The partial success of subunit vaccine candidates based on sporozoite proteins give rise to the belief that sporozoite surface antigens might constitute neutralizing vaccine candidates. This milestone together with the protective immunity of whole sporozoite infection and treatment vaccination can be further built upon in order to ultimately achieve protection against ECF infection with a multivalent subunit vaccine.
In the last 9 years, yeast has been tested as a way to help immune cells see and react to human pathogens such as hepatitis C virus, and cancer. Yeast has also helped chickens survive coccidiosis and pigs survive porcine circovirus infection. We are now persuading yeast to wear a coat decorated with T. parva trophies and train cattle immune cells to react appropriately (in this case to kill T. parva).
Antigen screening studies indicate that CD8 T cells from immune cattle recognise a large number of T. parva proteins, but whether or not CD8 T cells specific these proteins are all equally capable of mediating protection is not known. The lack of an antigen delivery system known to be capable of inducing protective CD8 T cell responses represents an obstacle to answering this important question.
The WSU monoclonal antibody (mAb) center was established in 1982 with a focus on developing mAb reagents for use in research. It became a formal service center of the Washington State University and CVM in 2012.
One of our strategies in the ECF Consortium is to target this stage of the sporozoite by improving the immune responses to the sporozoite antigen p67, which has shown to confer protection in previous experiments. We are about to test several nano-technologies for their ability to induce superior antibody responses, which can inhibit the infectivity of the sporozoite and eventually prevent disease.
Tremendous research progress has been made over the last ten years to better control the deadly African disease of cattle known as East Coast fever.
East Coast fever (ECF) is a lymphoproliferative disease caused by the protozoan parasite Theileria parva. It kills about one million cattle annually in Africa. Four groups of 5 BoLA-typed animals were immunized with the T. parva Tp1 antigen with or without leader sequence in the HAd5 viral vector and boosted with the same antigens in the MVA vector. Most animals generated CTL to the known epitope measured using tetramer staining, ELISpot and Cr-51-release assay. The CTL expressed perforin and lysed peptide pulsed PBMC. CD4 cells were shown to proliferate to the antigen. Challenge of the animals resulted in about 30% protection.
The parasite Theileria parva claims the life of approximately 1 million cattle every year. Immune animals to the parasite develop a lifelong immunity based on a cytotoxic T lymphocyte (CTL) response with a strong immunodominance restricted by the bovine leukocyte antigen (BoLA) class I molecules. In our goal of developing a next-generation vaccine against T. parva, we have undertaken to identify new CTL inducing antigens that can be included in a recombinant vaccine. A peptide library of 18-mer peptides overlapping by 12 amino acids and covering 500 genes of the whole parasite genome was synthesized; giving approximately 40,000 peptides aliquoted in pools of 50 peptides.
East Coast fever (ECF) is a lymphoproliferative disease caused by the protozoan parasite Theileria parva. It kills about one million cattle annually in Africa. The sporozoite stage of this parasite, harbored in the salivary glands of the tick Rhipicephalus appendiculatus, invades and establishes infection in the bovine lymphocytes during tick feeding. However, little is known about the parasite molecules involved in this infection process. It is therefore necessary to elucidate the protein composition of the sporozoites to identify novel targets for blocking invasion. Blocking this initial stage of invasion presents a promising vaccine strategy for the control of ECF.
It is well established that a primary component of East Coast Fever is parasite-driven proliferation of the cow’s lymphocytes. Unknown until now was the important role of the cow’s macrophages in driving an inflammatory response resulting in injury to blood vessels in the lung and respiratory failure.