Co-immunization with M-CSFR and mM-CSF DNA vaccines is better than M-CSFR-mM-CSF fusion DNA vaccine.
OBJECTIVE
DNA vaccine against macrophage colony-stimulating factor receptor (M-CSFR) has shown both protective and therapeutic effects. In this study, we explore the possibility of using DNA vaccines against both M-CSFR and membrane-bound macrophage colony-stimulating factor (mM-CSF) to achieve better effects.


METHODS
Three plasmids were constructed by inserting either extracellular and transmembrane region of mM-CSF (pM), or extracellular region of M-CSFR (pR), or extracellular region of M-CSFR linked with extracellular and transmembrane regions of mM-CSF by a (Gly Gly Ser)2 flexible linker (pF), into pcDNA3.1. A SP2/0 cell line stably expressing pF (SP2/0-F) was established to evaluate humoral and cytotoxic immune responses as well as therapeutic and preventive effects induced by pM, pR, pF or pM+pR vaccination in BALB/c mice. The mechanisms of these vaccinations were also studied by monitoring the release of interleukin (IL)-4 and interferon (IFN)-g by splenocytes upon activation.


RESULTS
Vaccination against two epitopes had better effects than against a single epitope while vaccination by pM+pR had the greatest effects on inducing humoral and cytotoxic immune responses, prolonging survival of mice challenged with SP2/0-F, and inducing IL-4 and IFN-g release by splenocytes.


CONCLUSIONS
Our results suggest that co-immunization of M-CSFR and mM-CSF DNA vaccines is better than M-CSFR-mM-CSF fusion DNA vaccine.
D000818:Animals; D015153:Blotting, Western; D019556:COS Cells; D019496:Cancer Vaccines; D002462:Cell Membrane / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000188:drug therapy; D010957:Plasmids / Q000378:metabolism; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000166:cytology; D013997:Time Factors; D014162:Transfection; D014407:Tumor Cells, Cultured; D019444:Vaccines, DNA
D019496:Cancer Vaccines; D016207:Cytokines; D000939:Epitopes; D019444:Vaccines, DNA; D015847:Interleukin-4; D007371:Interferon-gamma; D016186:Receptor, Macrophage Colony-Stimulating Factor