Immunogenicity and efficacy of immunodeficiency virus-like particles pseudotyped with the G protein of vesicular stomatitis virus.
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.
Kuate
Seraphin
S
Department of Molecular and Medical Virology, Ruhr-University Bochum, D-44780 Bochum, Germany.
Stahl-Hennig
Christiane
C
Stoiber
Heribert
H
Nchinda
Godwin
G
Floto
Anja
A
Franz
Monika
M
Sauermann
Ulrike
U
Bredl
Simon
S
Deml
Ludwig
L
Ignatius
Ralf
R
Norley
Steve
S
Racz
Paul
P
Tenner-Racz
Klara
K
Steinman
Ralph M
RM
Wagner
Ralf
R
Uberla
Klaus
K
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
D016915:AIDS Vaccines; C028391:G protein, vesicular stomatitis virus; D015483:HIV Antibodies; D008562:Membrane Glycoproteins; D012367:RNA, Viral; D014759:Viral Envelope Proteins