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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

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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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