Immunogenicity and efficacy of immunodeficiency virus-like particles pseudotyped with the G protein of vesicular stomatitis virus
- Department of Molecular and Medical Virology, Ruhr-University Bochum, D-44780 Bochum (Germany)
- German Primate Center, D-37077 Goettingen (Germany)
- Department of Hygiene and Social Medicine, Medical University Innsbruck, A-6020 Innsbruck (Austria)
- Institute of Medical Microbiology and Hygiene, University of Regensburg, D-93053 Regensburg (Germany)
- Department of Medical Microbiology and Infection Immunology, Charite - University Medicine of Berlin, D-12203 Berlin (Germany)
- Robert Koch-Institut, D-13353 Berlin (Germany)
- Department of Pathology, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg (Germany)
- Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, NY 10021-6399 (United States)
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.
- OSTI ID:
- 20850535
- Journal Information:
- Virology, Vol. 351, Issue 1; Other Information: DOI: 10.1016/j.virol.2006.03.009; PII: S0042-6822(06)00175-9; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0042-6822
- Country of Publication:
- United States
- Language:
- English
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