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: 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
• Journal: Virology (Virology) Vol. 351 Issue 1 Pg. 133-44 (Jul 20 2006) ISSN: 0042-6822 [Print] United States
• PMID: 16616946 (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)