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Front. Immunol. | doi: 10.3389/fimmu.2018.00317

Targeted Delivery of Toxoplasma gondii Antigens to Dendritic Cells Promote Immunogenicity and Protective Efficiency Against Toxoplasmosis

 Zineb Lakhrif1*,  Alexis Moreau1, Bruno Héraut1, Anne Di Tommaso1, Matthieu Juste1,  Nathalie Moiré1, Isabelle Dimier-Poisson1,  Marie-Noelle Mévélec1 and  Nicolas Aubrey1
  • 1François Rabelais University, France

Toxoplasmosis is a major public health problem and the development of a human vaccine is of high priority. Efficient vaccination against Toxoplasma gondii requires both a mucosal and systemic Th1 immune response. Moreover, dendritic cells play a critical role in orchestrating the innate immune functions and driving specific adaptive immunity to T. gondii. In this study, we explore an original vaccination strategy that combines administration via mucosal and systemic routes of fusion proteins able to target the major T. gondii surface antigen SAG1 to DCs using an antibody fragment scFv directed against DEC205 endocytic receptor. Our results show that SAG1 targeting to DCs by scFv via intranasal and subcutaneous administration improved protection against chronic T. gondii infection. A marked reduction in brain parasite burden is observed when compared with the intranasal or the subcutaneous route alone. DC targeting improved both local and systemic humoral and cellular immune responses and potentiated more specifically the Th1 response profile by more efficient production of IFN-γ, IL-2, IgG2a and nasal IgA. This study provides evidence of the potential of DC targeting for the development of new vaccines against a range of Apicomplexa parasites.

Keywords: scFv fragment antibody, DEC-205, SAG1, Vaccination, Toxoplasmosis

Received: 11 Jul 2017; Accepted: 05 Feb 2018.

Edited by:

NAHID ALI, INDIAN INSTITUTE OF CHEMICAL BIOLOGY, India

Reviewed by:

Katsuyuki Yui, Nagasaki University, Japan
Shahram Salek-ardakani, Pfizer (United States), United States  

Copyright: © 2018 Lakhrif, Moreau, Héraut, Di Tommaso, Juste, Moiré, Dimier-Poisson, Mévélec and Aubrey. 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 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. Zineb Lakhrif, François Rabelais University, UFR de Pharmacie, 31 Avenue Monge, Tours, 37200, France, zineb.lakhrif@univ-tours.fr