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PLOS ONE 2013

The Specificity of Targeted Vaccines for APC Surface Molecules Influences the Immune Response Phenotype

DOI: 10.1371/journal.pone.0080008

Gunnveig Gr？deland, Siri Mjaaland, Gro Tunheim, Agnete B. Fredriksen, Bjarne Bogen

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Abstract:

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.

References

[1]	Pulendran B, Ahmed R (2011) Immunological mechanisms of vaccination. Nat Immunol 12: 509–517.
[2]	Grun JL, Maurer PH (1989) Different T helper cell subsets elicited in mice utilizing two different adjuvant vehicles: the role of endogenous interleukin 1 in proliferative responses. Cell Immunol 121: 134–145.
[3]	Pulendran B, Artis D (2012) New paradigms in type 2 immunity. Science 337: 431–435 337/6093/431 [pii];10.1126/science.1221064 [doi].
[4]	Rabin EM, Ohara J, Paul WE (1985) B-cell stimulatory factor 1 activates resting B cells. Proc Natl Acad Sci U S A 82: 2935–2939.
[5]	Coffman RL, Ohara J, Bond MW, Carty J, Zlotnik A, et al. (1986) B cell stimulatory factor-1 enhances the IgE response of lipopolysaccharide-activated B cells. J Immunol 136: 4538–4541.
[6]	Vitetta ES, Ohara J, Myers CD, Layton JE, Krammer PH, et al. (1985) Serological, biochemical, and functional identity of B cell-stimulatory factor 1 and B cell differentiation factor for IgG1. J Exp Med 162: 1726–1731.
[7]	Finkelman FD, Katona IM, Mosmann TR, Coffman RL (1988) IFN-gamma regulates the isotypes of Ig secreted during in vivo humoral immune responses. J Immunol 140: 1022–1027.
[8]	Baldridge JR, Crane RT (1999) Monophosphoryl lipid A (MPL) formulations for the next generation of vaccines. Methods 19: 103–107 10.1006/meth.1999.0834 [doi];S1046-2023(99)90834-4 [pii].
[9]	Glimcher LH, Murphy KM (2000) Lineage commitment in the immune system: the T helper lymphocyte grows up. Genes Dev 14: 1693–1711.
[10]	Kawamura H, Berzofsky JA (1986) Enhancement of antigenic potency in vitro and immunogenicity in vivo by coupling the antigen to anti-immunoglobulin. J Immunol 136: 58–65.
[11]	Snider DP, Segal DM (1987) Targeted antigen presentation using crosslinked antibody heteroaggregates. J Immunol 139: 1609–1616.
[12]	Casten LA, Pierce SK (1988) Receptor-mediated B cell antigen processing. Increased antigenicity of a globular protein covalently coupled to antibodies specific for B cell surface structures. J Immunol 140: 404–410.
[13]	Lees A, Morris SC, Thyphronitis G, Holmes JM, Inman JK, et al. (1990) Rapid stimulation of large specific antibody responses with conjugates of antigen and anti-IgD antibody. J Immunol 145: 3594–3600.
[14]	Baier G, Baier-Bitterlich G, Looney DJ, Altman A (1995) Immunogenic targeting of recombinant peptide vaccines to human antigen-presenting cells by chimeric anti-HLA-DR and anti-surface immunoglobulin D antibody Fab fragments in vitro. J Virol 69: 2357–2365.
[15]	Boyle JS, Brady JL, Lew AM (1998) Enhanced responses to a DNA vaccine encoding a fusion antigen that is directed to sites of immune induction. Nature 392: 408–411 10.1038/32932 [doi].
[16]	Lunde E, Munthe LA, Vabo A, Sandlie I, Bogen B (1999) Antibodies engineered with IgD specificity efficiently deliver integrated T-cell epitopes for antigen presentation by B cells. Nat Biotechnol 17: 670–675 10.1038/10883 [doi].
[17]	Biragyn A, Tani K, Grimm MC, Weeks S, Kwak LW (1999) Genetic fusion of chemokines to a self tumor antigen induces protective, T-cell dependent antitumor immunity. Nat Biotechnol 17: 253–258 10.1038/6995 [doi].
[18]	Biragyn A, Ruffini PA, Coscia M, Harvey LK, Neelapu SS, et al. (2004) Chemokine receptor-mediated delivery directs self-tumor antigen efficiently into the class II processing pathway in vitro and induces protective immunity in vivo. Blood 104: 1961–1969 10.1182/blood-2004-02-0637 [doi];2004-02-0637 [pii].
[19]	Wille-Reece U, Wu CY, Flynn BJ, Kedl RM, Seder RA (2005) Immunization with HIV-1 Gag protein conjugated to a TLR7/8 agonist results in the generation of HIV-1 Gag-specific Th1 and CD8+ T cell responses. J Immunol 174: 7676–7683 174/12/7676 [pii].
[20]	Fredriksen AB, Sandlie I, Bogen B (2006) DNA vaccines increase immunogenicity of idiotypic tumor antigen by targeting novel fusion proteins to antigen-presenting cells. Mol Ther 13: 776–785 S1525–0016(05)01701-6 [pii];10.1016/j.ymthe.2005.10.019 [doi].
[21]	Schiavo R, Baatar D, Olkhanud P, Indig FE, Restifo N, et al. (2006) Chemokine receptor targeting efficiently directs antigens to MHC class I pathways and elicits antigen-specific CD8+ T-cell responses. Blood 107: 4597–4605 2005-08-3207 [pii];10.1182/blood-2005-08-3207 [doi].
[22]	Fredriksen AB, Bogen B (2007) Chemokine-idiotype fusion DNA vaccines are potentiated by bivalency and xenogeneic sequences. Blood 110: 1797–1805 blood-2006-06-032938 [pii];10.1182/blood-2006-06-032938 [doi].
[23]	Schjetne KW, Fredriksen AB, Bogen B (2007) Delivery of antigen to CD40 induces protective immune responses against tumors. J Immunol 178: 4169–4176 178/7/4169 [pii].
[24]	Dudziak D, Kamphorst AO, Heidkamp GF, Buchholz VR, Trumpfheller C, et al. (2007) Differential antigen processing by dendritic cell subsets in vivo. Science 315: 107–111 315/5808/107 [pii];10.1126/science.1136080 [doi].
[25]	Ruffini PA, Grodeland G, Fredriksen AB, Bogen B (2010) Human chemokine MIP1alpha increases efficiency of targeted DNA fusion vaccines. Vaccine 29: 191–199 S0264-410X(10)01558-6 [pii];10.1016/j.vaccine.2010.10.057 [doi].
[26]	Treanor JJ, Taylor DN, Tussey L, Hay C, Nolan C, et al. (2010) Safety and immunogenicity of a recombinant hemagglutinin influenza-flagellin fusion vaccine (VAX125) in healthy young adults. Vaccine 28: 8268–8274 S0264-410X(10)01469-6 [pii];10.1016/j.vaccine.2010.10.009 [doi].
[27]	Grodeland G, Mjaaland S, Roux KH, Fredriksen AB, Bogen B (2013) DNA vaccine that target hemagglutinin to MHC II-molecules rapidly induces antibody-mediated protection against influenza. J Immunol 191: 3221–3231.
[28]	Staudt LM, Gerhard W (1983) Generation of antibody diversity in the immune response of BALB/c mice to influenza virus hemagglutinin. I. Significant variation in repertoire expression between individual mice. J Exp Med 157: 687–704.
[29]	Prat M, Gribaudo G, Comoglio PM, Cavallo G, Landolfo S (1984) Monoclonal antibodies against murine gamma interferon. Proc Natl Acad Sci U S A 81: 4515–4519.
[30]	Yang Z, Day YJ, Toufektsian MC, Xu Y, Ramos SI, et al. (2006) Myocardial infarct-sparing effect of adenosine A2A receptor activation is due to its action on CD4+ T lymphocytes. Circulation 114: 2056–2064 CIRCULATIONAHA.106.649244 [pii];10.1161/CIRCULATIONAHA.106.649244 [doi].
[31]	Andreasson K, Eriksson M, Tegerstedt K, Ramqvist T, Dalianis T (2010) CD4+ and CD8+ T cells can act separately in tumour rejection after immunization with murine pneumotropic virus chimeric Her2/neu virus-like particles. PLoS One 5: e11580 10.1371/journal.pone.0011580 [doi].
[32]	Tamura M, Kuwano K, Kurane I, Ennis FA (1998) Definition of amino acid residues on the epitope responsible for recognition by influenza A virus H1-specific, H2-specific, and H1- and H2-cross-reactive murine cytotoxic T-lymphocyte clones. J Virol 72: 9404–9406.
[33]	Hackett CJ, Dietzschold B, Gerhard W, Ghrist B, Knorr R, et al. (1983) Influenza virus site recognized by a murine helper T cell specific for H1 strains. Localization to a nine amino acid sequence in the hemagglutinin molecule. J Exp Med 158: 294–302.
[34]	Scott B, Liblau R, Degermann S, Marconi LA, Ogata L, et al. (1994) A role for non-MHC genetic polymorphism in susceptibility to spontaneous autoimmunity. Immunity 1: 73–83 1074-7613(94)90011-6 [pii].
[35]	Roos AK, Eriksson F, Walters DC, Pisa P, King AD (2009) Optimization of skin electroporation in mice to increase tolerability of DNA vaccine delivery to patients. Mol Ther 17: 1637–1642 mt2009120 [pii];10.1038/mt.2009.120 [doi].
[36]	Hickling JK, Jones KR, Friede M, Zehrung D, Chen D, et al. (2011) Intradermal delivery of vaccines: potential benefits and current challenges. Bull World Health Organ 89: 221–226 10.2471/BLT.10.079426 [doi].
[37]	Conway MA, Madrigal-Estebas L, McClean S, Brayden DJ, Mills KH (2001) Protection against Bordetella pertussis infection following parenteral or oral immunization with antigens entrapped in biodegradable particles: effect of formulation and route of immunization on induction of Th1 and Th2 cells. Vaccine 19: 1940–1950 S0264-410X(00)00433-3 [pii].
[38]	Apostolopoulos V, Pietersz GA, Loveland BE, Sandrin MS, McKenzie IF (1995) Oxidative/reductive conjugation of mannan to antigen selects for T1 or T2 immune responses. Proc Natl Acad Sci U S A 92: 10128–10132.
[39]	Chow YH, Chiang BL, Lee YL, Chi WK, Lin WC, et al. (1998) Development of Th1 and Th2 populations and the nature of immune responses to hepatitis B virus DNA vaccines can be modulated by codelivery of various cytokine genes. J Immunol 160: 1320–1329.
[40]	Ting JP, Trowsdale J (2002) Genetic control of MHC class II expression. Cell 109 SupplS21–S33 S0092867402006967 [pii].
[41]	Menten P, Wuyts A, Van DJ (2002) Macrophage inflammatory protein-1. Cytokine Growth Factor Rev 13: 455–481 S135961010200045X [pii].
[42]	Idoyaga J, Lubkin A, Fiorese C, Lahoud MH, Caminschi I, et al. (2011) Comparable T helper 1 (Th1) and CD8 T-cell immunity by targeting HIV gag p24 to CD8 dendritic cells within antibodies to Langerin, DEC205, and Clec9A. Proc Natl Acad Sci U S A 108: 2384–2389 1019547108 [pii];10.1073/pnas.1019547108 [doi].
[43]	Aihara H, Miyazaki J (1998) Gene transfer into muscle by electroporation in vivo. Nat Biotechnol 16: 867–870 10.1038/nbt0998-867 [doi].
[44]	Roos AK, Eriksson F, Walters DC, Pisa P, King AD (2009) Optimization of skin electroporation in mice to increase tolerability of DNA vaccine delivery to patients. Mol Ther 17: 1637–1642 mt2009120 [pii];10.1038/mt.2009.120 [doi].
[45]	Peng B, Zhao Y, Xu L, Xu Y (2007) Electric pulses applied prior to intramuscular DNA vaccination greatly improve the vaccine immunogenicity. Vaccine 25: 2064–2073 S0264-410X(06)01233-3 [pii];10.1016/j.vaccine.2006.11.042 [doi].
[46]	Roos AK, Eriksson F, Timmons JA, Gerhardt J, Nyman U, et al. (2009) Skin electroporation: effects on transgene expression, DNA persistence and local tissue environment. PLoS One 4: e7226 10.1371/journal.pone.0007226 [doi].
[47]	Cox NJ, Subbarao K (1999) Influenza. Lancet 354: 1277–1282 S0140-6736(99)01241-6 [pii];10.1016/S0140-6736(99)01241-6 [doi].
[48]	Mueller A, Kelly E, Strange PG (2002) Pathways for internalization and recycling of the chemokine receptor CCR5. Blood 99: 785–791.
[49]	McMichael AJ, Gotch FM, Noble GR, Beare PA (1983) Cytotoxic T-cell immunity to influenza. N Engl J Med 309: 13–17 10.1056/NEJM198307073090103 [doi].
[50]	Ulmer JB, Fu TM, Deck RR, Friedman A, Guan L, et al. (1998) Protective CD4+ and CD8+ T cells against influenza virus induced by vaccination with nucleoprotein DNA. J Virol 72: 5648–5653.
[51]	Epstein SL, Stack A, Misplon JA, Lo CY, Mostowski H, et al. (2000) Vaccination with DNA encoding internal proteins of influenza virus does not require CD8(+) cytotoxic T lymphocytes: either CD4(+) or CD8(+) T cells can promote survival and recovery after challenge. Int Immunol 12: 91–101.
[52]	Wilkinson TM, Li CK, Chui CS, Huang AK, Perkins M, et al. (2012) Preexisting influenza-specific CD4+ T cells correlate with disease protection against influenza challenge in humans. Nat Med 18: 274–280 nm.2612 [pii];10.1038/nm.2612 [doi].
[53]	Bennett SR, Carbone FR, Karamalis F, Miller JF, Heath WR (1997) Induction of a CD8+ cytotoxic T lymphocyte response by cross-priming requires cognate CD4+ T cell help. J Exp Med 186: 65–70.
[54]	Bender BS, Croghan T, Zhang L, Small PA Jr (1992) Transgenic mice lacking class I major histocompatibility complex-restricted T cells have delayed viral clearance and increased mortality after influenza virus challenge. J Exp Med 175: 1143–1145.
[55]	von Herrath MG, Yokoyama M, Dockter J, Oldstone MB, Whitton JL (1996) CD4-deficient mice have reduced levels of memory cytotoxic T lymphocytes after immunization and show diminished resistance to subsequent virus challenge. J Virol 70: 1072–1079.
[56]	Cardin RD, Brooks JW, Sarawar SR, Doherty PC (1996) Progressive loss of CD8+ T cell-mediated control of a gamma-herpesvirus in the absence of CD4+ T cells. J Exp Med 184: 863–871.

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