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

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.

[1]  S. Górska,et al.  Technological Approaches for Improving Vaccination Compliance and Coverage , 2020, Vaccines.

[2]  J. Holmgren,et al.  An oral alpha-galactosylceramide adjuvanted Helicobacter pylori vaccine induces protective IL-1R- and IL-17R-dependent Th1 responses , 2019, npj Vaccines.

[3]  M. Lebens,et al.  Alpha-galactosylceramide enhances mucosal immunity to oral whole-cell cholera vaccines , 2019, Mucosal Immunology.

[4]  Xiaoshun He,et al.  The Role of CD1d and MR1 Restricted T Cells in the Liver , 2018, Front. Immunol..

[5]  S. Cardell,et al.  Type II NKT Cells: An Elusive Population With Immunoregulatory Properties , 2018, Front. Immunol..

[6]  A. Ishizu,et al.  CD1d-Restricted Type II NKT Cells Reactive With Endogenous Hydrophobic Peptides , 2018, Front. Immunol..

[7]  N. Peppas,et al.  Current state and challenges in developing oral vaccines. , 2017, Advanced drug delivery reviews.

[8]  M. Dhodapkar,et al.  Type II NKT Cells and Their Emerging Role in Health and Disease , 2017, The Journal of Immunology.

[9]  K. Chayama,et al.  Choline Deficiency Causes Colonic Type II Natural Killer T (NKT) Cell Loss and Alleviates Murine Colitis under Type I NKT Cell Deficiency , 2017, PloS one.

[10]  J. Holmgren,et al.  A novel adjuvanted capsule based strategy for oral vaccination against infectious diarrhoeal pathogens. , 2016, Journal of controlled release : official journal of the Controlled Release Society.

[11]  S. Zeissig,et al.  Control of intestinal homeostasis through crosstalk between natural killer T cells and the intestinal microbiota. , 2015, Clinical immunology.

[12]  M. Kasahara,et al.  Establishment of a vascular endothelial cell-reactive type II NKT cell clone from a rat model of autoimmune vasculitis. , 2015, International immunology.

[13]  E. Lavelle,et al.  Harnessing the antibacterial and immunological properties of mucosal-associated invariant T cells in the development of novel oral vaccines against enteric infections. , 2014, Biochemical pharmacology.

[14]  K. Honke.  Biosynthesis and biological function of sulfoglycolipids , 2013, Proceedings of the Japan Academy. Series B, Physical and biological sciences.

[15]  J. Månsson,et al.  Sulfatide Attenuates Experimental Staphylococcus aureus Sepsis through a CD1d-Dependent Pathway , 2013, Infection and Immunity.

[16]  C. Elson,et al.  Th17 Cells Upregulate Polymeric Ig Receptor and Intestinal IgA and Contribute to Intestinal Homeostasis , 2012, The Journal of Immunology.

[17]  G. A. Lang,et al.  Type II NKT cells facilitate Alum‐sensing and humoral immunity , 2012, Journal of leukocyte biology.

[18]  E. Adams,et al.  The majority of CD1d‐sulfatide‐specific T cells in human blood use a semiinvariant Vδ1 TCR , 2012, European journal of immunology.

[19]  Michael J. Podolsky,et al.  Vibrio cholerae O1 Infection Induces Proinflammatory CD4+ T-Cell Responses in Blood and Intestinal Mucosa of Infected Humans , 2011, Clinical and Vaccine Immunology.

[20]  I. Maričić,et al.  Sulfatide-mediated activation of type II natural killer T cells prevents hepatic ischemic reperfusion injury in mice. , 2011, Gastroenterology.

[21]  P. Insel,et al.  Mucosal adjuvant activity of cholera toxin requires Th17 cells and protects against inhalation anthrax , 2010, Proceedings of the National Academy of Sciences.

[22]  I. Maričić,et al.  Sulfatide administration leads to inhibition of HIV-1 replication and enhanced hematopoeisis. , 2010, Journal of stem cells.

[23]  M. Arifuzzaman,et al.  Memory T-Cell Responses to Vibrio cholerae O1 Infection , 2009, Infection and Immunity.

[24]  J. Wrammert,et al.  Antigen-Specific Memory B-Cell Responses to Vibrio cholerae O1 Infection in Bangladesh , 2009, Infection and Immunity.

[25]  M. Hattori,et al.  Cd1d-dependent regulation of bacterial colonization in the intestine of mice. , 2009, The Journal of clinical investigation.

[26]  S. Lundin,et al.  Cholera Caused by Vibrio cholerae O1 Induces T-Cell Responses in the Circulation , 2009, Infection and Immunity.

[27]  M. Lebens,et al.  Sulfatide Recognition by Colonization Factor Antigen CS6 from Enterotoxigenic Escherichia coli , 2009, PloS one.

[28]  Firdausi Qadri,et al.  Susceptibility to Vibrio cholerae Infection in a Cohort of Household Contacts of Patients with Cholera in Bangladesh , 2008, PLoS neglected tropical diseases.

[29]  J. Berzofsky,et al.  Cross-Regulation between Type I and Type II NKT Cells in Regulating Tumor Immunity: A New Immunoregulatory Axis1 , 2007, The Journal of Immunology.

[30]  I. Maričić,et al.  Type II NKT cell-mediated anergy induction in type I NKT cells prevents inflammatory liver disease. , 2007, The Journal of clinical investigation.

[31]  I. Maričić,et al.  Prevention of Autoimmunity by Targeting a Distinct, Noninvariant CD1d-reactive T Cell Population Reactive to Sulfatide , 2004, The Journal of experimental medicine.

[32]  G. De Libero,et al.  Presentation of the Same Glycolipid by Different CD1 Molecules , 2002, The Journal of experimental medicine.

[33]  D. Schifferli,et al.  Lysine Residue 117 of the FasG Adhesin of Enterotoxigenic Escherichia coli Is Essential for Binding of 987P Fimbriae to Sulfatide , 1999, Infection and Immunity.

[34]  D. Zurakowski,et al.  A statistically defined endpoint titer determination method for immunoassays. , 1998, Journal of immunological methods.

[35]  K. Schön,et al.  Interferon‐γ receptor‐deficient mice exhibit impaired gut mucosal immune responses but intact oral tolerance , 1997, Immunology.

[36]  C. Czerkinsky,et al.  "PERFEXT": a direct method for quantitative assessment of cytokine production in vivo at the local level. , 1997, Research in immunology.

[37]  K. Sugano,et al.  Role of sulfatides in adhesion of Helicobacter pylori to gastric cancer cells , 1996, Infection and immunity.

[38]  K. Schön,et al.  Paradoxical IgA immunity in CD4-deficient mice. Lack of cholera toxin-specific protective immunity despite normal gut mucosal IgA differentiation. , 1995, Journal of immunology.