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


Journal Article

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.

Full Text

Cited Authors

  • Song, R; Liu, S; Adams, RJ; Leong, KW

Published Date

  • June 2006

Published In

Volume / Issue

  • 26 / 6

Start / End Page

  • 380 - 389

PubMed ID

  • 16734558

Pubmed Central ID

  • 16734558

Electronic International Standard Serial Number (EISSN)

  • 1557-7465

International Standard Serial Number (ISSN)

  • 1079-9907

Digital Object Identifier (DOI)

  • 10.1089/jir.2006.26.380


  • eng