Abstract:
: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 beta-galactosidase (beta-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 beta-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 beta-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.
journal_name
Vaccinejournal_title
Vaccineauthors
Reali E,Canter D,Zeytin H,Schlom J,Greiner JWdoi
10.1016/j.vaccine.2004.11.060subject
Has Abstractpub_date
2005-04-22 00:00:00pages
2909-21issue
22eissn
0264-410Xissn
1873-2518pii
S0264-410X(04)00918-1journal_volume
23pub_type
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