Immunogenicity and efficacy of immunodeficiency virus-like particles pseudotyped with the G protein of vesicular stomatitis virus

• Published in: Virology (New York, N.Y.) N.Y.), 2006-07, Vol.351 (1), p.133-144
• Main Authors: Kuate, Seraphin, Stahl-Hennig, Christiane, Stoiber, Heribert, Nchinda, Godwin, Floto, Anja, Franz, Monika, Sauermann, Ulrike, Bredl, Simon, Deml, Ludwig, Ignatius, Ralf, Norley, Steve, Racz, Paul, Tenner-Racz, Klara, Steinman, Ralph M., Wagner, Ralf, Überla, Klaus
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; AIDS; AIDS Vaccines - administration & dosage; AIDS Vaccines - immunology; AIDS VIRUS; Animals; ANTIBODIES; ANTIGENS; Cell Line; Drug Administration Schedule; GTP-ASES; HIV; HIV Antibodies - blood; Human immunodeficiency virus 1; Humans; Immunization; INHIBITION; Macaca mulatta; Macaca mulatta - immunology; MACACUS; Membrane Glycoproteins - genetics; Membrane Glycoproteins - immunology; MICE; RNA, Viral - blood; Simian immunodeficiency virus; SIV; STIMULATION; Time Factors; Vaccine; VACCINES; Vesicular stomatitis Indiana virus; Vesicular stomatitis virus; Viral Envelope Proteins - genetics; Viral Envelope Proteins - immunology; Viral Load; Virion - genetics; Virion - immunology; VLP
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1016/j.virol.2006.03.009

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.