Dendritic Cell-Targeted Vaccines

Cohn, Lillian B.; Delamarre, LÃ©lia

doi:10.3389/fimmu.2014.00255

Cited by 170 publications

(164 citation statements)

References 154 publications

(201 reference statements)

Supporting

Mentioning

160

Contrasting

Unclassified

Order By: Relevance

“…Although CD11c exhibited slow internalization, this receptor was not superior at generating MHC I and MHC II Ag presentation outcomes, relative to the faster internalized receptors DEC205 or CD40. Again, these data do not support the notion that slowly internalized receptors are more effective at MHC I cross-presentation (2,5). Indeed, we see no correlation between the speed of receptor internalization and MHC I or MHC II Ag presentation outcomes.…”

Section: Discussioncontrasting

confidence: 55%

“…In particular, it has been proposed that slower, more continuous Ag delivery may limit proteolysis and enable Ag presentation over an extended time period (2,5). This has yet to be tested with definitive measurements of receptor internalization kinetics.…”

mentioning

confidence: 99%

“…A ntibody-targeted vaccination is a new mode of vaccine delivery currently being exploited for clinical application (1)(2)(3). Ag is fused to Abs specific for a selected dendritic cell (DC) surface receptor.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Criteria for Dendritic Cell Receptor Selection for Efficient Antibody-Targeted Vaccination

Reuter¹,

Panozza²,

Macri³

et al. 2015

The Journal of Immunology

View full text Add to dashboard Cite

Ab-targeted vaccination involves targeting a receptor of choice expressed by dendritic cells (DCs) with Ag-coupled Abs. Currently, there is little consensus as to which criteria determine receptor selection to ensure superior Ag presentation and immunity. In this study, we investigated parameters of DC receptor internalization and determined how they impact Ag presentation outcomes. First, using mixed bone marrow chimeras, we established that Ag-targeted, but not nontargeted, DCs are responsible for Ag presentation in settings of Ab-targeted vaccination in vivo. Next, we analyzed parameters of DEC205 (CD205), Clec9A, CD11c, CD11b, and CD40 endocytosis and obtained quantitative measurements of internalization speed, surface turnover, and delivered Ag load. Exploiting these parameters in MHC class I (MHC I) and MHC class II (MHC II) Ag presentation assays, we showed that receptor expression level, proportion of surface turnover, or speed of receptor internalization did not impact MHC I or MHC II Ag presentation efficiency. Furthermore, the Ag load delivered to DCs did not correlate with the efficiency of MHC I or MHC II Ag presentation. In contrast, targeting Ag to CD8+ or CD8− DCs enhanced MHC I or MHC II Ag presentation, respectively. Therefore, receptor expression levels, speed of internalization, and/or the amount of Ag delivered can be excluded as major determinants that dictate Ag presentation efficiency in setting of Ab-targeted vaccination.

show abstract

Section: Discussioncontrasting

confidence: 55%

mentioning

confidence: 99%

See 1 more Smart Citation

Criteria for Dendritic Cell Receptor Selection for Efficient Antibody-Targeted Vaccination

Reuter¹,

Panozza²,

Macri³

et al. 2015

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…By contrast, aMHCII-vaccine proteins most likely target many different types of MHCII + APCs, perhaps explaining induction of a mixed IgG1/ IgG2a response as well as a Th1/Th2 profile [ (8,13,30), results in this study]. Similarly, aCD11c and Flt3 vaccine proteins should target both cDC1 and cDC2, contributing to the observed mixed IgG1/IgG2a responses (31)(32)(33)(34). FliC-targeted vaccines induced a mixed IgG1 (early)/IgG2a (late) response.…”

Section: Discussionmentioning

confidence: 97%

The Magnitude and IgG Subclass of Antibodies Elicited by Targeted DNA Vaccines Are Influenced by Specificity for APC Surface Molecules

et al. 2018

View full text Add to dashboard Cite

Upon APC-targeted DNA vaccination, transfected cells secrete fusion proteins with targeting units specific for surface molecules on APC. In this study, we have tested several different targeting units for their ability to influence the magnitude and subclass of Ab responses to hemagglutinin from influenza A virus. The experiments employed bivalent homodimeric Ig-based molecules (vaccibodies). The overall efficiency in BALB/c mice depended on the targeting units in the following order: αMHC class II > αCD11c > αCD40 > Xcl-1 = MIP-1α > FliC > GM-CSF > Flt-3L > αDEC205. GM-CSF induced mainly IgG1, whereas Xcl1, MIP-1α, αCD40, and αDEC205 induced predominantly IgG2a. A more balanced mixture of IgG1 and IgG2a was observed with αCD11c, αMHC class II, Flt-3L, and FliC. Similar results of IgG subclass–skewing were obtained in Th1-prone C57BL/6 mice with a more limited panel of vaccines. IgG1 responses in BALB/c occurred early after immunization but declined relatively rapidly over time. IgG2a responses appeared later but lasted longer (>252 d) than IgG1 responses. The most efficient targeting units elicited short- and long-term protection against PR8 influenza (H1N1) virus in BALB/c mice. The results suggest that targeting of Xcr1+ conventional type 1 dendritic cells preferentially induces IgG2a responses, whereas simultaneous targeting of several dendritic cell subtypes also induces IgG1 responses. The induction of distinct subclass profiles by different surface molecules supports the APC–B cell synapse hypothesis. The results may contribute to generation of more potent DNA vaccines that elicit high levels of Abs with desired biologic effector functions.

show abstract

“…Another cell group associated with asthma is the DCs, which are antigen presenting cells integral to the initiating immune responses. Although no specific study has been conducted targeting DCs by the pulmonary route, DCs exhibit tendencies for nanoparticle uptake and several ligands such as DEC-205 have been identified [84]. These targeting possibilities could be useful in applications such as vaccines.…”

Section: General Approaches For Targeting Pulmonary Delivery Of Macromentioning

confidence: 99%

Carriers for the targeted delivery of aerosolized macromolecules for pulmonary pathologies

Osman

Kaneko

Carini

et al. 2018

Expert Opinion on Drug Delivery

View full text Add to dashboard Cite

Introduction: Macromolecules with unique effects and potency are increasingly being considered for application in lung pathologies. Numerous delivery strategies for these macromolecules through the lung have been investigated to improve the targeting and overall efficacy.Areas covered: Targeting approaches from delivery devices, formulation strategies and specific targets are discussed.Expert opinion: Although macromolecules are a heterogeneous group of molecules, a number of strategies have been investigated at the macro, micro, and nanoscopic scale for the delivery of macromolecules to specific sites and cells of lung tissues. Targeted approaches are already in use at the macroscopic scale through inhalation devices and formulations, but targeting strategies at the micro and nanoscopic scale are still in the laboratory stage. The combination of controlling lung deposition and targeting after deposition, through a combination of targeting strategies could be the future direction for the treatment of lung pathologies through the pulmonary route.

show abstract

Dendritic Cell-Targeted Vaccines

Cited by 170 publications

References 154 publications

Criteria for Dendritic Cell Receptor Selection for Efficient Antibody-Targeted Vaccination

Criteria for Dendritic Cell Receptor Selection for Efficient Antibody-Targeted Vaccination

The Magnitude and IgG Subclass of Antibodies Elicited by Targeted DNA Vaccines Are Influenced by Specificity for APC Surface Molecules

Carriers for the targeted delivery of aerosolized macromolecules for pulmonary pathologies

Contact Info

Product

Resources

About