Comparative studies of Avipox-GM-CSF versus recombinant GM-CSF protein as immune adjuvants with different vaccine platforms

• Published in: Vaccine Vol. 23; no. 22; pp. 2909 - 2921
• Main Authors: Reali, E., Canter, D., Zeytin, H., Schlom, J., Greiner, J.W.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 22.04.2005; Elsevier; Elsevier Limited
• Subjects: Animals; Applied microbiology; Avipox-GM-CSF; Avipoxvirus - genetics; Biological and medical sciences; Comparative studies; Cytokines; E coli; Female; Fundamental and applied biological sciences. Psychology; Granulocyte-Macrophage Colony-Stimulating Factor - administration & dosage; Granulocyte-Macrophage Colony-Stimulating Factor - blood; Granulocyte-Macrophage Colony-Stimulating Factor - immunology; Immune adjuvant; Immune system; Immunization; Injection; Injections; Lymph nodes; Medical research; Mice; Microbiology; Peptides; Poxvirus; Proteins; Recombinant Proteins - administration & dosage; Recombinant Proteins - immunology; Smallpox; Studies; T-Lymphocytes, Cytotoxic - immunology; Tumors; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Viruses; Immune adjuvant; Avipox-GM-CSF; Immunological adjuvant; Cytokine; Vaccine; Recombinant protein; Comparative study; Granulocyte macrophage colony stimulating factor
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2004.11.060

Granulocyte–macrophage colony-stimulating factor (GM-CSF) is a potent immune stimulant when administered with different vaccines. Optimal use of GM-CSF resides in its ability to act locally to stimulate the proliferation and maturation of professional antigen-presenting cells (APCs) (i.e., Langerhans’ cells) at the injection site. GM-CSF was engineered into a replication-incompetent recombinant avian (fowlpox) virus (rF-GM-CSF) and a single subcutaneous injection resulted in a sustained enrichment of activated dendritic cells within the regional draining lymph nodes. Those changes were attributed to local GM-CSF production at the injection site by rF-GM-CSF-infected cells. Studies were carried out in which mice were administered different types of β-galactosidase (β-gal)-based vaccines – whole protein, peptide, recombinant poxviruses – and GM-CSF was administered either as a single injection of rF-GM-CSF or four daily bolus injections of the recombinant protein. The use of rF-GM-CSF either improved the immune adjuvant effect, as observed for poxvirus-based vaccines, or was equivalent to rGM-CSF, as observed with the β-gal protein vaccine. It is important to note that with either the replication-competent (vaccinia) or replication-incompetent (fowlpox) vaccines expressing LacZ, strong CTL responses directed against β-gal were induced only when rF-GM-CSF was used as the immune adjuvant. Engineering GM-CSF into a recombinant fowlpox virus offers an excellent vehicle for the delivery of this cytokine as an immune adjuvant with specific vaccine platforms. In particular, delivery of GM-CSF via the rF-GM-CSF construct would be preferred over bolus injections of rGM-CSF when used as an immune adjuvant with whole protein or recombinant poxvirus-based vaccines. The study underscores the importance of defining the appropriate delivery form of an immune adjuvant, such as GM-CSF, relative to the immunization strategy to maximize the host immune responses against a specific antigen.