Document Detail


Immunogenicity and efficacy of immunodeficiency virus-like particles pseudotyped with the G protein of vesicular stomatitis virus.
MedLine Citation:
PMID:  16616946     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Seraphin Kuate; Christiane Stahl-Hennig; Heribert Stoiber; Godwin Nchinda; Anja Floto; Monika Franz; Ulrike Sauermann; Simon Bredl; Ludwig Deml; Ralf Ignatius; Steve Norley; Paul Racz; Klara Tenner-Racz; Ralph M Steinman; Ralf Wagner; Klaus Uberla
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2006-04-17
Journal Detail:
Title:  Virology     Volume:  351     ISSN:  0042-6822     ISO Abbreviation:  Virology     Publication Date:  2006 Jul 
Date Detail:
Created Date:  2006-07-17     Completed Date:  2006-09-06     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0110674     Medline TA:  Virology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  133-44     Citation Subset:  IM    
Affiliation:
Department of Molecular and Medical Virology, Ruhr-University Bochum, D-44780 Bochum, Germany.
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MeSH Terms
Descriptor/Qualifier:
AIDS Vaccines / administration & dosage,  immunology*
Animals
Cell Line
Drug Administration Schedule
HIV Antibodies / blood
Humans
Macaca mulatta / immunology
Membrane Glycoproteins / genetics,  immunology*
Mice
RNA, Viral / blood
Time Factors
Vesicular stomatitis Indiana virus*
Viral Envelope Proteins / genetics,  immunology*
Viral Load
Virion / genetics,  immunology
Grant Support
ID/Acronym/Agency:
AI40874/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/AIDS Vaccines; 0/G protein, vesicular stomatitis virus; 0/HIV Antibodies; 0/Membrane Glycoproteins; 0/RNA, Viral; 0/Viral Envelope Proteins

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