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<p>Recent advances in our understanding of immune tolerance, particularly the role of immune checkpoints in peripheral tolerance, have opened promising new avenues for therapeutic interventions in immune-related disorders. In this study, we developed a novel class of tolerogenic vaccines based on recombinant virus-like particles (tVLPs), engineered to display the immune checkpoint molecule CTLA-4 on their surface and incorporate specific antigens. These tVLPs promote the differentiation of tolerogenic dendritic cells (DCs) in vitro, characterized by a distinct functional phenotype and associated transcriptomic alterations. Furthermore, tVLPs inhibit DC activation and specifically modulate the antigen-specific T cell compartment, inducing a hyporesponsive state in effector T cells while promoting the activation of regulatory T cells (Tregs). The therapeutic efficacy of tVLPs was demonstrated in a murine model of food allergy, where five consecutive daily injections conferred protection against allergic symptoms and anaphylactic shock. Importantly, this effect was antigen-specific, long-lasting, and dependent on Tregs, as evidenced by the transfer of protection to naïve mice following adoptive transfer of Tregs from vaccinated animals. These findings establish tVLPs as a promising platform for the development of targeted immunotherapies for allergies and autoimmune diseases.</p>

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Immune checkpoint-engineered virus-like particles induce antigen-specific immune tolerance and protect against food allergy

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月29日

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  • Pierre-Axel Vinot,
  • James Vigneron,
  • Julie Marsande,
  • Béatrice Levacher,
  • Nicolas Tchitchek,
  • David Klatzmann,
  • Bertrand Bellier

摘要

Recent advances in our understanding of immune tolerance, particularly the role of immune checkpoints in peripheral tolerance, have opened promising new avenues for therapeutic interventions in immune-related disorders. In this study, we developed a novel class of tolerogenic vaccines based on recombinant virus-like particles (tVLPs), engineered to display the immune checkpoint molecule CTLA-4 on their surface and incorporate specific antigens. These tVLPs promote the differentiation of tolerogenic dendritic cells (DCs) in vitro, characterized by a distinct functional phenotype and associated transcriptomic alterations. Furthermore, tVLPs inhibit DC activation and specifically modulate the antigen-specific T cell compartment, inducing a hyporesponsive state in effector T cells while promoting the activation of regulatory T cells (Tregs). The therapeutic efficacy of tVLPs was demonstrated in a murine model of food allergy, where five consecutive daily injections conferred protection against allergic symptoms and anaphylactic shock. Importantly, this effect was antigen-specific, long-lasting, and dependent on Tregs, as evidenced by the transfer of protection to naïve mice following adoptive transfer of Tregs from vaccinated animals. These findings establish tVLPs as a promising platform for the development of targeted immunotherapies for allergies and autoimmune diseases.