title: Immunogenicity and efficacy of immunodeficiency virus-like particles pseudotyped with the G protein of vesicular stomatitis virus.
abstract: Vaccination with exogenous antigens such as recombinant viral proteins, immunodeficiency virus-derived whole inactivated virus particles, or virus-like particles (VLP) has generally failed to provide sufficient protection in animal models for AIDS. Pseudotyping VLPs with the vesicular stomatitis virus G protein (VSV-G), which is known to mediate entry into dendritic cells, might allow more efficient stimulation of immune responses. Therefore, we pseudotyped noninfectious immunodeficiency virus-like particles with VSV-G and carried out a preliminary screen of their immunogenicity and vaccination efficacy. Incorporation of VSV-G into HIV-1 VLPs led to hundred-fold higher antibody titers to HIV-1 Gag and enhancement of T cell responses in mice. Repeated vaccination of rhesus monkeys for 65 weeks with VSV-G pseudotyped simian immunodeficiency virus (SIV)-like particles (VLP[G]) provided initial evidence for efficient suppression of viral load after mucosal challenge with the SIVmac239 virus. Challenge of monkeys after a 28 week vaccination regimen with VLP[G] led to a reduction in peak viremia, but persistent suppression of viral load was not achieved. Due to limitations in the number of animals available for this study, improved efficacy of VSV-G pseudotyped VLPs in nonhuman primates could not be demonstrated. However, mouse experiments revealed that pseudotyping of VLPs with fusion-competent VSV-G clearly improves their immunogenicity. Additional strategies, particularly adjuvants, should be considered to provide greater protection against a challenge with pathogenic immunodeficiency virus.
authors.affiliation: Department of Molecular and Medical Virology, Ruhr-University Bochum, D-44780 Bochum, Germany.
authors.forename: Seraphin
authors.initials: S
authors.lastname: Kuate
authors.forename: Christiane
authors.initials: C
authors.lastname: Stahl-Hennig
authors.forename: Heribert
authors.initials: H
authors.lastname: Stoiber
authors.forename: Godwin
authors.initials: G
authors.lastname: Nchinda
authors.forename: Anja
authors.initials: A
authors.lastname: Floto
authors.forename: Monika
authors.initials: M
authors.lastname: Franz
authors.forename: Ulrike
authors.initials: U
authors.lastname: Sauermann
authors.forename: Simon
authors.initials: S
authors.lastname: Bredl
authors.forename: Ludwig
authors.initials: L
authors.lastname: Deml
authors.forename: Ralf
authors.initials: R
authors.lastname: Ignatius
authors.forename: Steve
authors.initials: S
authors.lastname: Norley
authors.forename: Paul
authors.initials: P
authors.lastname: Racz
authors.forename: Klara
authors.initials: K
authors.lastname: Tenner-Racz
authors.forename: Ralph M
authors.initials: RM
authors.lastname: Steinman
authors.forename: Ralf
authors.initials: R
authors.lastname: Wagner
authors.forename: Klaus
authors.initials: K
authors.lastname: Uberla
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D000818:Animals; D002460:Cell Line; D004334:Drug Administration Schedule; D015483:HIV Antibodies / Q000097:blood; D006801:Humans; D008253:Macaca mulatta / Q000276:immunology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D012367:RNA, Viral / Q000097:blood; D013997:Time Factors; D014721:Vesicular stomatitis Indiana virus; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology*; D019562:Viral Load; D014771:Virion / Q000235:genetics / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; C028391:G protein, vesicular stomatitis virus; D015483:HIV Antibodies; D008562:Membrane Glycoproteins; D012367:RNA, Viral; D014759:Viral Envelope Proteins