The Nontoxic Cholera B Subunit Is a Potent Adjuvant for Intradermal DC-Targeted Vaccination.

Abstract

CD4+ T cells are major players in the immune response against several diseases; including AIDS, leishmaniasis, tuberculosis, influenza and cancer. Their activation has been successfully achieved by administering antigen coupled with antibodies, against DC-specific receptors in combination with adjuvants. Unfortunately, most of the adjuvants used so far in experimental models are unsuitable for human use. Therefore, human DC-targeted vaccination awaits the description of potent, yet nontoxic adjuvants. The nontoxic cholera B subunit (CTB) can be safely used in humans and it has the potential to activate CD4+ T cell responses. However, it remains unclear whether CTB can promote DC activation and can act as an adjuvant for DC-targeted antigens. Here, we evaluated the CTB's capacity to activate DCs and CD4+ T cell responses, and to generate long-lasting protective immunity. Intradermal (i.d.) administration of CTB promoted late and prolonged activation and accumulation of skin and lymphoid-resident DCs. When CTB was co-administered with anti-DEC205-OVA, it promoted CD4+ T cell expansion, differentiation, and infiltration to peripheral nonlymphoid tissues, i.e., the skin, lungs and intestine. Indeed, CTB promoted a polyfunctional CD4+ T cell response, including the priming of Th1 and Th17 cells, as well as resident memory T (RM) cell differentiation in peripheral nonlymphoid tissues. It is worth noting that CTB together with a DC-targeted antigen promoted local and systemic protection against experimental melanoma and murine rotavirus. We conclude that CTB administered i.d. can be used as an adjuvant to DC-targeted antigens for the induction of broad CD4+ T cell responses as well as for promoting long-lasting protective immunity.

• Authors: Laura Antonio-Herrera, Oscar Badillo-Godinez, Oscar Medina-Contreras, Araceli Tepale-Segura, Alberto García-Lozano, Lourdes Gutierrez-Xicotencatl, Gloria Soldevila, Fernando R Esquivel-Guadarrama, Juliana Idoyaga, Laura C Bonifaz
• Journal: Frontiers in immunology (Front Immunol) Vol. 9 Pg. 2212 ( 2018) ISSN: 1664-3224 [Electronic] Switzerland
• PMID: 30319653 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Adjuvants, Immunologic
• Antigens, CD
• DEC-205 receptor
• Lectins, C-Type
• Minor Histocompatibility Antigens
• Receptors, Cell Surface
• Cholera Toxin

Topics

• Adjuvants, Immunologic (administration & dosage)
• Animals
• Antigens, CD (immunology)
• Cell Line, Tumor (transplantation)
• Cholera Toxin (administration & dosage)
• Dendritic Cells (immunology)
• Disease Models, Animal
• Female
• Humans
• Injections, Intradermal
• Lectins, C-Type (antagonists & inhibitors, immunology)
• Lymphocyte Activation (immunology)
• Male
• Melanoma (immunology, prevention & control)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Mice, Transgenic
• Minor Histocompatibility Antigens (immunology)
• Receptors, Cell Surface (antagonists & inhibitors, immunology)
• Rotavirus (immunology)
• Rotavirus Infections (immunology, prevention & control, virology)
• Th1 Cells (immunology)
• Th17 Cells (immunology)
• Treatment Outcome
• Vaccination (methods)