The specificity of targeted vaccines for APC surface molecules influences the immune response phenotype.
Different diseases require different immune responses for efficient protection. Thus, prophylactic vaccines should prime the immune system for the particular type of response needed for protection against a given infectious agent. We have here tested fusion DNA vaccines which encode proteins that bivalently target influenza hemagglutinins (HA) to different surface molecules on antigen presenting cells (APC). We demonstrate that targeting to MHC class II molecules predominantly induced an antibody/Th2 response, whereas targeting to CCR1/3/5 predominantly induced a CD8(+)/Th1 T cell response. With respect to antibodies, the polarizing effect was even more pronounced upon intramuscular (i.m) delivery as compared to intradermal (i.d.) vaccination. Despite these differences in induced immune responses, both vaccines protected against a viral challenge with influenza H1N1. Substitution of HA with ovalbumin (OVA) demonstrated that polarization of immune responses, as a consequence of APC targeting specificity, could be extended to other antigens. Taken together, the results demonstrate that vaccination can be tailor-made to induce a particular phenotype of adaptive immune responses by specifically targeting different surface molecules on APCs.
Institute of Immunology, University of Oslo and Oslo University Hospital, Oslo, Norway ; K.G. Jebsen Centre for Influenza Vaccine Research, University of Oslo, Oslo, Norway.
Gunnveig
G
Grødeland
Siri
S
Mjaaland
Gro
G
Tunheim
Agnete B
AB
Fredriksen
Bjarne
B
Bogen
D056704:Adaptive Immunity / Q000187:drug effects; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D017951:Antigen Presentation; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D005260:Female; D015870:Gene Expression; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D007271:Injections, Intradermal; D007273:Injections, Intramuscular; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control*; D010047:Ovalbumin / Q000235:genetics / Q000276:immunology; D054388:Receptors, CCR / Q000235:genetics / Q000276:immunology; D018417:Th1 Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D018418:Th2 Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D014611:Vaccination; D014614:Vaccines, Synthetic
D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D000949:Histocompatibility Antigens Class II; D007252:Influenza Vaccines; D054388:Receptors, CCR; D014614:Vaccines, Synthetic; D010047:Ovalbumin