title: A single-cycle vaccine vector based on vesicular stomatitis virus can induce immune responses comparable to those generated by a replication-competent vector.
abstract: Live attenuated vaccine vectors based on recombinant vesicular stomatitis virus (VSV) are effective in several viral disease models. In this study, we asked if a VSV vector capable of only a single cycle of replication might be an effective alternative to replication-competent VSV vectors. We compared the cellular immune responses to human immunodeficiency virus (HIV) envelope protein (Env) expressed by replication-competent and single-cycle VSV vectors and also examined the antibody response to Env. The single-cycle vector was grown by complementation with VSV G protein and then tested initially for immunogenicity when given by four different routes. When given by the intramuscular route in mice, we found that the single-cycle vector was equivalent to the replication-competent VSV vector in generating high-level primary and memory CD8 T-cell responses as well as antibody responses to Env. Cellular responses were analyzed using major histocompatibility complex class I tetramers and direct measurement of cytotoxic T-lymphocyte activity in vivo. We also found that the recall responses after boosting were equivalent in animals vaccinated with replication-competent or single-cycle vectors. Additionally, we observed recall and heightened memory responses after boosting animals with a single-cycle vector complemented with G protein from a different vesiculovirus. Because expression of HIV Env by G-deleted VSV might allow replication in human cells expressing CD4, we generated a single-cycle VSV recombinant expressing a secreted form of the HIV Env protein. This virus was just as effective as the recombinant expressing the membrane-anchored Env protein at producing CD8 T cells and antibody responses.
authors.affiliation: Section of Microbial Pathogenesis, Yale University School of Medicine, 310 Cedar St. (LH 315), New Haven, CT 06510, USA.
authors.forename: Jean
authors.initials: J
authors.lastname: Publicover
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Ramsburg
authors.forename: John K
authors.initials: JK
authors.lastname: Rose
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D019040:E-Selectin / Q000032:analysis; D005260:Female; D005822:Genetic Vectors / Q000008:administration & dosage / Q000378:metabolism*; D006023:Glycoproteins / Q000276:immunology*; D015395:Histocompatibility Antigens Class I; D007117:Immunization, Secondary; D007156:Immunologic Memory; D007273:Injections, Intramuscular; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D008213:Lymphocyte Activation; D051379:Mice; D009500:Neutralization Tests; D013154:Spleen / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014611:Vaccination; D014721:Vesicular stomatitis Indiana virus / Q000378:metabolism*
chemical_list: D016915:AIDS Vaccines; D000914:Antibodies, Viral; D019040:E-Selectin; C033904:GP 140; D006023:Glycoproteins; D015395:Histocompatibility Antigens Class I