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J Immunol. 2015 Sep 15;195(6):2710-21. doi: 10.4049/jimmunol.1403017. Epub 2015 Aug 7.

Colocalization of a CD1d-Binding Glycolipid with a Radiation-Attenuated Sporozoite Vaccine in Lymph Node-Resident Dendritic Cells for a Robust Adjuvant Effect.

Author information

1
Aaron Diamond AIDS Research Center, Affiliate of The Rockefeller University, New York, NY 10016;
2
Department of Chemistry, Hunter College of The City University of New York, New York, NY 10065;
3
Seattle Biomedical Research Institute, Seattle, WA 98109;
4
Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037;
5
Department of Pathology, New York University, New York, NY 10016;
6
Structural Biology Resource Center, The Rockefeller University, New York, NY 10065;
7
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461; and.
8
Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037; Academia Sinica, Taipei 115-74, Taiwan, Republic of China.
9
Aaron Diamond AIDS Research Center, Affiliate of The Rockefeller University, New York, NY 10016; mtsuji@adarc.org.

Abstract

A CD1d-binding glycolipid, α-Galactosylceramide (αGalCer), activates invariant NK T cells and acts as an adjuvant. We previously identified a fluorinated phenyl ring-modified αGalCer analog, 7DW8-5, displaying nearly 100-fold stronger CD1d binding affinity. In the current study, 7DW8-5 was found to exert a more potent adjuvant effect than αGalCer for a vaccine based on radiation-attenuated sporozoites of a rodent malaria parasite, Plasmodium yoelii, also referred to as irradiated P. yoelii sporozoites (IrPySpz). 7DW8-5 had a superb adjuvant effect only when the glycolipid and IrPySpz were conjointly administered i.m. Therefore, we evaluated the effect of distinctly different biodistribution patterns of αGalCer and 7DW8-5 on their respective adjuvant activities. Although both glycolipids induce a similar cytokine response in sera of mice injected i.v., after i.m. injection, αGalCer induces a systemic cytokine response, whereas 7DW8-5 is locally trapped by CD1d expressed by dendritic cells (DCs) in draining lymph nodes (dLNs). Moreover, the i.m. coadministration of 7DW8-5 with IrPySpz results in the recruitment of DCs to dLNs and the activation and maturation of DCs. These events cause the potent adjuvant effect of 7DW8-5, resulting in the enhancement of the CD8(+) T cell response induced by IrPySpz and, ultimately, improved protection against malaria. Our study is the first to show that the colocalization of a CD1d-binding invariant NK T cell-stimulatory glycolipid and a vaccine, like radiation-attenuated sporozoites, in dLN-resident DCs upon i.m. conjoint administration governs the potency of the adjuvant effect of the glycolipid.

PMID:
26254338
PMCID:
PMC4561196
DOI:
10.4049/jimmunol.1403017
[Indexed for MEDLINE]
Free PMC Article

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