HOMEPRODUCTSSERVICESCOMPANYCONTACTFAQResearchDictionaryPharmaMobileSign Up FREE or Login

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.
AuthorsSeraphin 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
JournalVirology (Virology) Vol. 351 Issue 1 Pg. 133-44 (Jul 20 2006) ISSN: 0042-6822 [Print] United States
PMID16616946 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • AIDS Vaccines
  • G protein, vesicular stomatitis virus
  • HIV Antibodies
  • Membrane Glycoproteins
  • RNA, Viral
  • Viral Envelope Proteins
Topics
  • 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)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!


Choose Username:
Email:
Password:
Verify Password: