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Sci Rep. 2017 Oct 27;7(1):14273. doi: 10.1038/s41598-017-14690-5.

Glycolipid-peptide conjugate vaccines enhance CD8+ T cell responses against human viral proteins.

Author information

1
Cancer Immunotherapy Programme, Malaghan Institute of Medical Research, Wellington, 6242, New Zealand.
2
Centre for Public Health Research, Massey University, Wellington, 6021, New Zealand.
3
The Ferrier Research Institute, Victoria University of Wellington, Lower Hutt, 5046, New Zealand.
4
Hopkirk Research Institute, Palmerston North, 4442, New Zealand.
5
Vaccine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
6
The Ferrier Research Institute, Victoria University of Wellington, Lower Hutt, 5046, New Zealand. rweinkove@malaghan.org.nz.
7
School of Biological Sciences, Victoria University of Wellington, Wellington, 6140, New Zealand.
8
Maurice Wilkins Centre, The University of Auckland, Auckland, 1142, New Zealand.
9
Cancer Immunotherapy Programme, Malaghan Institute of Medical Research, Wellington, 6242, New Zealand. Gavin.Painter@vuw.ac.nz.
10
Maurice Wilkins Centre, The University of Auckland, Auckland, 1142, New Zealand. Gavin.Painter@vuw.ac.nz.
11
Wellington Blood & Cancer Centre, Capital & Coast District Health Board, Wellington, 6021, New Zealand. Gavin.Painter@vuw.ac.nz.
12
Department of Pathology and Molecular Medicine, University of Otago Wellington, Wellington, 6021, New Zealand. Gavin.Painter@vuw.ac.nz.

Abstract

An important goal of vaccination against viruses and virus-driven cancers is to elicit cytotoxic CD8+ T cells specific for virus-derived peptides. CD8+ T cell responses can be enhanced by engaging help from natural killer T (NKT) cells. We have produced synthetic vaccines that induce strong peptide-specific CD8+ T cell responses in vivo by incorporating an NKT cell-activating glycolipid. Here we examine the effect of a glycolipid-peptide conjugate vaccine incorporating an NKT cell-activating glycolipid linked to an MHC class I-restricted peptide from a viral antigen in human peripheral blood mononuclear cells. The vaccine induces CD1d-dependent activation of human NKT cells following enzymatic cleavage, activates human dendritic cells in an NKT-cell dependent manner, and generates a pool of activated antigen-specific CD8+ T cells with cytotoxic potential. Compared to unconjugated peptide, the vaccine upregulates expression of genes encoding interferon-γ, CD137 and granzyme B. A similar vaccine incorporating a peptide from the clinically-relevant human papilloma virus (HPV) 16 E7 oncoprotein induces cytotoxicity against peptide-expressing targets in vivo, and elicits a better antitumor response in a model of E7-expressing lung cancer than its unconjugated components. Glycolipid-peptide conjugate vaccines may prove useful for the prevention or treatment of viral infections and tumors that express viral antigens.

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