PMID- 25068496
OWN - NLM
STAT- MEDLINE
DCOM- 20150330
LR  - 20211021
IS  - 1873-2518 (Electronic)
IS  - 0264-410X (Print)
IS  - 0264-410X (Linking)
VI  - 32
IP  - 40
DP  - 2014 Sep 8
TI  - Fc receptor-targeting of immunogen as a strategy for enhanced antigen loading, 
      vaccination, and protection using intranasally administered antigen-pulsed 
      dendritic cells.
PG  - 5212-20
LID - S0264-410X(14)00993-1 [pii]
LID - 10.1016/j.vaccine.2014.07.050 [doi]
AB  - Dendritic cells (DCs) play a critical role in the generation of adaptive immunity 
      via the efficient capture, processing, and presentation of antigen (Ag) to naive 
      T cells. Administration of Ag-pulsed DCs is also an effective strategy for 
      enhancing immunity to tumors and infectious disease organisms. Studies have also 
      demonstrated that targeting Ags to Fcgamma receptors (FcgammaR) on Ag presenting cells 
      can enhance humoral and cellular immunity in vitro and in vivo. Specifically, our 
      studies using a Francisella tularensis (Ft) infectious disease vaccine model have 
      demonstrated that targeting immunogens to FcgammaR via intranasal (i.n.) 
      administration of monoclonal antibody (mAb)-inactivated Ft (iFt) immune complexes 
      (ICs) enhances protection against Ft challenge. Ft is the causative agent of 
      tularemia, a debilitating disease of humans and other mammals and a category A 
      biothreat agent for which there is no approved vaccine. Therefore, using iFt Ag 
      as a model immunogen, we sought to determine if ex vivo targeting of iFt to FcgammaR 
      on DCs would enhance the potency of i.n. administered iFt-pulsed DCs. In this 
      study, bone marrow-derived DCs (BMDCs) were pulsed ex vivo with iFt or mAb-iFt 
      ICs. Intranasal administration of mAb-iFt-pulsed BMDCs enhanced humoral and 
      cellular immune responses, as well as protection against Ft live vaccine strain 
      (LVS) challenge. Increased protection correlated with increased iFt loading on 
      the BMDC surface as a consequence of FcgammaR-targeting. However, the inhibitory 
      FcgammaRIIB had no impact on this enhancement. In conclusion, targeting Ag ex vivo to 
      FcgammaR on DCs provides a method for enhanced Ag loading of DCs ex vivo, thereby 
      reducing the amount of Ag required, while also avoiding the inhibitory impact of 
      FcgammaRIIB. Thus, this represents a simple and less invasive strategy for increasing 
      the potency of ex vivo-pulsed DC vaccines against chronic infectious diseases and 
      cancer.
CI  - Copyright (c) 2014 Elsevier Ltd. All rights reserved.
FAU - Pham, Giang H
AU  - Pham GH
AD  - Center for Immunology and Microbial Disease, 47 New Scotland Avenue, MC-151, 
      Albany Medical College, Albany, NY 12208, United States.
FAU - Iglesias, Bibiana V
AU  - Iglesias BV
AD  - Regeneron Pharmaceuticals, 777 Old Saw Mill River Road, Tarrytown, NY 10591, 
      United States.
FAU - Gosselin, Edmund J
AU  - Gosselin EJ
AD  - Center for Immunology and Microbial Disease, 47 New Scotland Avenue, MC-151, 
      Albany Medical College, Albany, NY 12208, United States. Electronic address: 
      gossele@mail.amc.edu.
LA  - eng
GR  - P01 AI056320/AI/NIAID NIH HHS/United States
GR  - 1R01AI100138/AI/NIAID NIH HHS/United States
GR  - R01 AI076408/AI/NIAID NIH HHS/United States
GR  - R01 AI100138/AI/NIAID NIH HHS/United States
GR  - 2P01 AI056320/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20140726
PL  - Netherlands
TA  - Vaccine
JT  - Vaccine
JID - 8406899
RN  - 0 (Antigens, Bacterial)
RN  - 0 (Bacterial Vaccines)
RN  - 0 (Cytokines)
RN  - 0 (Fc gamma receptor IIB)
RN  - 0 (Receptors, IgG)
SB  - IM
MH  - Administration, Intranasal
MH  - Animals
MH  - *Antigen Presentation
MH  - Antigens, Bacterial/immunology
MH  - Bacterial Vaccines/immunology
MH  - Cytokines/metabolism
MH  - Dendritic Cells/*immunology
MH  - Francisella tularensis
MH  - Immunity, Cellular
MH  - Immunity, Humoral
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Receptors, IgG/*immunology
MH  - Tularemia/prevention & control
MH  - Vaccination/*methods
PMC - PMC4144271
MID - NIHMS616562
OTO - NOTNLM
OT  - Cancer
OT  - Chronic infection
OT  - Dendritic cell vaccine
OT  - Fcgamma receptor-targeted vaccine
OT  - Intranasal vaccine
OT  - Vaccine platform
COIS- None of the other authors have conflicts of interest to disclose.
EDAT- 2014/07/30 06:00
MHDA- 2015/03/31 06:00
PMCR- 2015/09/08
CRDT- 2014/07/29 06:00
PHST- 2013/12/24 00:00 [received]
PHST- 2014/05/14 00:00 [revised]
PHST- 2014/07/15 00:00 [accepted]
PHST- 2014/07/29 06:00 [entrez]
PHST- 2014/07/30 06:00 [pubmed]
PHST- 2015/03/31 06:00 [medline]
PHST- 2015/09/08 00:00 [pmc-release]
AID - S0264-410X(14)00993-1 [pii]
AID - 10.1016/j.vaccine.2014.07.050 [doi]
PST - ppublish
SO  - Vaccine. 2014 Sep 8;32(40):5212-20. doi: 10.1016/j.vaccine.2014.07.050. Epub 2014 
      Jul 26.