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

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Title Design and immunological evaluation of two-component protein nanoparticle vaccines for East Coast fever
 
Creator Lacasta, Anna
Kim, H.C.
Kepl, E.
Gachogo, Rachael
Chege, Naomi
Ojuok, Rose
Muriuki, Charity
Mwalimu, Stephen
Touboul, G.
Stiber, A.
Poole, Elizabeth J.
Ndiwa, Nicholas N.
Fiala, B.
King, N.P.
Nene, Vishvanath
 
Subject vaccines
animal diseases
east coast fever
 
Description 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.
 
Date 2023-01-13
2023-01-13T13:49:50Z
2023-01-13T13:49:50Z
 
Type Journal Article
 
Identifier Lacasta, A., Kim, H.C., Kepl, E., Gachogo, R., Chege, N., Ojuok, R., Muriuki, C., Mwalimu, S., Touboul, G., Stiber, A., Poole, E.J., Ndiwa, N., Fiala, B., King, N.P. and Nene, V. 2023. Design and immunological evaluation of two-component protein nanoparticle vaccines for East Coast fever. Frontiers in Immunology 13: 1015840.
1664-3224
https://hdl.handle.net/10568/127050
https://doi.org/10.3389/fimmu.2022.1015840
 
Language en
 
Rights CC-BY-4.0
Open Access
 
Format 1015840
 
Publisher Frontiers Media SA
 
Source Frontiers in Immunology