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

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

Sci Rep. 2017 Oct 27;7(1):14273

Authors: Speir M, Authier-Hall A, Brooks CR, Farrand KJ, Compton BJ, Anderson RJ, Heiser A, Osmond TL, Tang CW, Berzofsky JA, Terabe M, Painter GF, Hermans IF, Weinkove R

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.

PMID: 29079845 [PubMed - in process]

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