Use of the mannan receptor to selectively target vaccine antigens for processing and antigen presentation through the MHC class I and class II pathways.
Extensive studies have shown that synthetic and recombinant vaccines developed against hemoparasites have not been as effective as whole parasites or crude membrane fractions in eliciting protective immunity. A possible reason is that synthetic vaccines are not being presented in a form that induces the appropriate immune response. We have developed a bovine model system to evaluate the ability of adjuvant compounds to induce an immune response to peptide antigens dominated by a cytokine profile with a Type 1 (cell-mediated) or Type 2 (humoral) bias. In the initial testing of this system, we found that mRNA expression of certain cytokines (interleukin [IL]-1beta, IL-6, IL-12, IL-15, GM-CSF, iNOS, and tumor necrosis factor [TNF]-alpha) is enhanced when monocyte-derived macrophages are stimulated with peptide antigen conjugated with mannan under oxidizing conditions compared to peptide conjugated with reduced mannan. The data suggest this model will be useful in identifying adjuvant systems that selectively modulate the cytokine profile of antigen presenting cells at the time of antigen presentation and the consequent downstream maturation of naive T cells to effector cells with Type 1 or Type 2 cytokine bias.
Davis
W C
WC
Department of Veterinary Microbiology and Pathology, CVM, Washington State University, Pullman, Washington 99164-7040, USA. davisw@mail.vetmed.wsu.edu
Konzek
R L
RL
Haas
K
K
Estes
D M
DM
Hamilton
M J
MJ
Call
D R
DR
Apostolopoulos
V
V
McKenzie
I F C
IF
D000276:Adjuvants, Immunologic; D000818:Animals; D000917:Antibody Formation; D017951:Antigen Presentation; D002417:Cattle / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D008264:Macrophages / Q000276:immunology; D008285:Major Histocompatibility Complex; D008954:Models, Biological; D010272:Parasitic Diseases / Q000517:prevention & control*; D012333:RNA, Messenger / Q000378:metabolism; D011975:Receptors, Mitogen / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014614:Vaccines, Synthetic
D000276:Adjuvants, Immunologic; D016207:Cytokines; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D012333:RNA, Messenger; D011975:Receptors, Mitogen; D014614:Vaccines, Synthetic; C037935:mannan receptor