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N-terminal fusion of a toll-like receptor 2-ligand to a Neospora caninum chimeric antigen efficiently modifies the properties of the specific immune response

Published online by Cambridge University Press:  02 March 2016

ADRIANA AGUADO-MARTÍNEZ ,
AFONSO P. BASTO ,
JOACHIM MÜLLER ,
VRENI BALMER ,
VERA MANSER ,
ALEXANDRE LEITÃO  and
ANDREW HEMPHILL
ADRIANA AGUADO-MARTÍNEZ*
Affiliation:
Institute for Parasitology, Vetsuisse Faculty, University of Berne, Länggass-Strasse 122, CH-3012 Bern, Switzerland
AFONSO P. BASTO
Affiliation:
CIISA, Faculdade de Medicina Veterinária, ULisboa, Avenida da Universidade Técnica, 1300–477 Lisboa, Portugal
JOACHIM MÜLLER
Affiliation:
Institute for Parasitology, Vetsuisse Faculty, University of Berne, Länggass-Strasse 122, CH-3012 Bern, Switzerland
VRENI BALMER
Affiliation:
Institute for Parasitology, Vetsuisse Faculty, University of Berne, Länggass-Strasse 122, CH-3012 Bern, Switzerland
VERA MANSER
Affiliation:
Institute for Parasitology, Vetsuisse Faculty, University of Berne, Länggass-Strasse 122, CH-3012 Bern, Switzerland
ALEXANDRE LEITÃO
Affiliation:
CIISA, Faculdade de Medicina Veterinária, ULisboa, Avenida da Universidade Técnica, 1300–477 Lisboa, Portugal
ANDREW HEMPHILL
Affiliation:
Institute for Parasitology, Vetsuisse Faculty, University of Berne, Länggass-Strasse 122, CH-3012 Bern, Switzerland
*
*Corresponding author: Institute of Parasitology, University of Bern, Länggas-Strasse 122, 3012 Bern, Switzerland. Tel: +41 31 631 2593. Fax: +41 31 631 2477. E-mail: adriana.aguado@vetsuisse.unibe.ch
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Summary

Immunoprophylactic products against neosporosis during pregnancy should induce an appropriately balanced immune response. In this respect, OprI, a bacterial lipoprotein targeting toll like receptor (TLR)2, provides promising adjuvant properties. We report on the manipulation of the innate and the T-cell immune response through the fusion of OprI with the Neospora caninum chimeric protein Mic3-1-R. In contrast to Mic3-1-R, OprI-MIC3-1-R significantly activated bone-marrow dendritic cells from naïve mice. Mice immunized with OprI-Mic3-1-R induced an immune response with mixed T helper (Th)1 and Th2 properties (high levels of both immunoglobulin (Ig)G1 and IgG2a and of interleukin (IL)-10, IL-12(p70) and interferon-γ responses) whereas Mic3-1-R+saponin induced a clear Th2-biased response (low IgG2a and high IL-4 and IL-10). After mating and challenge with N. caninum, increased expression of interferon-γ was only found in placentas from OprI-Mic3-1-R immunized dams. However, no protection against vertical transmission and neonatal mortality was observed in either of the two groups. These results indicated that more exhaustive studies must be done to elucidate the immune mechanisms associated with transplacental transmission. Antigen linkage to TLR2-ligands, such as OprI, is a useful tool to investigate this enigma by reorienting the innate and adaptive immune responses against other candidate antigens in future studies.

Keywords

Neosporosisinnate and adaptive immune responseouter membrane lipoprotein Itoll-like receptor 2chimeric antigen
Type
Research Article
Information
Parasitology , Volume 143 , Issue 5 , April 2016 , pp. 606 - 616
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Copyright
Copyright © Cambridge University Press 2016 

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