Q000008:administration & dosage; D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D049030:Dystroglycans / Q000378:metabolism; D005822:Genetic Vectors / Q000737:chemistry / Q000235:genetics*; D015497:HIV-1 / Q000737:chemistry / Q000235:genetics*; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D008217:Lymphocytic choriomeningitis virus / Q000737:chemistry*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010047:Ovalbumin / Q000235:genetics / Q000276:immunology*; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology*; D011485:Protein Binding; D011991:Receptors, Virus / Q000378:metabolism; D037182:T-Cell Antigen Receptor Specificity; D014161:Transduction, Genetic; D019076:Transgenes; D014614:Vaccines, Synthetic; D014763:Viral Matrix Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D000941:Antigens; D000944:Antigens, Differentiation, B-Lymphocyte; D000949:Histocompatibility Antigens Class II; D010446:Peptide Fragments; D011991:Receptors, Virus; D014614:Vaccines, Synthetic; D014763:Viral Matrix Proteins; C045084:invariant chain; D049030:Dystroglycans; D010047:Ovalbumin