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Design and immunological evaluation of two-component protein nanoparticle vaccines for East Coast fever

Lacasta, Anna and Kim, Hyung Chan and Kepl, Elizabeth and Gachogo, Rachael and Chege, Naomi and Ojuok, Rose and Muriuki, Charity and Mwalimu, Stephen and Touboul, Gilad and Stiber, Ariel and Poole, Elizabeth Jane and Ndiwa, Nicholas and Fiala, Brooke and King, Neil P. and Nene, Vishvanath (2023) Design and immunological evaluation of two-component protein nanoparticle vaccines for East Coast fever. Frontiers in Immunology, 13 . Art. No. 1015840. ISSN 1664-3224. PMCID PMC9880323. doi:10.3389/fimmu.2022.1015840.

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Nanoparticle vaccines usually prime stronger immune responses than soluble antigens. Within this class of subunit vaccines, the recent development of computationally designed self-assembling two-component protein nanoparticle scaffolds provides a powerful and versatile platform for displaying multiple copies of one or more antigens. Here we report the generation of three different nanoparticle immunogens displaying 60 copies of p67C, an 80 amino acid polypeptide from a candidate vaccine antigen of Theileria parva, and their immunogenicity in cattle. p67C is a truncation of p67, the major surface protein of the sporozoite stage of T. parva, an apicomplexan parasite that causes an often-fatal bovine disease called East Coast fever (ECF) in sub-Saharan Africa. Compared to I32-19 and I32-28, we found that I53-50 nanoparticle scaffolds displaying p67C had the best biophysical characteristics. p67C-I53-50 also outperformed the other two nanoparticles in stimulating p67C-specific IgG1 and IgG2 antibodies and CD4⁺ T-cell responses, as well as sporozoite neutralizing capacity. In experimental cattle vaccine trials, p67C-I53-50 induced significant immunity to ECF, suggesting that the I53-50 scaffold is a promising candidate for developing novel nanoparticle vaccines. To our knowledge this is the first application of computationally designed nanoparticles to the development of livestock vaccines.

Item Type:Article
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URLURL TypeDescription CentralArticle
Lacasta, Anna0000-0001-8381-9844
Kim, Hyung Chan0000-0001-8347-1833
Muriuki, Charity0000-0002-6414-6661
Poole, Elizabeth Jane0000-0002-8570-794X
Fiala, Brooke0000-0003-0148-5268
Nene, Vishvanath0000-0001-7066-4169
Additional Information:© 2023 Lacasta, Kim, Kepl, Gachogo, Chege, Ojuok, Muriuki, Mwalimu, Touboul, Stiber, Poole, Ndiwa, Fiala, King and Nene. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. This work was funded by the Bill and Melinda Gates Foundation (OPP1156262); the UK Aid from the United Kingdom government (OPP1078791); the Norman Borlaug Commemorative Research Initiative, an initiative between the Feed the Future program of the United States Agency for International Development (USAID) and the United States Department of Agriculture (USDA)- Agricultural Research Service (58-5348-2-117F); the Livestock Vaccine Initiative Fund of the International Development Research Centre, Canada (108527), and the CGIAR Research Program on Livestock. AS was supported by the California Institute of Technology Summer Undergraduate Research Fellowships Program. We thank Ratika Krishnamurty for program management. We thank all the ILRI farm staff for animal housing and handling and the ILRI Tick Unit for provision of T. parva sporozoites and dissected salivary glands. We also thank Thomas Njoroge to his assistance in the analysis of parameters for ECF score.
Funding AgencyGrant Number
Bill and Melinda Gates FoundationOPP1156262
UK AidOPP1078791
US Agency for International DevelopmentUNSPECIFIED
Department of Agriculture58-5348-2-117F
International Development Research Centre108527
Caltech Summer Undergraduate Research Fellowship (SURF)UNSPECIFIED
PubMed Central ID:PMC9880323
Record Number:CaltechAUTHORS:20230213-466109600.27
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:119250
Deposited By: Research Services Depository
Deposited On:23 Mar 2023 23:57
Last Modified:23 Mar 2023 23:57

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