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Nanoassembly routes stimulate conflicting antibody quantity and quality for transmission-blocking malaria vaccines

Vaccine development efforts have recently focused on enabling strong immune responses to poorly immunogenic antigens, via display on multimerisation scaffolds or virus like particles (VLPs). Typically such studies demonstrate improved antibody titer comparing monomeric and nano-arrayed antigen. Ther...

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Autores principales: Leneghan, Darren B., Miura, Kazutoyo, Taylor, Iona J., Li, Yuanyuan, Jin, Jing, Brune, Karl D., Bachmann, Martin F., Howarth, Mark, Long, Carole A., Biswas, Sumi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5476561/
https://www.ncbi.nlm.nih.gov/pubmed/28630474
http://dx.doi.org/10.1038/s41598-017-03798-3
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author Leneghan, Darren B.
Miura, Kazutoyo
Taylor, Iona J.
Li, Yuanyuan
Jin, Jing
Brune, Karl D.
Bachmann, Martin F.
Howarth, Mark
Long, Carole A.
Biswas, Sumi
author_facet Leneghan, Darren B.
Miura, Kazutoyo
Taylor, Iona J.
Li, Yuanyuan
Jin, Jing
Brune, Karl D.
Bachmann, Martin F.
Howarth, Mark
Long, Carole A.
Biswas, Sumi
author_sort Leneghan, Darren B.
collection PubMed
description Vaccine development efforts have recently focused on enabling strong immune responses to poorly immunogenic antigens, via display on multimerisation scaffolds or virus like particles (VLPs). Typically such studies demonstrate improved antibody titer comparing monomeric and nano-arrayed antigen. There are many such studies and scaffold technologies, but minimal side-by-side evaluation of platforms for both the amount and efficacy of antibodies induced. Here we present direct comparison of three leading platforms displaying the promising malaria transmission-blocking vaccine (TBV) target Pfs25. These platforms encompass the three important routes to antigen-scaffold linkage: genetic fusion, chemical cross-linking and plug-and-display SpyTag/SpyCatcher conjugation. We demonstrate that chemically-conjugated Qβ VLPs elicited the highest quantity of antibodies, while SpyCatcher-AP205-VLPs elicited the highest quality anti-Pfs25 antibodies for transmission blocking upon mosquito feeding. These quantative and qualitative features will guide future nanoassembly optimisation, as well as the development of the new generation of malaria vaccines targeting transmission.
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spelling pubmed-54765612017-06-23 Nanoassembly routes stimulate conflicting antibody quantity and quality for transmission-blocking malaria vaccines Leneghan, Darren B. Miura, Kazutoyo Taylor, Iona J. Li, Yuanyuan Jin, Jing Brune, Karl D. Bachmann, Martin F. Howarth, Mark Long, Carole A. Biswas, Sumi Sci Rep Article Vaccine development efforts have recently focused on enabling strong immune responses to poorly immunogenic antigens, via display on multimerisation scaffolds or virus like particles (VLPs). Typically such studies demonstrate improved antibody titer comparing monomeric and nano-arrayed antigen. There are many such studies and scaffold technologies, but minimal side-by-side evaluation of platforms for both the amount and efficacy of antibodies induced. Here we present direct comparison of three leading platforms displaying the promising malaria transmission-blocking vaccine (TBV) target Pfs25. These platforms encompass the three important routes to antigen-scaffold linkage: genetic fusion, chemical cross-linking and plug-and-display SpyTag/SpyCatcher conjugation. We demonstrate that chemically-conjugated Qβ VLPs elicited the highest quantity of antibodies, while SpyCatcher-AP205-VLPs elicited the highest quality anti-Pfs25 antibodies for transmission blocking upon mosquito feeding. These quantative and qualitative features will guide future nanoassembly optimisation, as well as the development of the new generation of malaria vaccines targeting transmission. Nature Publishing Group UK 2017-06-19 /pmc/articles/PMC5476561/ /pubmed/28630474 http://dx.doi.org/10.1038/s41598-017-03798-3 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Leneghan, Darren B.
Miura, Kazutoyo
Taylor, Iona J.
Li, Yuanyuan
Jin, Jing
Brune, Karl D.
Bachmann, Martin F.
Howarth, Mark
Long, Carole A.
Biswas, Sumi
Nanoassembly routes stimulate conflicting antibody quantity and quality for transmission-blocking malaria vaccines
title Nanoassembly routes stimulate conflicting antibody quantity and quality for transmission-blocking malaria vaccines
title_full Nanoassembly routes stimulate conflicting antibody quantity and quality for transmission-blocking malaria vaccines
title_fullStr Nanoassembly routes stimulate conflicting antibody quantity and quality for transmission-blocking malaria vaccines
title_full_unstemmed Nanoassembly routes stimulate conflicting antibody quantity and quality for transmission-blocking malaria vaccines
title_short Nanoassembly routes stimulate conflicting antibody quantity and quality for transmission-blocking malaria vaccines
title_sort nanoassembly routes stimulate conflicting antibody quantity and quality for transmission-blocking malaria vaccines
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5476561/
https://www.ncbi.nlm.nih.gov/pubmed/28630474
http://dx.doi.org/10.1038/s41598-017-03798-3
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