Synergistic Effect of Two Nanotechnologies Enhances the Protective Capacity of the Theileria parva Sporozoite p67C Antigen in Cattle

J Immunol. 2021 Feb 15;206(4):686-699. doi: 10.4049/jimmunol.2000442. Epub 2021 Jan 8.

Abstract

East Coast fever (ECF), caused by Theileria parva, is the most important tick-borne disease of cattle in sub-Saharan Africa. Practical disadvantages associated with the currently used live-parasite vaccine could be overcome by subunit vaccines. An 80-aa polypeptide derived from the C-terminal portion of p67, a sporozoite surface Ag and target of neutralizing Abs, was the focus of the efforts on subunit vaccines against ECF and subjected to several vaccine trials with very promising results. However, the vaccination regimen was far from optimized, involving three inoculations of 450 μg of soluble p67C (s-p67C) Ag formulated in the Seppic adjuvant Montanide ISA 206 VG. Hence, an improved formulation of this polypeptide Ag is needed. In this study, we report on two nanotechnologies that enhance the bovine immune responses to p67C. Individually, HBcAg-p67C (chimeric hepatitis B core Ag virus-like particles displaying p67C) and silica vesicle (SV)-p67C (s-p67C adsorbed to SV-140-C18, octadecyl-modified SVs) adjuvanted with ISA 206 VG primed strong Ab and T cell responses to p67C in cattle, respectively. Coimmunization of cattle (Bos taurus) with HBcAg-p67C and SV-p67C resulted in stimulation of both high Ab titers and CD4 T cell response to p67C, leading to the highest subunit vaccine efficacy we have achieved to date with the p67C immunogen. These results offer the much-needed research depth on the innovative platforms for developing effective novel protein-based bovine vaccines to further the advancement.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antibodies, Protozoan / blood
  • CD4-Positive T-Lymphocytes / immunology*
  • Cattle
  • Hepatitis B virus / chemistry
  • Hepatitis B virus / genetics
  • Mice
  • Mineral Oil / administration & dosage
  • Nanoparticles / chemistry
  • Nanotechnology / methods*
  • Protozoan Proteins / genetics
  • Protozoan Vaccines / genetics
  • Protozoan Vaccines / immunology*
  • RAW 264.7 Cells
  • Silicon Dioxide / chemistry
  • Theileria parva / physiology*
  • Theileriasis / immunology*
  • Tick-Borne Diseases / immunology*
  • Ticks
  • Vaccination
  • Vaccines, Subunit
  • Viral Core Proteins / chemistry
  • Viral Core Proteins / genetics

Substances

  • Antibodies, Protozoan
  • Monatide (IMS 3015)
  • Protozoan Proteins
  • Protozoan Vaccines
  • Vaccines, Subunit
  • Viral Core Proteins
  • p67 antigen, Theileria
  • Silicon Dioxide
  • Mineral Oil