STxB as an Antigen Delivery Tool for Mucosal Vaccination

Immunotherapy against cancer and infectious disease holds the promise of high efficacy with minor side effects. Mucosal vaccines to protect against tumors or infections disease agents that affect the upper airways or the lung are still lacking, however. One mucosal vaccine candidate is the B-subunit of Shiga toxin, STxB. In this review, we compare STxB to other immunotherapy vectors. STxB is a non-toxic protein that binds to a glycosylated lipid, termed globotriaosylceramide (Gb3), which is preferentially expressed by dendritic cells. We review the use of STxB for the cross-presentation of tumor or viral antigens in a MHC class I-restricted manner to induce humoral immunity against these antigens in addition to polyfunctional and persistent CD4(+) and CD8(+) T lymphocytes capable of protecting against viral infection or tumor growth. Other literature will be summarized that documents a powerful induction of mucosal IgA and resident memory CD8(+) T cells against mucosal tumors specifically when STxB-antigen conjugates are administered via the nasal route. It will also be pointed out how STxB-based vaccines have been shown in preclinical cancer models to synergize with other therapeutic modalities (immune checkpoint inhibitors, anti-angiogenic therapy, radiotherapy). Finally, we will discuss how molecular aspects such as low immunogenicity, cross-species conservation of Gb3 expression, and lack of toxicity contribute to the competitive positioning of STxB among the different DC targeting approaches. STxB thereby appears as an original and innovative tool for the development of mucosal vaccines in infectious diseases and cancer.

Automated summary

Immunotherapy holds great promise for treating cancer and infectious diseases with high efficacy and minimal side effects. However, there is still a lack of mucosal vaccines to protect against tumors or infections affecting the upper airways or lungs. This review focuses on the B-subunit of Shiga toxin (STxB) as a potential mucosal vaccine candidate and compares it to other immunotherapy vectors. STxB has shown to induce humoral immunity and cellular immune responses, including CD4(+) and CD8(+) T lymphocytes, against tumor and viral antigens. Furthermore, STxB-based vaccines have demonstrated the ability to induce mucosal IgA and resident memory CD8(+) T cells when administered nasal route. The review also highlights the potential synergy between STxB-based vaccines and other therapeutic modalities in preclinical cancer models. The unique molecular characteristics of STxB, such as low immunogenicity and cross-species conservation of its target molecule, contribute to its competitive advantage among other dendritic cell targeting approaches. In conclusion, STxB appears as an original and innovative tool for the development of mucosal vaccines against infectious diseases and cancer.