Synergistic effect of two nanotechnologies enhances the protective capacity of the Theileria parva sporozoite p67C antigen in cattle

Anna Lacasta, Karishma T. Mody, Ine De Goeyse, Chengzhong Yu, Jun Zhang, James Nyagwange, Stephen Mwalimu, Elias Awino, Rosemary Saya, Thomas Njoroge, Robert Muriuki, Nicholas Ndiwa, Elisabeth Jane Poole, Bing Zhang, Antonino Cavallaro, Timothy J. Mahony, Lucilla Steinaa, Neena Mitter, Vishvanath Nene

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    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-C 18, 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.

    Original languageEnglish
    JournalJournal of Immunology
    Volume206
    Issue number4
    Pages (from-to)686-699
    Number of pages14
    ISSN0022-1767
    DOIs
    Publication statusPublished - 2021

    Keywords

    • HEPATITIS-B CORE
    • EAST-COAST FEVER
    • SILICA NANOPARTICLES
    • ENTEROVIRUS 71
    • CELL EPITOPES
    • IMMUNITY
    • ANTIBODY
    • PROTEIN
    • PARTICLES
    • SEQUENCE

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