title: A vesicular stomatitis virus-based hepatitis B virus vaccine vector provides protection against challenge in a single dose.
abstract: As one of the world's most common infectious diseases, hepatitis B virus (HBV) is a serious worldwide public health problem, with HBV-associated liver disease accounting for more than half a million deaths each year. Although there is an effective prophylactic vaccine currently available to prevent infection, it has a number of characteristics that are suboptimal: multiple doses are needed to induce long-lasting immunity, immunity declines over time, it does not elicit protection in some individuals, and it is not effective therapeutically. We produced a recombinant vesicular stomatitis virus (VSV)-based vaccine vector expressing the HBV middle envelope surface protein (MS) and found that this vector was able to efficiently generate a strong HBs-specific antibody response following a single immunization in mice. A single immunization with the VSV-MS vector also induced robust CD8 T-cell activation. The CD8 T-cell response was greater in magnitude and broader in specificity than the response generated by a vaccinia virus-based vaccine vector or by recombinant protein immunization. Furthermore, a single VSV-MS immunization provided protection against virus challenge in mice. Given the similar antibody titers and superior T-cell responses elicited from a single immunization, a VSV-based HBV vaccine may have advantages over the current recombinant protein vaccine.
authors.affiliation: Department of Pathology, Yale University School of Medicine, New Haven, Conneticut 06520-8023, USA.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Cobleigh
authors.forename: Linda
authors.initials: L
authors.lastname: Buonocore
authors.forename: Susan L
authors.initials: SL
authors.lastname: Uprichard
authors.forename: John K
authors.initials: JK
authors.lastname: Rose
authors.forename: Michael D
authors.initials: MD
authors.lastname: Robek
mesh_terms: D000818:Animals; D001835:Body Weight; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005822:Genetic Vectors; D006509:Hepatitis B / Q000473:pathology / Q000517:prevention & control*; D006510:Hepatitis B Antibodies / Q000097:blood; D017325:Hepatitis B Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology*; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D014611:Vaccination / Q000379:methods*; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics; D018116:Vesiculovirus / Q000235:genetics*
chemical_list: D006510:Hepatitis B Antibodies; D017325:Hepatitis B Vaccines; D014614:Vaccines, Synthetic; D007371:Interferon-gamma