Type II NKT Cell Agonist, Sulfatide, Is an Effective Adjuvant for Oral Heat-Killed Cholera Vaccines.

Aqel Albutti,Ed C Lavelle,Stephanie Longet,Alex Liddicoat,Nils Lycke,Craig P Mcentee,Lydia Lynch,Susanna Cardell,Cristiana Rîmniceanu,Shauna Quinn

doi:10.3390/vaccines9060619

Aqel Albutti, Ed C Lavelle + Show 8 more

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https://doi.org/10.3390/vaccines9060619

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Abstract

Oral vaccination has the potential to offer a safer and more efficacious approach for protection against enteric pathogens than injection-based approaches, especially in developing countries. One key advantage is the potential to induce intestinal immune responses in addition to systemic immunity. In general, antigen delivery via the oral route triggers weak immune responses or immunological tolerance. The effectiveness of oral vaccination can be improved by co-administering adjuvants. However, a major challenge is the absence of potent and safe oral adjuvants for clinical application. Here, the Type II NKT cell activator sulfatide is shown for the first time to be an effective oral adjuvant for Vibrio cholerae vaccine antigens in a mouse model. Specifically, administration of sulfatide with the oral cholera vaccine Dukoral® resulted in enhancement of intestinal antigen-specific IgA in addition to Th1 and Th17 immune responses. In summary, sulfatide is a promising adjuvant for inclusion in an oral cholera vaccine and our data further support the potential of adjuvants targeting NKT cells in new vaccine strategies.

Highlights

We demonstrated that oral administration of the Type I natural killer T (NKT) cell activator α-galactosylceramide (α-GalCer) enhanced intestinal and systemic antigen-specific humoral and cellular responses induced by experimental enterotoxigenic Escherichia coli [4], Helicobacter pylori [5] and Vibrio cholerae (V. cholerae) [6] antigens in mouse models
We previously demonstrated that the iNKT cell activator α-GalCer was an effective adjuvant to enhance intestinal antigen-specific immunoglobulin A (IgA) responses following oral coadministration of α-GalCer with Dukoral® [6], a group of mice immunised with
Consists of inactivated of Vibrio cholerae (V. cholerae) O1 Inaba and Ogawa as well as a recombinant cholera toxin B (CTB) subunit, both CTB- and bacterium-specific IgA responses were measured by Enzyme-Linked Immunosorbent Assay (ELISA) in faecal pellets and intestinal tissues were collected two weeks following the third round of immunisation

Summary

Introduction

Oral vaccines are regarded as the optimal means to fight infections caused by intestinal pathogens as the oral route can facilitate the induction of both local and systemic immune responses [1]. Adjuvants targeting natural killer T (NKT) cells have been considered in the context of oral vaccine development as these cells are enriched at intestinal sites and have the potential to bridge innate and adaptive immunity [3]. We demonstrated that oral administration of the Type I NKT cell activator α-galactosylceramide (α-GalCer) enhanced intestinal and systemic antigen-specific humoral and cellular responses induced by experimental enterotoxigenic Escherichia coli [4], Helicobacter pylori [5] and Vibrio cholerae (V. cholerae) [6] antigens in mouse models. Type II NKT cells are more abundant in humans and could be an attractive adjuvant target. A sulfated glycosphingolipid (3-O-sulfogalactosylceramide) named ‘sulfatide’ was initially found in human brains in

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