Evaluation of SIV library vaccines with genetic cytokines in a macaque challenge

Kathryn F. Sykes, Mark G. Lewis, Burke Squires, Stephen Albert Johnston

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2382-2395
Number of pages14
JournalVaccine
Volume20
Issue number17-18
DOIs
StatePublished - May 22 2002
Externally publishedYes

Keywords

  • ELI
  • Genetic adjuvants
  • SIV trial

ASJC Scopus subject areas

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

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