B subunit of Shiga toxin-based vaccines synergize with α- galactosylceramide to break tolerance against self antigen and elicit antiviral immunity

Olivier Adotevi, Benoit Vingert, Ludovic Freyburger, Protul Shrikant, Yu Chun Lone, Françoise Quintin-Colonna, Nacilla Haicheur, Mohamed Amessou, André Herbelin, Pierre Langlade-Demoyen, Wolf H. Fridman, François Lemonnier, Ludger Johannes, Eric Tartour

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

The nontoxic B subunit of Shiga toxin (STxB) targets in vivo Ag to dendritic cells that preferentially express the glycolipid Gb3 receptor. After administration of STxB chemically coupled to OVA (STxB-OVA) or E7, a polypeptide derived from HPV, in mice, we showed that the addition of α- galactosylceramide (α-GalCer) resulted in a dramatic improvement of the STxB Ag delivery system, as reflected by the more powerful and longer lasting CD8+ T cell response observed even at very low dose of immunogen (50 ng). This synergy was not found with other adjuvants (CpG, poly(I:C), IFN-α) also known to promote dendritic cell maturation. With respect to the possible mechanism explaining this synergy, mice immunized with α-GalCer presented in vivo the OVA257-264/Kb complex more significantly and for longer period than mice vaccinated with STxB alone or mixed with other adjuvants. To test whether this vaccine could break tolerance against self Ag, OVA transgenic mice were immunized with STxB-OVA alone or mixed with α-GalCer. Although no CTL induction was observed after immunization of OVA transgenic mice with STxB-OVA, tetramer assay clearly detected specific anti-OVA CD8+ T cells in 8 of 11 mice immunized with STxB-OVA combined with α-GalCer. In addition, vaccination with STxB-OVA and α-GalCer conferred strong protection against a challenge with vaccinia virus encoding OVA with virus titers in the ovaries reduced by 5 log compared with nonimmunized mice. STxB combined with α-GalCer therefore appears as a promising vaccine strategy to more successfully establish protective CD8+ T cell memory against intracellular pathogens and tumors.

Original languageEnglish (US)
Pages (from-to)3371-3379
Number of pages9
JournalJournal of Immunology
Volume179
Issue number5
StatePublished - Sep 1 2007
Externally publishedYes

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Shiga Toxin
Galactosylceramides
Autoantigens
Antiviral Agents
Immunity
Vaccines
T-Lymphocytes
Dendritic Cells
Transgenic Mice
Vaccinia virus
Viral Load
Ovary
Immunization
Vaccination
Peptides
Neoplasms

ASJC Scopus subject areas

  • Immunology

Cite this

Adotevi, O., Vingert, B., Freyburger, L., Shrikant, P., Lone, Y. C., Quintin-Colonna, F., ... Tartour, E. (2007). B subunit of Shiga toxin-based vaccines synergize with α- galactosylceramide to break tolerance against self antigen and elicit antiviral immunity. Journal of Immunology, 179(5), 3371-3379.

B subunit of Shiga toxin-based vaccines synergize with α- galactosylceramide to break tolerance against self antigen and elicit antiviral immunity. / Adotevi, Olivier; Vingert, Benoit; Freyburger, Ludovic; Shrikant, Protul; Lone, Yu Chun; Quintin-Colonna, Françoise; Haicheur, Nacilla; Amessou, Mohamed; Herbelin, André; Langlade-Demoyen, Pierre; Fridman, Wolf H.; Lemonnier, François; Johannes, Ludger; Tartour, Eric.

In: Journal of Immunology, Vol. 179, No. 5, 01.09.2007, p. 3371-3379.

Research output: Contribution to journalArticle

Adotevi, O, Vingert, B, Freyburger, L, Shrikant, P, Lone, YC, Quintin-Colonna, F, Haicheur, N, Amessou, M, Herbelin, A, Langlade-Demoyen, P, Fridman, WH, Lemonnier, F, Johannes, L & Tartour, E 2007, 'B subunit of Shiga toxin-based vaccines synergize with α- galactosylceramide to break tolerance against self antigen and elicit antiviral immunity', Journal of Immunology, vol. 179, no. 5, pp. 3371-3379.
Adotevi O, Vingert B, Freyburger L, Shrikant P, Lone YC, Quintin-Colonna F et al. B subunit of Shiga toxin-based vaccines synergize with α- galactosylceramide to break tolerance against self antigen and elicit antiviral immunity. Journal of Immunology. 2007 Sep 1;179(5):3371-3379.
Adotevi, Olivier ; Vingert, Benoit ; Freyburger, Ludovic ; Shrikant, Protul ; Lone, Yu Chun ; Quintin-Colonna, Françoise ; Haicheur, Nacilla ; Amessou, Mohamed ; Herbelin, André ; Langlade-Demoyen, Pierre ; Fridman, Wolf H. ; Lemonnier, François ; Johannes, Ludger ; Tartour, Eric. / B subunit of Shiga toxin-based vaccines synergize with α- galactosylceramide to break tolerance against self antigen and elicit antiviral immunity. In: Journal of Immunology. 2007 ; Vol. 179, No. 5. pp. 3371-3379.
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AU - Vingert, Benoit

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AU - Shrikant, Protul

AU - Lone, Yu Chun

AU - Quintin-Colonna, Françoise

AU - Haicheur, Nacilla

AU - Amessou, Mohamed

AU - Herbelin, André

AU - Langlade-Demoyen, Pierre

AU - Fridman, Wolf H.

AU - Lemonnier, François

AU - Johannes, Ludger

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N2 - The nontoxic B subunit of Shiga toxin (STxB) targets in vivo Ag to dendritic cells that preferentially express the glycolipid Gb3 receptor. After administration of STxB chemically coupled to OVA (STxB-OVA) or E7, a polypeptide derived from HPV, in mice, we showed that the addition of α- galactosylceramide (α-GalCer) resulted in a dramatic improvement of the STxB Ag delivery system, as reflected by the more powerful and longer lasting CD8+ T cell response observed even at very low dose of immunogen (50 ng). This synergy was not found with other adjuvants (CpG, poly(I:C), IFN-α) also known to promote dendritic cell maturation. With respect to the possible mechanism explaining this synergy, mice immunized with α-GalCer presented in vivo the OVA257-264/Kb complex more significantly and for longer period than mice vaccinated with STxB alone or mixed with other adjuvants. To test whether this vaccine could break tolerance against self Ag, OVA transgenic mice were immunized with STxB-OVA alone or mixed with α-GalCer. Although no CTL induction was observed after immunization of OVA transgenic mice with STxB-OVA, tetramer assay clearly detected specific anti-OVA CD8+ T cells in 8 of 11 mice immunized with STxB-OVA combined with α-GalCer. In addition, vaccination with STxB-OVA and α-GalCer conferred strong protection against a challenge with vaccinia virus encoding OVA with virus titers in the ovaries reduced by 5 log compared with nonimmunized mice. STxB combined with α-GalCer therefore appears as a promising vaccine strategy to more successfully establish protective CD8+ T cell memory against intracellular pathogens and tumors.

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