GP96 C-terminal improves Her2/neu DNA vaccine.
BACKGROUND
DNA vaccines ensure protective immunity against tumors in a variety of experimental models. The favorite target tumor-associated antigens have been those that are frequently expressed by human tumors, such as Her2. However, the efficacy of active vaccination is limited because Her2 is a self-tolerated antigen. Many strategies have been applied to increase the efficacy of DNA vaccination, such as fusion or co-administration of Her2 with cytokine and co-stimulatory molecules. GP96 is involved in innate and adaptive immune responses and evokes potent activation and maturation of dendritic cells along with increased secretion of pro-inflammatory cytokines. On the basis of previous studies, we expected the C-terminal of GP96 to act as a package and as a suitable substitute for both cytokine and co-stimulatory genes.


METHODS
In the present study, the C-terminal of GP96 fused or co-administered with Her2/neu-containing constructs was used and the resultant immune response was evaluated and compared.


RESULTS
The data obtained showed that the construct containing the C-terminal of GP96 fused with Her2/neu, but not the co-administration of the two separated constructs, decreased CD4(+)CD25(+)foxp3(+) regulatory T cells at the tumor site, enhanced cytotoxic T lymphocyte activity and increased interferon-gamma secretion.


CONCLUSIONS
The C-terminal of GP96 has potent adjuvant activity in eliciting a significant immune response when fused with Her2/neu. It may be used as molecular adjuvant along with other tumor or bacterial/viral antigens.
Pakravan
Nafiseh
N
Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Soleimanjahi
Hoorieh
H
Hassan
Zuhair Mohammad
ZM
D000276:Adjuvants, Immunologic / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D008562:Membrane Glycoproteins / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D051381:Rats; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology* / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D014611:Vaccination / Q000379:methods*; D019444:Vaccines, DNA / Q000276:immunology*
D000276:Adjuvants, Immunologic; D007371:Interferon-gamma; D008562:Membrane Glycoproteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D019444:Vaccines, DNA; C053387:endoplasmin