Evaluation of SIV library vaccines with genetic cytokines in a macaque challenge.
Gene and expression library immunization make it possible to functionally test all the gene-encoded antigens of a pathogen in a host challenge system. This comprehensive method could generate new and better vaccine candidates. We constructed expression libraries from simian immunodeficiency virus (SIV) cDNA and genetically immunize monkeys with the libraries alone or with a low dose of plasmids encoding human IL-12 and GMCSF. Eight of twelve animals in the three test groups showed some anti-SIV immune response, whereas the controls did not. Six months after priming, monkeys were intravenously challenged with virulent SIVmac251. All were infected but animals in two groups vaccinated with SIV libraries showed a trend toward lower viral-loads, mitigated clinical disease, and higher survival rates than controls. Significantly, co-administering the GMCSF and IL-12-encoding plasmids worsened these measures of protection. This preliminary study should encourage further development of library-vaccine strategies and caution the use of cytokines as adjuvants.
Sykes
Kathryn F
KF
Center for Biomedical Inventions, University of Texas Southwestern Medical Center, Dallas, TX 75390-8153, USA. kathryn.sykes@elibio.com
Lewis
Mark G
MG
Squires
Burke
B
Johnston
Stephen Albert
SA
D000818:Animals; D004279:DNA, Viral / Q000276:immunology*; D015723:Gene Library; D005818:Genetic Engineering; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000276:immunology*; D006801:Humans; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology*; D008253:Macaca mulatta; D008562:Membrane Glycoproteins / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D018449:SAIDS Vaccines / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000235:genetics*; D019444:Vaccines, DNA / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000235:genetics*; D014766:Viremia
D004279:DNA, Viral; D008562:Membrane Glycoproteins; D018449:SAIDS Vaccines; D019444:Vaccines, DNA; D014759:Viral Envelope Proteins; C069623:gp120 protein, Simian immunodeficiency virus; D018664:Interleukin-12; D016178:Granulocyte-Macrophage Colony-Stimulating Factor