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In vitro and in vivo inhibition of malaria parasite infection by monoclonal antibodies against Plasmodium falciparum circumsporozoite protein (CSP)
Plasmodium falciparum malaria contributes to a significant global disease burden. Circumsporozoite protein (CSP), the most abundant sporozoite stage antigen, is a prime vaccine candidate. Inhibitory monoclonal antibodies (mAbs) against CSP map to either a short junctional sequence or the central (NP...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970865/ https://www.ncbi.nlm.nih.gov/pubmed/33674699 http://dx.doi.org/10.1038/s41598-021-84622-x |
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author | Livingstone, Merricka C. Bitzer, Alexis A. Giri, Alish Luo, Kun Sankhala, Rajeshwer S. Choe, Misook Zou, Xiaoyan Dennison, S. Moses Li, Yuanzhang Washington, William Ngauy, Viseth Tomaras, Georgia D. Joyce, M. Gordon Batchelor, Adrian H. Dutta, Sheetij |
author_facet | Livingstone, Merricka C. Bitzer, Alexis A. Giri, Alish Luo, Kun Sankhala, Rajeshwer S. Choe, Misook Zou, Xiaoyan Dennison, S. Moses Li, Yuanzhang Washington, William Ngauy, Viseth Tomaras, Georgia D. Joyce, M. Gordon Batchelor, Adrian H. Dutta, Sheetij |
author_sort | Livingstone, Merricka C. |
collection | PubMed |
description | Plasmodium falciparum malaria contributes to a significant global disease burden. Circumsporozoite protein (CSP), the most abundant sporozoite stage antigen, is a prime vaccine candidate. Inhibitory monoclonal antibodies (mAbs) against CSP map to either a short junctional sequence or the central (NPNA)(n) repeat region. We compared in vitro and in vivo activities of six CSP-specific mAbs derived from human recipients of a recombinant CSP vaccine RTS,S/AS01 (mAbs 317 and 311); an irradiated whole sporozoite vaccine PfSPZ (mAbs CIS43 and MGG4); or individuals exposed to malaria (mAbs 580 and 663). RTS,S mAb 317 that specifically binds the (NPNA)(n) epitope, had the highest affinity and it elicited the best sterile protection in mice. The most potent inhibitor of sporozoite invasion in vitro was mAb CIS43 which shows dual-specific binding to the junctional sequence and (NPNA)(n). In vivo mouse protection was associated with the mAb reactivity to the NANPx6 peptide, the in vitro inhibition of sporozoite invasion activity, and kinetic parameters measured using intact mAbs or their Fab fragments. Buried surface area between mAb and its target epitope was also associated with in vivo protection. Association and disconnects between in vitro and in vivo readouts has important implications for the design and down-selection of the next generation of CSP based interventions. |
format | Online Article Text |
id | pubmed-7970865 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-79708652021-03-19 In vitro and in vivo inhibition of malaria parasite infection by monoclonal antibodies against Plasmodium falciparum circumsporozoite protein (CSP) Livingstone, Merricka C. Bitzer, Alexis A. Giri, Alish Luo, Kun Sankhala, Rajeshwer S. Choe, Misook Zou, Xiaoyan Dennison, S. Moses Li, Yuanzhang Washington, William Ngauy, Viseth Tomaras, Georgia D. Joyce, M. Gordon Batchelor, Adrian H. Dutta, Sheetij Sci Rep Article Plasmodium falciparum malaria contributes to a significant global disease burden. Circumsporozoite protein (CSP), the most abundant sporozoite stage antigen, is a prime vaccine candidate. Inhibitory monoclonal antibodies (mAbs) against CSP map to either a short junctional sequence or the central (NPNA)(n) repeat region. We compared in vitro and in vivo activities of six CSP-specific mAbs derived from human recipients of a recombinant CSP vaccine RTS,S/AS01 (mAbs 317 and 311); an irradiated whole sporozoite vaccine PfSPZ (mAbs CIS43 and MGG4); or individuals exposed to malaria (mAbs 580 and 663). RTS,S mAb 317 that specifically binds the (NPNA)(n) epitope, had the highest affinity and it elicited the best sterile protection in mice. The most potent inhibitor of sporozoite invasion in vitro was mAb CIS43 which shows dual-specific binding to the junctional sequence and (NPNA)(n). In vivo mouse protection was associated with the mAb reactivity to the NANPx6 peptide, the in vitro inhibition of sporozoite invasion activity, and kinetic parameters measured using intact mAbs or their Fab fragments. Buried surface area between mAb and its target epitope was also associated with in vivo protection. Association and disconnects between in vitro and in vivo readouts has important implications for the design and down-selection of the next generation of CSP based interventions. Nature Publishing Group UK 2021-03-05 /pmc/articles/PMC7970865/ /pubmed/33674699 http://dx.doi.org/10.1038/s41598-021-84622-x Text en © This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2021 https://creativecommons.org/licenses/by/4.0/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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Livingstone, Merricka C. Bitzer, Alexis A. Giri, Alish Luo, Kun Sankhala, Rajeshwer S. Choe, Misook Zou, Xiaoyan Dennison, S. Moses Li, Yuanzhang Washington, William Ngauy, Viseth Tomaras, Georgia D. Joyce, M. Gordon Batchelor, Adrian H. Dutta, Sheetij In vitro and in vivo inhibition of malaria parasite infection by monoclonal antibodies against Plasmodium falciparum circumsporozoite protein (CSP) |
title | In vitro and in vivo inhibition of malaria parasite infection by monoclonal antibodies against Plasmodium falciparum circumsporozoite protein (CSP) |
title_full | In vitro and in vivo inhibition of malaria parasite infection by monoclonal antibodies against Plasmodium falciparum circumsporozoite protein (CSP) |
title_fullStr | In vitro and in vivo inhibition of malaria parasite infection by monoclonal antibodies against Plasmodium falciparum circumsporozoite protein (CSP) |
title_full_unstemmed | In vitro and in vivo inhibition of malaria parasite infection by monoclonal antibodies against Plasmodium falciparum circumsporozoite protein (CSP) |
title_short | In vitro and in vivo inhibition of malaria parasite infection by monoclonal antibodies against Plasmodium falciparum circumsporozoite protein (CSP) |
title_sort | in vitro and in vivo inhibition of malaria parasite infection by monoclonal antibodies against plasmodium falciparum circumsporozoite protein (csp) |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970865/ https://www.ncbi.nlm.nih.gov/pubmed/33674699 http://dx.doi.org/10.1038/s41598-021-84622-x |
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