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Front. Immunol. | doi: 10.3389/fimmu.2018.02212

THE NONTOXIC CHOLERA B SUBUNIT IS A POTENT ADJUVANT FOR INTRADERMAL DC-TARGETED VACCINATION

  • 1Instituto Mexicano del Seguro Social (IMSS), Mexico
  • 2Universidad Nacional Autónoma de México, Mexico
  • 3Instituto Nacional de Salud Pública (INSP), Mexico
  • 4Immunology and Proteomics Laboratory, Hospital Infantil de México Federico Gómez, Mexico
  • 5Universidad Autónoma del Estado de Morelos, Mexico
  • 6School of Medicine, Stanford University, United States

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.

Keywords: Anti-DEC205, CTb, adjuvant, Skin, Memory, T cells, Dendritic Cells

Received: 24 May 2018; Accepted: 06 Sep 2018.

Edited by:

Silvia B. Boscardin, Universidade de São Paulo, Brazil

Reviewed by:

Jesus Hernandez, Centro de Investigación en Alimentación y Desarrollo (CIAD), Mexico
Luis C S Ferreira, Universidade de São Paulo, Brazil
Adriana Flores-Langarica, University of Birmingham, United Kingdom  

Copyright: © 2018 Antonio-Herrera, Badillo, Medina-Contreras, Tepale-Segura, García-Lozano, Gutierrez-Xicotencatl, GLORIA, ESQUIVEL-GUADARRAMA, Idoyaga and Bonifaz. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Dr. Juliana Idoyaga, School of Medicine, Stanford University, Stanford, United States, jidoyaga@stanford.edu
Dr. Laura Bonifaz, Instituto Mexicano del Seguro Social (IMSS), Mexico City, 06720, Mexico, labonifaz@yahoo.com