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

Aguado Martinez, Adriana; Silva Pinto Basto, Afonso; Müller, Joachim; Balmer, Vreni; Manser, Vera; Leitão, Alexandre; Hemphill, Andrew (2016). 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. Parasitology, 143(5), pp. 606-616. Cambridge University Press 10.1017/S0031182016000056

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Research Foci > Host-Pathogen Interaction
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Parasitology
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP)

UniBE Contributor:

Aguado Martinez, Adriana; Silva Pinto Basto, Afonso; Müller, Joachim; Balmer, Vreni; Manser, Vera and Hemphill, Andrew

Subjects:

600 Technology > 630 Agriculture

ISSN:

0031-1820

Publisher:

Cambridge University Press

Language:

English

Submitter:

Andrew Hemphill

Date Deposited:

08 Jul 2016 16:48

Last Modified:

16 Aug 2018 16:09

Publisher DOI:

10.1017/S0031182016000056

PubMed ID:

26932317

Uncontrolled Keywords:

Neosporosis; chimeric antigen; innate and adaptive immune response; outer membrane lipoprotein I; toll-like receptor 2

BORIS DOI:

10.7892/boris.82070

URI:

https://boris.unibe.ch/id/eprint/82070

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