Design of a Potent CD1d-binding NKT Cell Ligand As a Vaccine Adjuvant

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2010 Jul 10

PMID 20616071

Citations 94

Authors

Xiangming Li

Masakazu Fujio

Masakazu Imamura

Douglass Wu

Sandhya Vasan

Chi-Huey Wong

David D Ho

Moriya Tsuji

Affiliations

Soon will be listed here.

Abstract

The glycolipid alpha-galactosylceramide (alpha-GalCer) has been shown to bind CD1d molecules to activate invariant natural killer T (iNKT) cells, and subsequently induce activation of various immune-competent cells, including dendritic cells, thereby providing a significant adjuvant effect for various vaccines. However, in phase I clinical trials, alpha-GalCer was shown to display only marginal biological activity. In our search for a glycolipid that can exert more potent stimulatory activity against iNKT cells and dendritic cells and produce an adjuvant effect superior to alpha-GalCer, we performed step-wise screening assays on a focused library of 25 alpha-GalCer analogues. Assays included quantification of the magnitude of stimulatory activity against human iNKT cells in vitro, binding affinity to human and murine CD1d molecules, and binding affinity to the invariant t cell receptor of human iNKT cells. Through this rigorous and iterative screening process, we have identified a lead candidate glycolipid, 7DW8-5, that exhibits a superior adjuvant effect than alpha-GalCer on HIV and malaria vaccines in mice.

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