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Expert Rev Vaccines. 2017 Jan;16(1):73-80. Epub 2016 Nov 16.

A potent adjuvant effect of a CD1d-binding NKT cell ligand in human immune system mice.

Author information

1
a HIV and Malaria Vaccine Program, Aaron Diamond AIDS Research Center , Affiliate of The Rockefeller University , New York , NY , USA.
2
b Department of Medical Zoology , Mie University Graduate School of Medicine , Tsu , Mie , Japan.
3
c Department of Pathology , New York University School of Medicine , New York , NY , USA.

Abstract

OBJECTIVES:

A CD1d-binding invariant natural killer T (iNKT)-cell stimulatory glycolipid, namely 7DW8-5, is shown to enhance the efficacy of radiation-attenuated sporozoites (RAS)-based malaria vaccine in mice. In the current study, we aim to determine whether 7DW8-5 can display a potent adjuvant effect in human immune system (HIS) mice.

METHODS:

HIS-A2/hCD1d mice, which possess both functional human iNKT cells and CD8+ T cells, were generated by the transduction of NSG mice with adeno-associated virus serotype 9 expressing genes that encode human CD1d molecules and HLA-A*0201, followed by the engraftment of human hematopoietic stem cells. The magnitudes of human iNKT-cell response against 7DW8-5 and HLA-A*0201-restricted human CD8+ T-cell response against a human malaria antigen in HIS-A2/hCD1d mice were determined by using human CD1d tetramer and human HLA-A*0201 tetramer, respectively.

RESULTS:

We found that 7DW8-5 stimulates human iNKT cells in HIS-A2/hCD1d mice, as well as those derived from HIS-A2/hCD1d mice in vitro. We also found that 7DW8-5 significantly increases the level of a human malarial antigen-specific HLA-A*0201-restricted human CD8+ T-cell response in HIS-A2/hCD1d mice.

CONCLUSIONS:

Our study indicates that 7DW8-5 can display a potent adjuvant effect on RAS vaccine-induced anti-malarial immunity by augmenting malaria-specific human CD8+ T-cell response.

KEYWORDS:

CD1d; Malaria; NKT cell; adjuvant; glycolipid; humanized mice; sporozoites

PMID:
27801602
PMCID:
PMC5526659
DOI:
10.1080/14760584.2017.1256208
[Indexed for MEDLINE]
Free PMC Article

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