title: Single-dose, virus-vectored vaccine protection against Yersinia pestis challenge: CD4+ cells are required at the time of challenge for optimal protection.
abstract: We have developed an experimental recombinant vesicular stomatitis virus (VSV) vectored plague vaccine expressing a secreted form of Yersinia pestis low calcium response protein V (LcrV) from the first position of the VSV genome. This vector, given intramuscularly in a single dose, induced high-level antibody titers to LcrV and gave 90-100% protection against pneumonic plague challenge in mice. This single-dose protection was significantly better than that generated by VSV expressing the non-secreted LcrV protein. Increased protection correlated with increased anti-LcrV antibody and a bias toward IgG2a and away from IgG1 isotypes. We also found that the depletion of CD4+ cells, but not CD8+ cells, at the time of challenge resulted in reduced vaccine protection, indicating a role for cellular immunity in protection.
authors.affiliation: Department of Pathology, Yale University School of Medicine, 310 Cedar Street LH 315, New Haven, CT 06510, USA.
authors.forename: Anasuya
authors.initials: A
authors.lastname: Chattopadhyay
authors.forename: Steven
authors.initials: S
authors.lastname: Park
authors.forename: Guillaume
authors.initials: G
authors.lastname: Delmas
authors.forename: Rema
authors.initials: R
authors.lastname: Suresh
authors.forename: Svetlana
authors.initials: S
authors.lastname: Senina
authors.forename: David S
authors.initials: DS
authors.lastname: Perlin
authors.forename: John K
authors.initials: JK
authors.lastname: Rose
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D005260:Female; D005822:Genetic Vectors; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010930:Plague / Q000382:microbiology / Q000473:pathology / Q000517:prevention & control*; D010931:Plague Vaccine / Q000008:administration & dosage* / Q000235:genetics; D052899:Pore Forming Cytotoxic Proteins / Q000235:genetics / Q000276:immunology*; D014616:Vaccinia virus / Q000235:genetics*; D015010:Yersinia pestis / Q000276:immunology / Q000472:pathogenicity*
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; C043908:LcrV protein, Yersinia; D010931:Plague Vaccine; D052899:Pore Forming Cytotoxic Proteins