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Dendritic Cell Targeting Vaccines

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Vaccine Analysis: Strategies, Principles, and Control

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Abstract

Dendritic cells (DCs) are the most potent class of antigen presenting cells and are versatile regulators of antigen-specific immune responses. Because of their seminal role in adaptive immunity, DCs have been the subject of therapeutic applications, including the exploration and development of DC-based vaccines (Steinman and Pope 2002; Steinman and Banchereau 2007). To overcome inefficient systemic antigen delivery by conventional DC-based vaccines, where pathogens or pathogenic antigens are introduced to ex vivo cultured DCs, a novel in vivo and in situ DC-targeting strategy has been developed that employs a DC-receptor (DCR) antibody fused to target antigen and administered with adjuvant (Trumpfheller et al. 2012). To date, various DC-specific endocytic receptors have been tested with success in applying this novel approach in animal models and one clinical trial, including the DCRs DEC-205/CD205, DCIR2, langerin and Cle9A (Jiang et al. 1995; Dudziak et al. 2007; Caminschi et al. 2008). Using the ovalbumin (OVA) model antigen, this DC-targeting strategy demonstrated robust targeting efficacy as well as efficient systemic antigen delivery leading to strong T cell immunity. Based on this and other demonstrations of capability, the vaccine efficacy of DC-targeting strategy was further developed and tested in various viral, bacterial, and cancer disease model systems (Trumpfheller et al. 2006; Do et al. 2010; Wang et al. 2012). This chapter focuses on DEC-205/CD205 and DCIR2 DCR antibodies and prophylaxis against pneumonic plague as a principal case study in the development of improved DC-targeting vaccines. The efficacy of DC-targeting strategy is discussed with regard to: (1) breadth and strength of T cell immunity, (2) DC subsets-specific immune responses and DC subsets targeting, (3) mucosal immunity induction, and (4) protection data against virulent human pathogen. This chapter finishes with discussions of lessons learned in developing DC-targeting strategies against other disease models, and future directions for improvement of DC-targeting vaccines.

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Abbreviations

AIDS/HIV:

Acquired immune deficiency syndrome and human immunodeficiency virus disease

APCs:

Antigen presenting cells

BAL:

Bronchoalveolar lavage

CD40L:

CD40 ligand

CFA:

Complete freund’s adjuvant

CFSE:

Carboxyfluorescein succinimidyl ester

CFU:

Colony forming unit

CHO:

Chinese hamster ovary

CMI:

Cell-mediated immunity

CTL:

Cytotoxic T lymphocytes

DCs:

Dendritic cells

DCR:

DC-receptor

DC-SIGN/CD209:

Dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin

DEC-205/CD205:

Dendritic and epithelial cells 205 kDa

EBNA-1:

Nuclear antigen 1 of Epstein-Bar-Virus

EBV:

Epstein Bar Virus

EDE:

Glu-Asp-Glu

ELISA:

Enzyme-linked immunosorbent assay

ELISPOT:

Enzyme-linked immunosorbent spot assay

F1:

Capsular antigen fraction 1

FACS:

Fluorescence activated cell sorting

Fcγ:

Cell-surface receptors that bind the Fc portion of IgG

GLA:

Glucopyranosyl lipid A

GM-CSF:

Granular macrophage colony stimulating factor

HER2:

Human epidermal growth factor receptor

HPV:

Human papilloma virus

ICS:

Intracellular cytokine staining

IFN:

Interferon

I.M.:

Intramascular

I.N.:

Intranasal

I.P.:

Intraperitoneally

KLH:

Keyhole limpet hemocyanin

KO:

Knock-out

LcrV:

Low-calcium response virulence protein

LD50 :

Lethal dose, 50 %

LNs:

Lymph nodes

LPS:

Lipopolysaccharide

mAb:

Monoclonal antibody

MAdCAM:

Mucosal addressin cell adhesion molecule

MALP-2:

Macrophage-activating lipopeptide-2

MCM:

Monocyte-conditioned medium

MDA5:

Melanoma differentiation-associated protein 5

MMR:

Macrophage mannose receptor

Mo-DCs:

Monocyte-derived DCs

MPLA:

Monophosphoryl lipid A

NHP:

Nonhuman primates

NK:

Natural killer

NKT:

Natural killer T

NOG:

NOD/LtSz-scid IL2Rγnull

NOS2:

Nitric oxide synthase 2

NYVAC:

New York vaccinia virus

OVA:

Ovalbumin

PBMC:

Peripheral blood mononuclear cell

PGE2:

Prostaglandin E2

Pgm-:

Pigmentation negative strain

PHRI:

Public health research institute

Poly IC:

Polyinosinic: polycytidylic acid

Poly ICLC:

Poly IC with poly-L-lysine and carboxymethyl cellulose

S.C.:

Subcutaneously

SDS PAGE:

Sodium dodecyl sulfate polyacrylamide gel electrophoresis

STAT:

Signal transducer and activator of transcription

T3SS:

Type III secretion system

TAPs:

Transporters for antigen presentation

TLR:

Toll-like receptors

TNF:

Tumor necrosis factor

Treg:

Regulatory T cell

TT:

Tetanus toxoid

Y. pestis:

Yersinia pestis

Yops:

Y. pestis effector molecules

References

  • Akira S, Takeda K, Kaisho T (2001) Toll-like receptors: critical proteins linking innate and acquired immunity. Nat Immunol 2:675–680

    CAS  PubMed  Google Scholar 

  • Albert ML, Sauter B, Bhardwaj N (1998) Dendritic cells acquire antigen from apoptotic cells and induce class I-restricted CTLs. Nature 392:86–89

    CAS  PubMed  Google Scholar 

  • Alexopoulou L, Holt AC, Medzhitov R, Flavell RA (2001) Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3. Nature 413:732–738

    CAS  PubMed  Google Scholar 

  • Allan RS, Smith CM, Belz GT, van Lint AL, Wakim LM, Heath WR, Carbone FR (2003) Epidermal viral immunity induced by CD8alpha + dendritic cells but not by Langerhans cells. Science 301:1925–1928

    CAS  PubMed  Google Scholar 

  • Altieri DC (2003) Validating survivin as a cancer therapeutic target. Nat Rev Cancer 3:46–54

    CAS  PubMed  Google Scholar 

  • Anderson GW Jr, Leary SE, Williamson ED, Titball RW, Welkos SL, Worsham PL, Friedlander AM (1996) Recombinant V antigen protects mice against pneumonic and bubonic plague caused by F1-capsule-positive and -negative strains of Yersinia pestis. Infect Immun 64:4580–4585

    CAS  PubMed Central  PubMed  Google Scholar 

  • Andrews GP, Heath DG, Anderson GW Jr, Welkos SL, Friedlander AM (1996) Fraction 1 capsular antigen (F1) purification from Yersinia pestis CO92 and from an Escherichia coli recombinant strain and efficacy against lethal plague challenge. Infect Immun 64:2180–2187

    CAS  PubMed Central  PubMed  Google Scholar 

  • Argani P, Iacobuzio-Donahue C, Ryu B, Rosty C, Goggins M, Wilentz RE, Murugesan SR, Leach SD, Jaffee E, Yeo CJ, Cameron JL, Kern SE, Hruban RH (2001) Mesothelin is overexpressed in the vast majority of ductal adenocarcinomas of the pancreas: identification of a new pancreatic cancer marker by serial analysis of gene expression (SAGE). Clin Cancer Res 7:3862–3868

    CAS  PubMed  Google Scholar 

  • Baca-Estrada ME, Foldvari MM, Snider MM, Harding KK, Kournikakis BB, Babiuk LA, Griebel PP (2000) Intranasal immunization with liposome-formulated Yersinia pestis vaccine enhances mucosal immune responses. Vaccine 18:2203–2211

    CAS  PubMed  Google Scholar 

  • Bachem A, Guttler S, Hartung E, Ebstein F, Schaefer M, Tannert A, Salama A, Movassaghi K, Opitz C, Mages HW, Henn V, Kloetzel PM, Gurka S, Kroczek RA (2010) Superior antigen cross-presentation and XCR1 expression define human CD11c+CD141+ cells as homologues of mouse CD8+ dendritic cells. J Exp Med 207:1273–1281

    CAS  PubMed Central  PubMed  Google Scholar 

  • Baldwin SL, Shaverdian N, Goto Y, Duthie MS, Raman VS, Evers T, Mompoint F, Vedvick TS, Bertholet S, Coler RN, Reed SG (2009) Enhanced humoral and Type 1 cellular immune responses with Fluzone adjuvanted with a synthetic TLR4 agonist formulated in an emulsion. Vaccine 27:5956–5963

    CAS  PubMed  Google Scholar 

  • Banchereau J, Schuler-Thurner B, Palucka AK, Schuler G (2001) Dendritic cells as vectors for therapy. Cell 106:271–274

    CAS  PubMed  Google Scholar 

  • Banchereau J, Steinman RM (1998) Dendritic cells and the control of immunity. Nature 392:245–252

    CAS  PubMed  Google Scholar 

  • Bates JH, Irvin CG (2003) Measuring lung function in mice: the phenotyping uncertainty principle. J Appl Physiol 94:1297–1306

    PubMed  Google Scholar 

  • Bendelac A, Medzhitov R (2002) Adjuvants of immunity: harnessing innate immunity to promote adaptive immunity. J Exp Med 195:F19–F23

    CAS  PubMed Central  PubMed  Google Scholar 

  • Bera TK, Pastan I (2000) Mesothelin is not required for normal mouse development or reproduction. Mol Cell Biol 20:2902–2906

    CAS  PubMed Central  PubMed  Google Scholar 

  • Berger TG, Feuerstein B, Strasser E, Hirsch U, Schreiner D, Schuler G, Schuler-Thurner B (2002) Large-scale generation of mature monocyte-derived dendritic cells for clinical application in cell factories. J Immunol Methods 268:131–140

    CAS  PubMed  Google Scholar 

  • Bevan MJ (2004) Helping the CD8(+) T-cell response. Nat Rev Immunol 4:595–602

    CAS  PubMed  Google Scholar 

  • Blanc-Brude OP, Mesri M, Wall NR, Plescia J, Dohi T, Altieri DC (2003) Therapeutic targeting of the survivin pathway in cancer: initiation of mitochondrial apoptosis and suppression of tumor-associated angiogenesis. Clin Cancer Res 9:2683–2692

    CAS  PubMed  Google Scholar 

  • Bonifaz L, Bonnyay D, Mahnke K, Rivera M, Nussenzweig MC, Steinman RM (2002) Efficient targeting of protein antigen to the dendritic cell receptor DEC-205 in the steady state leads to antigen presentation on major histocompatibility complex class I products and peripheral CD8+ T cell tolerance. J Exp Med 196:1627–1638

    CAS  PubMed Central  PubMed  Google Scholar 

  • Bonifaz LC, Bonnyay DP, Charalambous A, Darguste DI, Fujii S, Soares H, Brimnes MK, Moltedo B, Moran TM, Steinman RM (2004) In vivo targeting of antigens to maturing dendritic cells via the DEC-205 receptor improves T cell vaccination. J Exp Med 199:815–824

    CAS  PubMed Central  PubMed  Google Scholar 

  • Bozzacco L, Trumpfheller C, Siegal FP, Mehandru S, Markowitz M, Carrington M, Nussenzweig MC, Piperno AG, Steinman RM (2007) DEC-205 receptor on dendritic cells mediates presentation of HIV gag protein to CD8+ T cells in a spectrum of human MHC I haplotypes. Proc Natl Acad Sci USA 104:1289–1294

    CAS  PubMed Central  PubMed  Google Scholar 

  • Brubaker RR (1991) The V antigen of yersiniae: an overview. Contrib Microbiol Immunol 12:127–133

    CAS  PubMed  Google Scholar 

  • Bubeck SS, Cantwell AM, Dube PH (2007) Delayed inflammatory response to primary pneumonic plague occurs in both outbred and inbred mice. Infect Immun 75:697–705

    CAS  PubMed Central  PubMed  Google Scholar 

  • Caminschi I, Proietto AI, Ahmet F, Kitsoulis S, Shin Teh J, Lo JC, Rizzitelli A, Wu L, Vremec D, van Dommelen SL, Campbell IK, Maraskovsky E, Braley H, Davey GM, Mottram P, van de Velde N, Jensen K, Lew AM, Wright MD, Heath WR, Shortman K, Lahoud MH (2008) The dendritic cell subtype-restricted C-type lectin Clec9A is a target for vaccine enhancement. Blood 112:3264–3273

    CAS  PubMed Central  PubMed  Google Scholar 

  • Caskey M, Lefebvre F, Filali-Mouhim A, Cameron MJ, Goulet JP, Haddad EK, Breton G, Trumpfheller C, Pollak S, Shimeliovich I, Duque-Alarcon A, Pan L, Nelkenbaum A, Salazar AM, Schlesinger SJ, Steinman RM, Sekaly RP (2011) Synthetic double-stranded RNA induces innate immune responses similar to a live viral vaccine in humans. J Exp Med 208:2357–2366

    CAS  PubMed Central  PubMed  Google Scholar 

  • Chang K, Pastan I (1996) Molecular cloning of mesothelin, a differentiation antigen present on mesothelium, mesotheliomas, and ovarian cancers. Proc Natl Acad Sci USA 93:136–140

    CAS  PubMed Central  PubMed  Google Scholar 

  • Charalambous A, Oks M, Nchinda G, Yamazaki S, Steinman RM (2006) Dendritic cell targeting of survivin protein in a xenogeneic form elicits strong CD4+ T cell immunity to mouse survivin. J Immunol 177:8410–8421

    CAS  PubMed  Google Scholar 

  • Cheong C, Choi JH, Vitale L, He LZ, Trumpfheller C, Bozzacco L, Do Y, Nchinda G, Park SH, Dandamudi DB, Shrestha E, Pack M, Lee HW, Keler T, Steinman RM, Park CG (2010) Improved cellular and humoral immune responses in vivo following targeting of HIV Gag to dendritic cells within human anti-human DEC205 monoclonal antibody. Blood 116:3828–3838

    CAS  PubMed Central  PubMed  Google Scholar 

  • Coler RN, Baldwin SL, Shaverdian N, Bertholet S, Reed SJ, Raman VS, Lu X, DeVos J, Hancock K, Katz JM, Vedvick TS, Duthie MS, Clegg CH, Van Hoeven N, Reed SG (2010) A synthetic adjuvant to enhance and expand immune responses to influenza vaccines. PLoS ONE 5:e13677

    PubMed Central  PubMed  Google Scholar 

  • Corbeil LB, Gogolewski RP, Kacskovics I, Nielsen KH, Corbeil RR, Morrill JL, Greenwood R, Butler JE (1997) Bovine IgG2a antibodies to Haemophilus somnus and allotype expression. Can J Vet Res 61:207–213

    CAS  PubMed Central  PubMed  Google Scholar 

  • Cyster JG (1999) Chemokines and the homing of dendritic cells to the T cell areas of lymphoid organs. J Exp Med 189:447–450

    CAS  PubMed Central  PubMed  Google Scholar 

  • Darrah PA, Patel DT, De Luca PM, Lindsay RW, Davey DF, Flynn BJ, Hoff ST, Andersen P, Reed SG, Morris SL, Roederer M, Seder RA (2007) Multifunctional TH1 cells define a correlate of vaccine-mediated protection against Leishmania major. Nat Med 13:843–850

    CAS  PubMed  Google Scholar 

  • Davis KJ, Fritz DL, Pitt ML, Welkos SL, Worsham PL, Friedlander AM (1996) Pathology of experimental pneumonic plague produced by fraction 1-positive and fraction 1-negative Yersinia pestis in African green monkeys (Cercopithecus aethiops). Arch Pathol Lab Med 120:156–163

    CAS  PubMed  Google Scholar 

  • Dela Cruz JS, Lau SY, Ramirez EM, De Giovanni C, Forni G, Morrison SL, Penichet ML (2003) Protein vaccination with the HER2/neu extracellular domain plus anti-HER2/neu antibody-cytokine fusion proteins induces a protective anti-HER2/neu immune response in mice. Vaccine 21:1317–1326

    CAS  PubMed  Google Scholar 

  • den Haan JM, Lehar SM, Bevan MJ (2000) CD8(+) but not CD8(−) dendritic cells cross-prime cytotoxic T cells in vivo. J Exp Med 192:1685–1696

    Google Scholar 

  • Disis ML, Calenoff E, McLaughlin G, Murphy AE, Chen W, Groner B, Jeschke M, Lydon N, McGlynn E, Livingston RB et al (1994) Existent T-cell and antibody immunity to HER-2/neu protein in patients with breast cancer. Cancer Res 54:16–20

    CAS  PubMed  Google Scholar 

  • Disis ML, Knutson KL, Schiffman K, Rinn K, McNeel DG (2000) Pre-existent immunity to the HER-2/neu oncogenic protein in patients with HER-2/neu overexpressing breast and ovarian cancer. Breast Cancer Res Treat 62:245–252

    CAS  PubMed  Google Scholar 

  • Do Y, Didierlaurent AM, Ryu S, Koh H, Park CG, Park S, Perlin DS, Powell BS, Steinman RM (2012) Induction of pulmonary mucosal immune responses with a protein vaccine targeted to the DEC-205/CD205 receptor. Vaccine 30:6359–6367

    CAS  PubMed Central  PubMed  Google Scholar 

  • Do Y, Koh H, Park CG, Dudziak D, Seo P, Mehandru S, Choi JH, Cheong C, Park S, Perlin DS, Powell BS, Steinman RM (2010) Targeting of LcrV virulence protein from Yersinia pestis to dendritic cells protects mice against pneumonic plague. Eur J Immunol 40:2791–2796

    CAS  PubMed  Google Scholar 

  • Do Y, Park CG, Kang YS, Park SH, Lynch RM, Lee H, Powell BS, Steinman RM (2008) Broad T cell immunity to the LcrV virulence protein is induced by targeted delivery to DEC-205/CD205-positive mouse dendritic cells. Eur J Immunol 38:20–29

    CAS  PubMed Central  PubMed  Google Scholar 

  • Du Y, Rosqvist R, Forsberg A (2002) Role of fraction 1 antigen of Yersinia pestis in inhibition of phagocytosis. Infect Immun 70:1453–1460

    CAS  PubMed Central  PubMed  Google Scholar 

  • Dubensky TW Jr, Reed SG (2010) Adjuvants for cancer vaccines. Semin Immunol 22:155–161

    CAS  PubMed  Google Scholar 

  • Dudziak D, Kamphorst AO, Heidkamp GF, Buchholz VR, Trumpfheller C, Yamazaki S, Cheong C, Liu K, Lee HW, Park CG, Steinman RM, Nussenzweig MC (2007) Differential antigen processing by dendritic cell subsets in vivo. Science 315:107–111

    CAS  PubMed  Google Scholar 

  • Dzionek A, Sohma Y, Nagafune J, Cella M, Colonna M, Facchetti F, Gunther G, Johnston I, Lanzavecchia A, Nagasaka T, Okada T, Vermi W, Winkels G, Yamamoto T, Zysk M, Yamaguchi Y, Schmitz J (2001) BDCA-2, a novel plasmacytoid dendritic cell-specific type II C-type lectin, mediates antigen capture and is a potent inhibitor of interferon alpha/beta induction. J Exp Med 194:1823–1834

    CAS  PubMed Central  PubMed  Google Scholar 

  • Elvin SJ, Williamson ED (2004) Stat 4 but not Stat 6 mediated immune mechanisms are essential in protection against plague. Microb Pathog 37:177–184

    CAS  PubMed  Google Scholar 

  • Emini EA, Koff WC (2004) AIDS/HIV. Developing an AIDS vaccine: need, uncertainty, hope. Science 304:1913–1914

    CAS  PubMed  Google Scholar 

  • Engering A, Geijtenbeek TB, van Vliet SJ, Wijers M, van Liempt E, Demaurex N, Lanzavecchia A, Fransen J, Figdor CG, Piguet V, van Kooyk Y (2002) The dendritic cell-specific adhesion receptor DC-SIGN internalizes antigen for presentation to T cells. J Immunol 168:2118–2126

    CAS  PubMed  Google Scholar 

  • Engering A, Pieters J (2001) Association of distinct tetraspanins with MHC class II molecules at different subcellular locations in human immature dendritic cells. Int Immunol 13:127–134

    CAS  PubMed  Google Scholar 

  • Eyles JE, Sharp GJ, Williamson ED, Spiers ID, Alpar HO (1998) Intra nasal administration of poly-lactic acid microsphere co-encapsulated Yersinia pestis subunits confers protection from pneumonic plague in the mouse. Vaccine 16:698–707

    CAS  PubMed  Google Scholar 

  • Eyles JE, Williamson ED, Spiers ID, Alpar HO (2000) Protection studies following bronchopulmonary and intramuscular immunisation with yersinia pestis F1 and V subunit vaccines coencapsulated in biodegradable microspheres: a comparison of efficacy. Vaccine 18:3266–3271

    CAS  PubMed  Google Scholar 

  • Flynn BJ, Kastenmuller K, Wille-Reece U, Tomaras GD, Alam M, Lindsay RW, Salazar AM, Perdiguero B, Gomez CE, Wagner R, Esteban M, Park CG, Trumpfheller C, Keler T, Pantaleo G, Steinman RM, Seder R (2011) Immunization with HIV Gag targeted to dendritic cells followed by recombinant New York vaccinia virus induces robust T-cell immunity in nonhuman primates. Proc Natl Acad Sci USA 108:7131–7136

    CAS  PubMed Central  PubMed  Google Scholar 

  • Fong L, Brockstedt D, Benike C, Wu L, Engleman EG (2001a) Dendritic cells injected via different routes induce immunity in cancer patients. J Immunol 166:4254–4259

    CAS  PubMed  Google Scholar 

  • Fong L, Hou Y, Rivas A, Benike C, Yuen A, Fisher GA, Davis MM, Engleman EG (2001b) Altered peptide ligand vaccination with Flt3 ligand expanded dendritic cells for tumor immunotherapy. Proc Natl Acad Sci U S A 98:8809–8814

    CAS  PubMed Central  PubMed  Google Scholar 

  • Fujii S, Liu K, Smith C, Bonito AJ, Steinman RM (2004) The linkage of innate to adaptive immunity via maturing dendritic cells in vivo requires CD40 ligation in addition to antigen presentation and CD80/86 costimulation. J Exp Med 199:1607–1618

    CAS  PubMed Central  PubMed  Google Scholar 

  • Gomez CE, Najera JL, Jimenez V, Bieler K, Wild J, Kostic L, Heidari S, Chen M, Frachette MJ, Pantaleo G, Wolf H, Liljestrom P, Wagner R, Esteban M (2007) Generation and immunogenicity of novel HIV/AIDS vaccine candidates targeting HIV-1 Env/Gag-Pol-Nef antigens of clade C. Vaccine 25:1969–1992

    CAS  PubMed  Google Scholar 

  • Granelli-Piperno A, Pritsker A, Pack M, Shimeliovich I, Arrighi JF, Park CG, Trumpfheller C, Piguet V, Moran TM, Steinman RM (2005) Dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin/CD209 is abundant on macrophages in the normal human lymph node and is not required for dendritic cell stimulation of the mixed leukocyte reaction. J Immunol 175:4265–4273

    CAS  PubMed Central  PubMed  Google Scholar 

  • Griffin KF, Conway BR, Alpar HO, Williamson ED (1998) Immune responses to V antigen of Yersinia pestis co-encapsulated with IFN-gamma: effect of dose and formulation. Vaccine 16:517–521

    CAS  PubMed  Google Scholar 

  • Grossman D, Kim PJ, Schechner JS, Altieri DC (2001) Inhibition of melanoma tumor growth in vivo by survivin targeting. Proc Natl Acad Sci USA 98:635–640

    CAS  PubMed Central  PubMed  Google Scholar 

  • Guo M, Gong S, Maric S, Misulovin Z, Pack M, Mahnke K, Nussenzweig MC, Steinman RM (2000) A monoclonal antibody to the DEC-205 endocytosis receptor on human dendritic cells. Hum Immunol 61:729–738

    CAS  PubMed  Google Scholar 

  • Gurer C, Strowig T, Brilot F, Pack M, Trumpfheller C, Arrey F, Park CG, Steinman RM, Munz C (2008) Targeting the nuclear antigen 1 of Epstein-Barr virus to the human endocytic receptor DEC-205 stimulates protective T-cell responses. Blood 112:1231–1239

    CAS  PubMed Central  PubMed  Google Scholar 

  • Harris NL, Watt V, Ronchese F, Le Gros G (2002) Differential T cell function and fate in lymph node and nonlymphoid tissues. J Exp Med 195:317–326

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hassan R, Ho M (2008) Mesothelin targeted cancer immunotherapy. Eur J Cancer 44:46–53

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hawiger D, Inaba K, Dorsett Y, Guo M, Mahnke K, Rivera M, Ravetch JV, Steinman RM, Nussenzweig MC (2001) Dendritic cells induce peripheral T cell unresponsiveness under steady state conditions in vivo. J Exp Med 194:769–779

    CAS  PubMed Central  PubMed  Google Scholar 

  • Heath DG, Anderson GW Jr, Mauro JM, Welkos SL, Andrews GP, Adamovicz J, Friedlander AM (1998) Protection against experimental bubonic and pneumonic plague by a recombinant capsular F1-V antigen fusion protein vaccine. Vaccine 16:1131–1137

    CAS  PubMed  Google Scholar 

  • Heath WR, Belz GT, Behrens GM, Smith CM, Forehan SP, Parish IA, Davey GM, Wilson NS, Carbone FR, Villadangos JA (2004) Cross-presentation, dendritic cell subsets, and the generation of immunity to cellular antigens. Immunol Rev 199:9–26

    CAS  PubMed  Google Scholar 

  • Hildner K, Edelson BT, Purtha WE, Diamond M, Matsushita H, Kohyama M, Calderon B, Schraml BU, Unanue ER, Diamond MS, Schreiber RD, Murphy TL, Murphy KM (2008) Batf3 deficiency reveals a critical role for CD8alpha+ dendritic cells in cytotoxic T cell immunity. Science 322:1097–1100

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hill J, Eyles JE, Elvin SJ, Healey GD, Lukaszewski RA, Titball RW (2006) Administration of antibody to the lung protects mice against pneumonic plague. Infect Immun 74:3068–3070

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ho M, Bera TK, Willingham MC, Onda M, Hassan R, FitzGerald D, Pastan I (2007) Mesothelin expression in human lung cancer. Clin Cancer Res 13:1571–1575

    CAS  PubMed  Google Scholar 

  • Honko AN, Sriranganathan N, Lees CJ, Mizel SB (2006) Flagellin is an effective adjuvant for immunization against lethal respiratory challenge with Yersinia pestis. Infect Immun 74:1113–1120

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hsu FJ, Benike C, Fagnoni F, Liles TM, Czerwinski D, Taidi B, Engleman EG, Levy R (1996) Vaccination of patients with B-cell lymphoma using autologous antigen-pulsed dendritic cells. Nat Med 2:52–58

    CAS  PubMed  Google Scholar 

  • Hynes NE, Stern DF (1994) The biology of erbB-2/neu/HER-2 and its role in cancer. Biochim Biophys Acta 1198:165–184

    PubMed  Google Scholar 

  • Ichinohe T, Kawaguchi A, Tamura S, Takahashi H, Sawa H, Ninomiya A, Imai M, Itamura S, Odagiri T, Tashiro M, Chiba J, Sata T, Kurata T, Hasegawa H (2007) Intranasal immunization with H5N1 vaccine plus Poly I:Poly C12U, a Toll-like receptor agonist, protects mice against homologous and heterologous virus challenge. Microbes Infect 9:1333–1340

    CAS  PubMed  Google Scholar 

  • Ichinohe T, Watanabe I, Ito S, Fujii H, Moriyama M, Tamura S, Takahashi H, Sawa H, Chiba J, Kurata T, Sata T, Hasegawa H (2005) Synthetic double-stranded RNA poly(I:C) combined with mucosal vaccine protects against influenza virus infection. J Virol 79:2910–2919

    CAS  PubMed Central  PubMed  Google Scholar 

  • Inglesby TV, Dennis DT, Henderson DA, Bartlett JG, Ascher MS, Eitzen E, Fine AD, Friedlander AM, Hauer J, Koerner JF, Layton M, McDade J, Osterholm MT, O’Toole T, Parker G, Perl TM, Russell PK, Schoch-Spana M, Tonat K (2000) Plague as a biological weapon: medical and public health management. Working Group Civilian Biodefense. Jama 283:2281–2290

    CAS  Google Scholar 

  • Islam A, Kageyama H, Takada N, Kawamoto T, Takayasu H, Isogai E, Ohira M, Hashizume K, Kobayashi H, Kaneko Y, Nakagawara A (2000) High expression of Survivin, mapped to 17q25, is significantly associated with poor prognostic factors and promotes cell survival in human neuroblastoma. Oncogene 19:617–623

    CAS  PubMed  Google Scholar 

  • Iyoda T, Shimoyama S, Liu K, Omatsu Y, Akiyama Y, Maeda Y, Takahara K, Steinman RM, Inaba K (2002) The CD8+ dendritic cell subset selectively endocytoses dying cells in culture and in vivo. J Exp Med 195:1289–1302

    CAS  PubMed Central  PubMed  Google Scholar 

  • Jiang W, Swiggard WJ, Heufler C, Peng M, Mirza A, Steinman RM, Nussenzweig MC (1995) The receptor DEC-205 expressed by dendritic cells and thymic epithelial cells is involved in antigen processing. Nature 375:151–155

    CAS  PubMed  Google Scholar 

  • Jones T, Adamovicz JJ, Cyr SL, Bolt CR, Bellerose N, Pitt LM, Lowell GH, Burt DS (2006) Intranasal Protollin/F1-V vaccine elicits respiratory and serum antibody responses and protects mice against lethal aerosolized plague infection. Vaccine 24:1625–1632

    CAS  PubMed  Google Scholar 

  • Jongbloed SL, Kassianos AJ, McDonald KJ, Clark GJ, Ju X, Angel CE, Chen CJ, Dunbar PR, Wadley RB, Jeet V, Vulink AJ, Hart DN, Radford KJ (2010) Human CD141+ (BDCA-3)+ dendritic cells (DCs) represent a unique myeloid DC subset that cross-presents necrotic cell antigens. J Exp Med 207:1247–1260

    CAS  PubMed Central  PubMed  Google Scholar 

  • Jonuleit H, Giesecke-Tuettenberg A, Tuting T, Thurner-Schuler B, Stuge TB, Paragnik L, Kandemir A, Lee PP, Schuler G, Knop J, Enk AH (2001) A comparison of two types of dendritic cell as adjuvants for the induction of melanoma-specific T-cell responses in humans following intranodal injection. Int J Cancer 93:243–251

    CAS  PubMed  Google Scholar 

  • Jung S, Unutmaz D, Wong P, Sano G, De los Santos K, Sparwasser T, Wu S, Vuthoori S, Ko K, Zavala F, Pamer EG, Littman DR, Lang RA (2002) In vivo depletion of CD11c+ dendritic cells abrogates priming of CD8+ T cells by exogenous cell-associated antigens. Immunity 17: 211–220

    Google Scholar 

  • Kamath AT, Henri S, Battye F, Tough DF, Shortman K (2002) Developmental kinetics and lifespan of dendritic cells in mouse lymphoid organs. Blood 100:1734–1741

    CAS  PubMed  Google Scholar 

  • Kamath AT, Pooley J, O’Keeffe MA, Vremec D, Zhan Y, Lew AM, D’Amico A, Wu L, Tough DF, Shortman K (2000) The development, maturation, and turnover rate of mouse spleen dendritic cell populations. J Immunol 165:6762–6770

    CAS  PubMed  Google Scholar 

  • Kawai T, Akira S (2007) Antiviral signaling through pattern recognition receptors. J Biochem 141:137–145

    CAS  PubMed  Google Scholar 

  • Kim YS, Kim YJ, Lee JM, Han SH, Ko HJ, Park HJ, Pereboev A, Nguyen HH, Kang CY (2010) CD40-targeted recombinant adenovirus significantly enhances the efficacy of antitumor vaccines based on dendritic cells and B cells. Hum Gene Ther 21:1697–1706

    CAS  PubMed  Google Scholar 

  • Krown SE, Kerr D, Stewart WE 2nd, Field AK, Oettgen HF (1985) Phase I trials of poly(I, C) complexes in advanced cancer. J Biol Response Mod 4:640–649

    CAS  PubMed  Google Scholar 

  • Lampkin BC, Levine AS, Levy H, Krivit W, Hammond D (1985) Phase II trial of a complex polyriboinosinic-polyribocytidylic acid with poly-L-lysine and carboxymethyl cellulose in the treatment of children with acute leukemia and neuroblastoma: a report from the Children’s Cancer Study Group. Cancer Res 45:5904–5909

    CAS  PubMed  Google Scholar 

  • Lathem WW, Crosby SD, Miller VL, Goldman WE (2005) Progression of primary pneumonic plague: a mouse model of infection, pathology, and bacterial transcriptional activity. Proc Natl Acad Sci USA 102:17786–17791

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lefrancois L, Puddington L (2006) Intestinal and pulmonary mucosal T cells: local heroes fight to maintain the status quo. Annu Rev Immunol 24:681–704

    CAS  PubMed  Google Scholar 

  • Levy HB, London W, Fuccillo DA, Baron S, Rice J (1976) Prophylactic control of simian hemorrhagic fever in monkeys by an interferon inducer, polyriboinosinic-polyribocytidylic acid-poly-L-lysine. J Infect Dis 133(Suppl):A256–A259

    PubMed  Google Scholar 

  • Li F, Ambrosini G, Chu EY, Plescia J, Tognin S, Marchisio PC, Altieri DC (1998) Control of apoptosis and mitotic spindle checkpoint by survivin. Nature 396:580–584

    CAS  PubMed  Google Scholar 

  • Lichterfeld M, Kaufmann DE, Yu XG, Mui SK, Addo MM, Johnston MN, Cohen D, Robbins GK, Pae E, Alter G, Wurcel A, Stone D, Rosenberg ES, Walker BD, Altfeld M (2004) Loss of HIV-1-specific CD8+ T cell proliferation after acute HIV-1 infection and restoration by vaccine-induced HIV-1-specific CD4+ T cells. J Exp Med 200:701–712

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lin JS, Kummer LW, Szaba FM, Smiley ST (2011a) IL-17 contributes to cell-mediated defense against pulmonary Yersinia pestis infection. J Immunol 186:1675–1684

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lin JS, Park S, Adamovicz JJ, Hill J, Bliska JB, Cote CK, Perlin DS, Amemiya K, Smiley ST (2010) TNFalpha and IFNgamma contribute to F1/LcrV-targeted immune defense in mouse models of fully virulent pneumonic plague. Vaccine 29:357–362

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lin JS, Szaba FM, Kummer LW, Chromy BA, Smiley ST (2011b) Yersinia pestis YopE contains a dominant CD8 T cell epitope that confers protection in a mouse model of pneumonic plague. J Immunol 187:897–904

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lin ML, Zhan Y, Proietto AI, Prato S, Wu L, Heath WR, Villadangos JA, Lew AM (2008) Selective suicide of cross-presenting CD8+ dendritic cells by cytochrome c injection shows functional heterogeneity within this subset. Proc Natl Acad Sci USA 105:3029–3034

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lindenstrom T, Agger EM, Korsholm KS, Darrah PA, Aagaard C, Seder RA, Rosenkrands I, Andersen P (2009) Tuberculosis subunit vaccination provides long-term protective immunity characterized by multifunctional CD4 memory T cells. J Immunol 182:8047–8055

    CAS  PubMed  Google Scholar 

  • Liu J, O’Brien KL, Lynch DM, Simmons NL, La Porte A, Riggs AM, Abbink P, Coffey RT, Grandpre LE, Seaman MS, Landucci G, Forthal DN, Montefiori DC, Carville A, Mansfield KG, Havenga MJ, Pau MG, Goudsmit J, Barouch DH (2009) Immune control of an SIV challenge by a T-cell-based vaccine in rhesus monkeys. Nature 457:87–91

    CAS  PubMed Central  PubMed  Google Scholar 

  • Longhi MP, Trumpfheller C, Idoyaga J, Caskey M, Matos I, Kluger C, Salazar AM, Colonna M, Steinman RM (2009) Dendritic cells require a systemic type I interferon response to mature and induce CD4+ Th1 immunity with poly IC as adjuvant. J Exp Med 206:1589–1602

    CAS  PubMed Central  PubMed  Google Scholar 

  • Mahnke K, Guo M, Lee S, Sepulveda H, Swain SL, Nussenzweig M, Steinman RM (2000) The dendritic cell receptor for endocytosis, DEC-205, can recycle and enhance antigen presentation via major histocompatibility complex class II-positive lysosomal compartments. J Cell Biol 151:673–684

    CAS  PubMed Central  PubMed  Google Scholar 

  • Maldonado-Lopez R, De Smedt T, Michel P, Godfroid J, Pajak B, Heirman C, Thielemans K, Leo O, Urbain J, Moser M (1999) CD8alpha+ and CD8alpha- subclasses of dendritic cells direct the development of distinct T helper cells in vivo. J Exp Med 189:587–592

    CAS  PubMed Central  PubMed  Google Scholar 

  • Marketon MM, DePaolo RW, DeBord KL, Jabri B, Schneewind O (2005) Plague bacteria target immune cells during infection. Science 309:1739–1741

    CAS  PubMed Central  PubMed  Google Scholar 

  • Mata-Haro V, Cekic C, Martin M, Chilton PM, Casella CR, Mitchell TC (2007) The vaccine adjuvant monophosphoryl lipid a as a TRIF-biased agonist of TLR4. Science 316:1628–1632

    CAS  PubMed  Google Scholar 

  • McIlroy D, Troadec C, Grassi F, Samri A, Barrou B, Autran B, Debre P, Feuillard J, Hosmalin A (2001) Investigation of human spleen dendritic cell phenotype and distribution reveals evidence of in vivo activation in a subset of organ donors. Blood 97:3470–3477

    CAS  PubMed  Google Scholar 

  • Medzhitov R (2001) Toll-like receptors and innate immunity. Nat Rev Immunol 1:135–145

    CAS  PubMed  Google Scholar 

  • Mellman I, Steinman RM (2001) Dendritic cells: specialized and regulated antigen processing machines. Cell 106:255–258

    CAS  PubMed  Google Scholar 

  • Mestas J, Hughes CC (2004) Of mice and not men: differences between mouse and human immunology. J Immunol 172:2731–2738

    CAS  PubMed  Google Scholar 

  • Meyer KF (1970) Effectiveness of live or killed plague vaccines in man. Bull World Health Organ 42:653–666

    CAS  PubMed Central  PubMed  Google Scholar 

  • Meyer KF, Hightower JA, McCrumb FR (1974) Plague immunization. VI. Vaccination with the fraction i antigen of Yersinia pestis. J Infect Dis 129(Suppl):S41–S45

    PubMed  Google Scholar 

  • Mills KH, Ryan M, Ryan E, Mahon BP (1998) A murine model in which protection correlates with pertussis vaccine efficacy in children reveals complementary roles for humoral and cell-mediated immunity in protection against Bordetella pertussis. Infect Immun 66:594–602

    CAS  PubMed Central  PubMed  Google Scholar 

  • Nakajima R, Brubaker RR (1993) Association between virulence of Yersinia pestis and suppression of gamma interferon and tumor necrosis factor alpha. Infect Immun 61:23–31

    CAS  PubMed Central  PubMed  Google Scholar 

  • Niess JH, Brand S, Gu X, Landsman L, Jung S, McCormick BA, Vyas JM, Boes M, Ploegh HL, Fox JG, Littman DR, Reinecker HC (2005) CX3CR1-mediated dendritic cell access to the intestinal lumen and bacterial clearance. Science 307:254–258

    CAS  PubMed  Google Scholar 

  • Nordlund JJ, Wolff SM, Levy HB (1970) Inhibition of biologic activity of poly I: poly C by human plasma. Proc Soc Exp Biol Med 133:439–444

    CAS  PubMed  Google Scholar 

  • Novitsky V, Gilbert P, Peter T, McLane MF, Gaolekwe S, Rybak N, Thior I, Ndung’u T, Marlink R, Lee TH, Essex M (2003) Association between virus-specific T-cell responses and plasma viral load in human immunodeficiency virus type 1 subtype C infection. J Virol 77:882–890

    CAS  PubMed Central  PubMed  Google Scholar 

  • Okada H, Bakal C, Shahinian A, Elia A, Wakeham A, Suh WK, Duncan GS, Ciofani M, Rottapel R, Zuniga-Pflucker JC, Mak TW (2004) Survivin loss in thymocytes triggers p53-mediated growth arrest and p53-independent cell death. J Exp Med 199:399–410

    CAS  PubMed Central  PubMed  Google Scholar 

  • Overheim K, Lemoine S, Gallegos K, Fisher I, Monier A, Schneider C, Valderas M, Wilder J, Russell R, Sherwood R, Leclaire R (2012a) Increased dose of recombinant F1/V plague vaccine results in increased survival in plague-challenged cynomologus macaques. In: ASM biodefense and emerging diseases research meeting, Washington, DC

    Google Scholar 

  • Overheim K, Lemoine S, Gallegos K, Fisher I, Monier A, Schneider C, Valderas M, Wilder J, Russell R, Sherwood R, Leclaire R (2012b) Increased protection of african green monkeys vaccinated with increasing doses of a recombinant F1/V plague vaccine. In: ASM Biodefense and Emerging Diseases research meeting, Washington, DC

    Google Scholar 

  • Pack M, Trumpfheller C, Thomas D, Park CG, Granelli-Piperno A, Munz C, Steinman RM (2008) DEC-205/CD205+ dendritic cells are abundant in the white pulp of the human spleen, including the border region between the red and white pulp. Immunology 123:438–446

    CAS  PubMed Central  PubMed  Google Scholar 

  • Palucka K, Banchereau J, Mellman I (2010) Designing vaccines based on biology of human dendritic cell subsets. Immunity 33:464–478

    CAS  PubMed Central  PubMed  Google Scholar 

  • Pamer E, Cresswell P (1998) Mechanisms of MHC class I–restricted antigen processing. Annu Rev Immunol 16:323–358

    CAS  PubMed  Google Scholar 

  • Pantel A, Cheong C, Dandamudi D, Shrestha E, Mehandru S, Brane L, Ruane D, Teixeira A, Bozzacco L, Steinman RM, Longhi MP (2012) A new synthetic TLR4 agonist, GLA, allows dendritic cells targeted with antigen to elicit Th1 T-cell immunity in vivo. Eur J Immunol 42:101–109

    CAS  PubMed Central  PubMed  Google Scholar 

  • Parent MA, Berggren KN, Kummer LW, Wilhelm LB, Szaba FM, Mullarky IK, Smiley ST (2005) Cell-mediated protection against pulmonary Yersinia pestis infection. Infect Immun 73:7304–7310

    CAS  PubMed Central  PubMed  Google Scholar 

  • Parent MA, Wilhelm LB, Kummer LW, Szaba FM, Mullarky IK, Smiley ST (2006) Gamma interferon, tumor necrosis factor alpha, and nitric oxide synthase 2, key elements of cellular immunity, perform critical protective functions during humoral defense against lethal pulmonary Yersinia pestis infection. Infect Immun 74:3381–3386

    CAS  PubMed Central  PubMed  Google Scholar 

  • Partidos CD, Hoebeke J, Moreau E, Chaloin O, Tunis M, Belliard G, Briand JP, Desgranges C, Muller S (2005) The binding affinity of double-stranded RNA motifs to HIV-1 Tat protein affects transactivation and the neutralizing capacity of anti-Tat antibodies elicited after intranasal immunization. Eur J Immunol 35:1521–1529

    CAS  PubMed  Google Scholar 

  • Perry RD, Fetherston JD (1997) Yersinia pestis–etiologic agent of plague. Clin Microbiol Rev 10:35–66

    CAS  PubMed Central  PubMed  Google Scholar 

  • Pitt ML (2004) Animal models and correlates of protection for plague vaccines workshop, Gaithersburg, MD. http://www.fda.gov/cber/minutes/workshop-min.htm

  • Poulin LF, Salio M, Griessinger E, Anjos-Afonso F, Craciun L, Chen JL, Keller AM, Joffre O, Zelenay S, Nye E, Le Moine A, Faure F, Donckier V, Sancho D, Cerundolo V, Bonnet D, Reis e Sousa C (2010) Characterization of human DNGR-1+BDCA3+ leukocytes as putative equivalents of mouse CD8alpha+ dendritic cells. J Exp Med 207:1261–1271

    CAS  PubMed Central  PubMed  Google Scholar 

  • Powell BS, Andrews GP, Enama JT, Jendrek S, Bolt C, Worsham P, Pullen JK, Ribot W, Hines H, Smith L, Heath DG, Adamovicz JJ (2005) Design and testing for a nontagged F1-V fusion protein as vaccine antigen against bubonic and pneumonic plague. Biotechnol Prog 21:1490–1510

    CAS  PubMed  Google Scholar 

  • Pulendran B, Smith JL, Caspary G, Brasel K, Pettit D, Maraskovsky E, Maliszewski CR (1999) Distinct dendritic cell subsets differentially regulate the class of immune response in vivo. Proc Natl Acad Sci USA 96:1036–1041

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ramamurthi KS, Schneewind O (2002) Type iii protein secretion in yersinia species. Annu Rev Cell Dev Biol 18:107–133

    CAS  PubMed  Google Scholar 

  • Randolph GJ, Angeli V, Swartz MA (2005) Dendritic-cell trafficking to lymph nodes through lymphatic vessels. Nat Rev Immunol 5:617–628

    CAS  PubMed  Google Scholar 

  • Reed DS, Martinez MJ (2006) Respiratory immunity is an important component of protection elicited by subunit vaccination against pneumonic plague. Vaccine 24:2283–2289

    CAS  PubMed  Google Scholar 

  • Regnault A, Lankar D, Lacabanne V, Rodriguez A, Thery C, Rescigno M, Saito T, Verbeek S, Bonnerot C, Ricciardi-Castagnoli P, Amigorena S (1999) Fcgamma receptor-mediated induction of dendritic cell maturation and major histocompatibility complex class I-restricted antigen presentation after immune complex internalization. J Exp Med 189:371–380

    CAS  PubMed Central  PubMed  Google Scholar 

  • Reis e Sousa C (2006) Dendritic cells in a mature age. Nat Rev Immunol 6:476–483

    CAS  PubMed  Google Scholar 

  • Rescigno M, Urbano M, Valzasina B, Francolini M, Rotta G, Bonasio R, Granucci F, Kraehenbuhl JP, Ricciardi-Castagnoli P (2001) Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria. Nat Immunol 2:361–367

    CAS  PubMed  Google Scholar 

  • Ridgway D (2003) The first 1000 dendritic cell vaccinees. Cancer Invest 21:873–886

    PubMed  Google Scholar 

  • Rosenberg ES, Billingsley JM, Caliendo AM, Boswell SL, Sax PE, Kalams SA, Walker BD (1997) Vigorous HIV-1-specific CD4+ T cell responses associated with control of viremia. Science 278:1447–1450

    CAS  PubMed  Google Scholar 

  • Salazar AM, Levy HB, Ondra S, Kende M, Scherokman B, Brown D, Mena H, Martin N, Schwab K, Donovan D, Dougherty D, Pulliam M, Ippolito M, Graves M, Brown H, Ommaya A (1996) Long-term treatment of malignant gliomas with intramuscularly administered polyinosinic-polycytidylic acid stabilized with polylysine and carboxymethylcellulose: an open pilot study. Neurosurgery 38: 1096–1103 (Discussion 1103–1094)

    Google Scholar 

  • Sallusto F, Cella M, Danieli C, Lanzavecchia A (1995) Dendritic cells use macropinocytosis and the mannose receptor to concentrate macromolecules in the major histocompatibility complex class II compartment: downregulation by cytokines and bacterial products. J Exp Med 182:389–400

    CAS  PubMed  Google Scholar 

  • Schmidt A, Rollinghoff M, Beuscher HU (1999) Suppression of TNF by V antigen of Yersinia spp. involves activated T cells. Eur J Immunol 29:1149–1157

    CAS  PubMed  Google Scholar 

  • Schnorrer P, Behrens GM, Wilson NS, Pooley JL, Smith CM, El-Sukkari D, Davey G, Kupresanin F, Li M, Maraskovsky E, Belz GT, Carbone FR, Shortman K, Heath WR, Villadangos JA (2006) The dominant role of CD8+ dendritic cells in cross-presentation is not dictated by antigen capture. Proc Natl Acad Sci USA 103:10729–10734

    CAS  PubMed Central  PubMed  Google Scholar 

  • Schuler-Thurner B, Schultz ES, Berger TG, Weinlich G, Ebner S, Woerl P, Bender A, Feuerstein B, Fritsch PO, Romani N, Schuler G (2002) Rapid induction of tumor-specific type 1 T helper cells in metastatic melanoma patients by vaccination with mature, cryopreserved, peptide-loaded monocyte-derived dendritic cells. J Exp Med 195:1279–1288

    CAS  PubMed Central  PubMed  Google Scholar 

  • Schuler G, Schuler-Thurner B, Steinman RM (2003) The use of dendritic cells in cancer immunotherapy. Curr Opin Immunol 15:138–147

    CAS  PubMed  Google Scholar 

  • Segura E, Albiston AL, Wicks IP, Chai SY, Villadangos JA (2009) Different cross-presentation pathways in steady-state and inflammatory dendritic cells. Proc Natl Acad Sci USA 106:20377–20381

    CAS  PubMed Central  PubMed  Google Scholar 

  • Shortman K, Liu YJ (2002) Mouse and human dendritic cell subtypes. Nat Rev Immunol 2:151–161

    CAS  PubMed  Google Scholar 

  • Shortman K, Naik SH (2007) Steady-state and inflammatory dendritic-cell development. Nat Rev Immunol 7:19–30

    CAS  PubMed  Google Scholar 

  • Sing A, Rost D, Tvardovskaia N, Roggenkamp A, Wiedemann A, Kirschning CJ, Aepfelbacher M, Heesemann J (2002) Yersinia V-antigen exploits toll-like receptor 2 and CD14 for interleukin 10-mediated immunosuppression. J Exp Med 196:1017–1024

    CAS  PubMed Central  PubMed  Google Scholar 

  • Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL (1987) Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235:177–182

    CAS  PubMed  Google Scholar 

  • Sloots A, Mastini C, Rohrbach F, Weth R, Curcio C, Burkhardt U, Jager E, Forni G, Cavallo F, Wels WS (2008) DNA vaccines targeting tumor antigens to B7 molecules on antigen-presenting cells induce protective antitumor immunity and delay onset of HER-2/Neu-driven mammary carcinoma. Clin Cancer Res 14:6933–6943

    CAS  PubMed  Google Scholar 

  • Stahl-Hennig C, Eisenblatter M, Jasny E, Rzehak T, Tenner-Racz K, Trumpfheller C, Salazar AM, Uberla K, Nieto K, Kleinschmidt J, Schulte R, Gissmann L, Muller M, Sacher A, Racz P, Steinman RM, Uguccioni M, Ignatius R (2009) Synthetic double-stranded RNAs are adjuvants for the induction of T helper 1 and humoral immune responses to human papillomavirus in rhesus macaques. PLoS Pathog 5:e1000373

    PubMed Central  PubMed  Google Scholar 

  • Steinhagen F, Kinjo T, Bode C, Klinman DM (2011) TLR-based immune adjuvants. Vaccine 29:3341–3355

    CAS  PubMed Central  PubMed  Google Scholar 

  • Steinman RM (2007) Dendritic cells: understanding immunogenicity. Eur J Immunol 37(Suppl 1):S53–S60

    CAS  PubMed  Google Scholar 

  • Steinman RM, Banchereau J (2007) Taking dendritic cells into medicine. Nature 449:419–426

    CAS  PubMed  Google Scholar 

  • Steinman RM, Dhodapkar M (2001) Active immunization against cancer with dendritic cells: the near future. Int J Cancer 94:459–473

    CAS  PubMed  Google Scholar 

  • Steinman RM, Pope M (2002) Exploiting dendritic cells to improve vaccine efficacy. J Clin Invest 109:1519–1526

    CAS  PubMed Central  PubMed  Google Scholar 

  • Stephen EL, Sammons ML, Pannier WL, Baron S, Spertzel RO, Levy HB (1977) Effect of a nuclease-resistant derivative of polyriboinosinic-polyribocytidylic acid complex on yellow fever in rhesus monkeys (Macaca mulatta). J Infect Dis 136:122–126

    CAS  PubMed  Google Scholar 

  • Stevenson HC, Abrams PG, Schoenberger CS, Smalley RB, Herberman RB, Foon KA (1985) A phase I evaluation of poly(I, C)-LC in cancer patients. J Biol Response Mod 4:650–655

    CAS  PubMed  Google Scholar 

  • Tamm I, Wang Y, Sausville E, Scudiero DA, Vigna N, Oltersdorf T, Reed JC (1998) IAP-family protein survivin inhibits caspase activity and apoptosis induced by Fas (CD95), Bax, caspases, and anticancer drugs. Cancer Res 58:5315–5320

    CAS  PubMed  Google Scholar 

  • Taylor P, Gerder M, Moros Z, Feldmann M (1996) Humoral and cellular responses raised against the human HER2 oncoprotein are cross-reactive with the homologous product of the new proto-oncogene, but do not protect rats against B104 tumors expressing mutated neu. Cancer Immunol Immunother 42:179–184

    CAS  PubMed  Google Scholar 

  • Thomann JS, Heurtault B, Weidner S, Braye M, Beyrath J, Fournel S, Schuber F, Frisch B (2011) Antitumor activity of liposomal ErbB2/HER2 epitope peptide-based vaccine constructs incorporating TLR agonists and mannose receptor targeting. Biomaterials 32:4574–4583

    CAS  PubMed  Google Scholar 

  • Thomas AM, Santarsiero LM, Lutz ER, Armstrong TD, Chen YC, Huang LQ, Laheru DA, Goggins M, Hruban RH, Jaffee EM (2004) Mesothelin-specific CD8(+) T cell responses provide evidence of in vivo cross-priming by antigen-presenting cells in vaccinated pancreatic cancer patients. J Exp Med 200:297–306

    CAS  PubMed Central  PubMed  Google Scholar 

  • Thompson KA, Strayer DR, Salvato PD, Thompson CE, Klimas N, Molavi A, Hamill AK, Zheng Z, Ventura D, Carter WA (1996) Results of a double-blind placebo-controlled study of the double-stranded RNA drug polyI:polyC12U in the treatment of HIV infection. Eur J Clin Microbiol Infect Dis 15:580–587

    CAS  PubMed  Google Scholar 

  • Trombetta ES, Mellman I (2005) Cell biology of antigen processing in vitro and in vivo. Annu Rev Immunol 23:975–1028

    CAS  PubMed  Google Scholar 

  • Trumpfheller C, Finke JS, Lopez CB, Moran TM, Moltedo B, Soares H, Huang Y, Schlesinger SJ, Park CG, Nussenzweig MC, Granelli-Piperno A, Steinman RM (2006) Intensified and protective CD4+ T cell immunity in mice with anti-dendritic cell HIV gag fusion antibody vaccine. J Exp Med 203:607–617

    CAS  PubMed Central  PubMed  Google Scholar 

  • Trumpfheller C, Longhi MP, Caskey M, Idoyaga J, Bozzacco L, Keler T, Schlesinger SJ, Steinman RM (2012) Dendritic cell-targeted protein vaccines: a novel approach to induce T-cell immunity. J Intern Med 271:183–192

    CAS  PubMed Central  PubMed  Google Scholar 

  • Trumpfheller C, Caskey M, Nchinda G, Longhi MP, Mizenina O, Huang Y, Schlesinger SJ, Colonna M, Steinman RM (2008) The microbial mimic polyIC induces durable and protective CD4+ T cell immunity together with a dendritic cell targeted vaccine. In: Proc Nat Acad Sci.USA (In Press)

    Google Scholar 

  • Turley SJ, Inaba K, Garrett WS, Ebersold M, Unternaehrer J, Steinman RM, Mellman I (2000) Transport of peptide-MHC class II complexes in developing dendritic cells. Science 288:522–527

    CAS  PubMed  Google Scholar 

  • Valladeau J, Ravel O, Dezutter-Dambuyant C, Moore K, Kleijmeer M, Liu Y, Duvert-Frances V, Vincent C, Schmitt D, Davoust J, Caux C, Lebecque S, Saeland S (2000) Langerin, a novel C-type lectin specific to Langerhans cells, is an endocytic receptor that induces the formation of Birbeck granules. Immunity 12:71–81

    CAS  PubMed  Google Scholar 

  • Villadangos JA, Shortman K (2010) Found in translation: the human equivalent of mouse CD8+ dendritic cells. J Exp Med 207:1131–1134

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wang B, Kuroiwa JM, He LZ, Charalambous A, Keler T, Steinman RM (2009) The human cancer antigen mesothelin is more efficiently presented to the mouse immune system when targeted to the DEC-205/CD205 receptor on dendritic cells. Ann NY Acad Sci 1174:6–17

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wang B, Zaidi N, He LZ, Zhang L, Kuroiwa JM, Keler T, Steinman RM (2012) Targeting of the non-mutated tumor antigen HER2/neu to mature dendritic cells induces an integrated immune response that protects against breast cancer in mice. Breast Cancer Res 14:R39

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wei H, Wang S, Zhang D, Hou S, Qian W, Li B, Guo H, Kou G, He J, Wang H, Guo Y (2009) Targeted delivery of tumor antigens to activated dendritic cells via CD11c molecules induces potent antitumor immunity in mice. Clin Cancer Res 15:4612–4621

    CAS  PubMed  Google Scholar 

  • Williamson ED, Eley SM, Griffin KF, Green M, Russell P, Leary SE, Oyston PC, Easterbrook T, Reddin KM, Robinson A et al (1995) A new improved sub-unit vaccine for plague: the basis of protection. FEMS Immunol Med Microbiol 12:223–230

    CAS  PubMed  Google Scholar 

  • Witmer-Pack MD, Swiggard WJ, Mirza A, Inaba K, Steinman RM (1995) Tissue distribution of the DEC-205 protein that is detected by the monoclonal antibody NLDC-145. II. Expression in situ in lymphoid and nonlymphoid tissues. Cell Immunol 163:157–162

    CAS  PubMed  Google Scholar 

  • Zizzari IG, Veglia F, Taurino F, Rahimi H, Quaglino E, Belleudi F, Riccardo F, Antonilli M, Napoletano C, Bellati F, Benedetti-Panici P, Torrisi MR, Frati L, Nuti M, Rughetti A (2011) HER2-based recombinant immunogen to target DCs through FcgammaRs for cancer immunotherapy. J Mol Med (Berl) 89:1231–1240

    CAS  Google Scholar 

  • Zuniga R, Lucchetti A, Galvan P, Sanchez S, Sanchez C, Hernandez A, Sanchez H, Frahm N, Linde CH, Hewitt HS, Hildebrand W, Altfeld M, Allen TM, Walker BD, Korber BT, Leitner T, Sanchez J, Brander C (2006) Relative dominance of Gag p24-specific cytotoxic T lymphocytes is associated with human immunodeficiency virus control. J Virol 80:3122–3125

    CAS  PubMed Central  PubMed  Google Scholar 

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Acknowledgment

We thank the late Dr. Ralph M. Steinman and his past colleagues for their tremendous works on DC-targeting strategy, and Dr. Seongho Ryu from Soonchunhyang Institute of Medi-bio Sciences (SIMS) for a “human body image” in the Fig. 17.1, and J-A Han for assistance with review of clinical data in Table 17.2. This work was supported by funds from the National Institutes of Health (1 R21 AI082331-01, PI. Y. Do). This study was also supported by the National Research Foundation of Korea (NRF) (2013R1A1A2005545 & 2011-0020163) and UNIST research fund (No. 1.120020.01).

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Authors and Affiliations

  1. School of Life Sciences, Ulsan National Institute of Science and Technology, UNIST-gil 50, Ulsan, 689-798, Republic of Korea

    Yoonkyung Do

  2. Cernomics Solutions, P.O. Box 1477, Frederick, MD, 21702, USA

    Bradford Powell

  3. PharmAthene, Inc., Annapolis, MD, 21401, USA

    Bradford Powell

Authors
  1. Yoonkyung Do
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  2. Bradford Powell
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Corresponding authors

Correspondence to Yoonkyung Do or Bradford Powell .

Editor information

Editors and Affiliations

  1. Apex, North Carolina, USA

    Brian K. Nunnally

  2. Pfizer BioTherapeutics Pharmaceutical Sc, Pearl River, New York, USA

    Vincent E. Turula

  3. Sitrin Solutions, Lafayette Hill, Pennsylvania, USA

    Robert D. Sitrin

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© 2015 Springer-Verlag Berlin Heidelberg

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Do, Y., Powell, B. (2015). Dendritic Cell Targeting Vaccines. In: Nunnally, B., Turula, V., Sitrin, R. (eds) Vaccine Analysis: Strategies, Principles, and Control. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-45024-6_17

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