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An epitope-based malaria vaccine targeting the junctional region of circumsporozoite protein
A malaria vaccine that elicits long-lasting protection and is suitable for use in endemic areas remains urgently needed. Here, we assessed the immunogenicity and prophylactic efficacy of a vaccine targeting a recently described epitope on the major surface antigen on Plasmodium falciparum sporozoite...
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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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820318/ https://www.ncbi.nlm.nih.gov/pubmed/33479242 http://dx.doi.org/10.1038/s41541-020-00274-4 |
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author | Jelínková, Lucie Jhun, Hugo Eaton, Allison Petrovsky, Nikolai Zavala, Fidel Chackerian, Bryce |
author_facet | Jelínková, Lucie Jhun, Hugo Eaton, Allison Petrovsky, Nikolai Zavala, Fidel Chackerian, Bryce |
author_sort | Jelínková, Lucie |
collection | PubMed |
description | A malaria vaccine that elicits long-lasting protection and is suitable for use in endemic areas remains urgently needed. Here, we assessed the immunogenicity and prophylactic efficacy of a vaccine targeting a recently described epitope on the major surface antigen on Plasmodium falciparum sporozoites, circumsporozoite protein (CSP). Using a virus-like particle (VLP)-based vaccine platform technology, we developed a vaccine that targets the junctional region between the N-terminal and central repeat regions of CSP. This region is recognized by monoclonal antibodies, including mAb CIS43, that have been shown to potently prevent liver invasion in animal models. We show that CIS43 VLPs elicit high-titer and long-lived anti-CSP antibody responses in mice and is immunogenic in non-human primates. In mice, vaccine immunogenicity was enhanced by using mixed adjuvant formulations. Immunization with CIS43 VLPs conferred partial protection from malaria infection in a mouse model, and passive transfer of serum from immunized macaques also inhibited parasite liver invasion in the mouse infection model. Our findings demonstrate that a Qβ VLP-based vaccine targeting the CIS43 epitope combined with various adjuvants is highly immunogenic in mice and macaques, elicits long-lasting anti-CSP antibodies, and inhibits parasite infection in a mouse model. Thus, the CIS43 VLP vaccine is a promising pre-erythrocytic malaria vaccine candidate. |
format | Online Article Text |
id | pubmed-7820318 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-78203182021-01-29 An epitope-based malaria vaccine targeting the junctional region of circumsporozoite protein Jelínková, Lucie Jhun, Hugo Eaton, Allison Petrovsky, Nikolai Zavala, Fidel Chackerian, Bryce NPJ Vaccines Article A malaria vaccine that elicits long-lasting protection and is suitable for use in endemic areas remains urgently needed. Here, we assessed the immunogenicity and prophylactic efficacy of a vaccine targeting a recently described epitope on the major surface antigen on Plasmodium falciparum sporozoites, circumsporozoite protein (CSP). Using a virus-like particle (VLP)-based vaccine platform technology, we developed a vaccine that targets the junctional region between the N-terminal and central repeat regions of CSP. This region is recognized by monoclonal antibodies, including mAb CIS43, that have been shown to potently prevent liver invasion in animal models. We show that CIS43 VLPs elicit high-titer and long-lived anti-CSP antibody responses in mice and is immunogenic in non-human primates. In mice, vaccine immunogenicity was enhanced by using mixed adjuvant formulations. Immunization with CIS43 VLPs conferred partial protection from malaria infection in a mouse model, and passive transfer of serum from immunized macaques also inhibited parasite liver invasion in the mouse infection model. Our findings demonstrate that a Qβ VLP-based vaccine targeting the CIS43 epitope combined with various adjuvants is highly immunogenic in mice and macaques, elicits long-lasting anti-CSP antibodies, and inhibits parasite infection in a mouse model. Thus, the CIS43 VLP vaccine is a promising pre-erythrocytic malaria vaccine candidate. Nature Publishing Group UK 2021-01-21 /pmc/articles/PMC7820318/ /pubmed/33479242 http://dx.doi.org/10.1038/s41541-020-00274-4 Text en © The Author(s) 2021 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 Jelínková, Lucie Jhun, Hugo Eaton, Allison Petrovsky, Nikolai Zavala, Fidel Chackerian, Bryce An epitope-based malaria vaccine targeting the junctional region of circumsporozoite protein |
title | An epitope-based malaria vaccine targeting the junctional region of circumsporozoite protein |
title_full | An epitope-based malaria vaccine targeting the junctional region of circumsporozoite protein |
title_fullStr | An epitope-based malaria vaccine targeting the junctional region of circumsporozoite protein |
title_full_unstemmed | An epitope-based malaria vaccine targeting the junctional region of circumsporozoite protein |
title_short | An epitope-based malaria vaccine targeting the junctional region of circumsporozoite protein |
title_sort | epitope-based malaria vaccine targeting the junctional region of circumsporozoite protein |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820318/ https://www.ncbi.nlm.nih.gov/pubmed/33479242 http://dx.doi.org/10.1038/s41541-020-00274-4 |
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