Colocalization of a CD1d-binding glycolipid with a radiation-attenuated sporozoite vaccine in lymph node-resident dendritic cells for a robust adjuvant effect

Xiangming Li, Akira Kawamura, Chasity D. Andrews, Jessica L. Miller, Douglass Wu, Tiffany Tsao, Min Zhang, Deena Oren, Neal N. Padte, Steven A. Porcelli, Chi Huey Wong, Stefan H.I. Kappe, David D. Ho, Moriya Tsuji

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

A CD1d-binding glycolipid, a-Galactosylceramide (aGalCer), activates invariant NK T cells and acts as an adjuvant. We previously identified a fluorinated phenyl ring-modified aGalCer 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 aGalCer 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 aGalCer 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, aGalCer 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.

Original languageEnglish (US)
Pages (from-to)2710-2721
Number of pages12
JournalJournal of Immunology
Volume195
Issue number6
DOIs
StatePublished - Sep 15 2015

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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