Abstract
The parasite Theileria parva is the causative agent of East Coast fever (ECF), one of the most serious cattle diseases in sub-Saharan Africa, and directly impacts smallholder farmers’ livelihoods. There is an efficient live-parasite vaccine, but issues with transmission of vaccine strains, need of a cold chain, and antibiotics limit its utilization. This has fostered research towards subunit vaccination. Cytotoxic T lymphocytes (CTL) are crucial in combating the infection by lysing T. parva-infected cells. Tp1 is an immunodominant CTL antigen, which induces Tp1-specific responses in 70–80% of cattle of the A18 or A18v haplotype during vaccination with the live vaccine. In this study, human adenovirus serotype 5 (HAd5) and modified vaccinia Ankara (MVA) were assessed for their ability to induce Tp1-specific immunity. Both viral vectors expressing the Tp1 antigen were inoculated in cattle by a heterologous prime-boost vaccination regimen. All 15 animals responded to Tp1 as determined by ELISpot. Of these, 14 reacted to the known Tp1 epitope, assayed by ELISpot and tetramer analyses, with CTL peaking 1-week post-MVA boost. Eleven animals developed CTL with specific cytotoxic activity towards peripheral blood mononuclear cells (PBMC) pulsed with the Tp1 epitope. Moreover, 36% of the animals with a Tp1 epitope-specific response survived a lethal challenge with T. parva 5 weeks post-MVA boost. Reduction of the parasitemia correlated with increased percentages of central memory lymphocytes in the Tp1 epitope-specific CD8+ populations. These results indicate that Tp1 is a promising antigen to include in a subunit vaccine and central memory cells are crucial for clearing the parasite.
Highlights
East Coast fever (ECF) is one of the most devastating tick-borne infectious diseases of cattle in sub-Saharan Africa
bovine fibroblast cells (BFC) of the A18 haplotype were infected with human adenovirus serotype 5 (HAd5) at multiplicity of infection (MOI) ranging from 1 to 100 and modified vaccinia Ankara (MVA) at an MOI of 1, the latter due to the high cytotoxicity associated with this viral vector
Substantial evidence indicates that cytotoxic CD8+ T lymphocytes induced by the Infection-and-Treatment Method” (ITM) vaccine are crucial for protecting the animals against the T. parva parasite
Summary
East Coast fever (ECF) is one of the most devastating tick-borne infectious diseases of cattle in sub-Saharan Africa. A vaccine to control this disease is of high value in affected countries and will certainly lead to improved human lives.[5] This lymphoproliferative disease is caused by a tick-borne protozoan parasite, Theileria parva, which infects African buffaloes and cattle, but only the latter develop disease. The ITM acts similar to a live-attenuated vaccine (LAV), and it has the advantage of providing long-lived immunity[9,10] as observed with other LAV such as the yellow fever, measles, or Rinderpest vaccines.[11,12] several drawbacks limit broad utilization of this vaccine It possesses the risk of spreading the disease to naïve populations as vaccinated animals can become carriers of the parasite.[13] This has impeded a broad deployment of this vaccine in several African countries due to differences in circulating strains. There is an urgent need for a more affordable, simpler, and safer vaccine
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