The specificity of targeted vaccines for APC surface molecules influences the immune response phenotype

• Published in: PloS one 2013-11, Vol.8 (11), p.e80008-e80008
• Main Authors: Grødeland, Gunnveig, Mjaaland, Siri, Tunheim, Gro, Fredriksen, Agnete B, Bogen, Bjarne
• Format: Article
• Language: English
• Subjects: Adaptive immunity; Adaptive Immunity - drug effects; Animals; Antibodies; Antibodies, Viral - biosynthesis; Antigen Presentation; Antigen-presenting cells; Antigens; B cells; Biosafety; CC chemokine receptors; CCR1 protein; CD8 antigen; Chemokines; Cloning; Comparative analysis; Cytokines; Cytotoxicity; Dendritic cells; Dendritic Cells - cytology; Dendritic Cells - drug effects; Dendritic Cells - immunology; Deoxyribonucleic acid; DNA; DNA vaccines; Female; Gene Expression; Genotype & phenotype; Hemagglutinin Glycoproteins, Influenza Virus - genetics; Hemagglutinin Glycoproteins, Influenza Virus - immunology; Hemagglutinins; Histocompatibility Antigens Class II - genetics; Histocompatibility Antigens Class II - immunology; Immune response; Immune system; Immunology; Influenza; Influenza A Virus, H1N1 Subtype - immunology; Influenza vaccines; Influenza Vaccines - administration & dosage; Influenza Vaccines - genetics; Influenza Vaccines - immunology; Injections, Intradermal; Injections, Intramuscular; Ligands; Lymphocytes; Lymphocytes T; Major histocompatibility complex; Mice; Mice, Inbred BALB C; Orthomyxoviridae Infections - immunology; Orthomyxoviridae Infections - prevention & control; Ovalbumin; Ovalbumin - genetics; Ovalbumin - immunology; Phenotypes; Polarization; Proteins; Receptors, CCR - genetics; Receptors, CCR - immunology; T cell receptors; T cells; Th1 Cells - cytology; Th1 Cells - drug effects; Th1 Cells - immunology; Th2 Cells - cytology; Th2 Cells - drug effects; Th2 Cells - immunology; Transcription factors; Vaccination; Vaccines; Vaccines, Synthetic
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0080008

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.