Enhancing efficacy of HIV Gag DNA vaccine by local delivery of GM-CSF in murine and macaque models

Ruijiang Song, Shuqin Liu, Robert J. Adams, Kam W. Leong

Research output: Contribution to journalArticle

Abstract

Controlled release of granulocyte-macrophage colony-stimulating factor (GM-CSF) protein by albumin-heparin microparticles administered via intramuscular vaccination in conjunction with HIV DNA vaccines stimulated HIV Gag-specific immune responses. In the murine model, Gag-specific cytotoxic T lymphocyte (CTL) and T helper (Th) responses were significantly enhanced by administration of murine GM-CSF microparticles. This effect was comparable to a GM-CSF encoded plasmid. In three of four rhesus monkeys, enhancement of Gag-specific antibody (Ab), Th, and CTL responses was observed 1 month after the first immunization with coadministration of human GM-CSF microparticles and HIV Gag plasmid. The second, third, and fourth booster immunizations, however, did not increase the Gag-specific immune responses. Subsequent application of Gag protein in complete Freund's adjuvant (CFA) significantly enhanced Ab and Th, but not CTL. However, Gag-specific CTL response was triggered by cytokine and Gag p55-encapsulated microparticles in all animals. The strategy of priming immune responses by coadministration of cytokine microparticles and DNA vaccines, followed by boosting with cytokine and antigen protein-encapsulated microparticles, may prove effective in improving an HIV DNA vaccine design.

Original languageEnglish (US)
Pages (from-to)380-389
Number of pages10
JournalJournal of Interferon and Cytokine Research
Volume26
Issue number6
DOIs
StatePublished - Jun 1 2006

ASJC Scopus subject areas

  • Immunology
  • Cell Biology
  • Virology

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