Fusion of foreign T-cell epitopes and addition of TLR agonists enhance immunity against Neospora caninum profilin in cattle

Parasite Immunol. 2016 Nov;38(11):663-669. doi: 10.1111/pim.12354. Epub 2016 Oct 4.

Abstract

We demonstrated recently that immunization with recombinant Neospora caninum profilin (rNcPRO) induces limited protection and a regulatory T-cell response in mice. The aim of this study was to evaluate the immune response elicited by rNcPRO in cattle and assess a strategy to enhance its immunogenicity, combining the addition of T-cell epitopes and immune modulators. We developed a chimeric recombinant profilin fused to functional T-cell epitopes present in the N-terminal sequence of vesicular stomatitis virus (VSV) glycoprotein G (rNcPRO/G). Groups of three cattle were immunized with two doses (2 weeks apart) of rNcPRO or rNcPRO/G formulated with alum hydroxide or a nanoparticulated soya-based adjuvant enriched with Toll-like receptor (TLR) 2 and TLR9 agonists, aimed to tackle the MyD88 pathway (AVECplus). rNcPRO induced only a primary immune response (IgM mediated), while antibodies in rNcPRO/G-vaccinated animals switched to IgG1 after the booster. The vaccine formulated with rNcPRO/G and AVECplus improved the production of systemic IFN-γ and induced long-term recall B-cell responses. Overall, our study provides data supporting the use of T-cell epitopes from VSV glycoprotein G and TLR agonists to enhance and modulate immunity to peptide antigens in bovines, particularly when using small proteins from parasites for which immune responses are usually feeble.

Keywords: Neospora caninum; cattle; profilin; recombinant vaccines.

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Animals
  • Antibodies, Protozoan / immunology
  • B-Lymphocytes / immunology
  • Cattle
  • Cattle Diseases / immunology*
  • Coccidiosis / immunology
  • Coccidiosis / veterinary*
  • Epitopes, T-Lymphocyte
  • Female
  • Immunoglobulin G
  • Interferon-gamma / immunology
  • Mice
  • Neospora / physiology*
  • Profilins / analysis
  • Profilins / genetics
  • Protozoan Vaccines / administration & dosage
  • Protozoan Vaccines / immunology*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology
  • Recombinant Proteins / metabolism
  • T-Lymphocytes, Regulatory / immunology
  • Toll-Like Receptors / agonists*

Substances

  • Adjuvants, Immunologic
  • Antibodies, Protozoan
  • Epitopes, T-Lymphocyte
  • Immunoglobulin G
  • Profilins
  • Protozoan Vaccines
  • Recombinant Fusion Proteins
  • Recombinant Proteins
  • Toll-Like Receptors
  • Interferon-gamma