An epitope-based malaria vaccine targeting the junctional region of circumsporozoite protein

Abstract 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 s...

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Autores principales:	Lucie Jelínková, Hugo Jhun, Allison Eaton, Nikolai Petrovsky, Fidel Zavala, Bryce Chackerian
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/e544d49001a446b4988b1be4f00da6f4
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spelling	oai:doaj.org-article:e544d49001a446b4988b1be4f00da6f42021-12-02T15:23:47ZAn epitope-based malaria vaccine targeting the junctional region of circumsporozoite protein10.1038/s41541-020-00274-42059-0105https://doaj.org/article/e544d49001a446b4988b1be4f00da6f42021-01-01T00:00:00Zhttps://doi.org/10.1038/s41541-020-00274-4https://doaj.org/toc/2059-0105Abstract 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.Lucie JelínkováHugo JhunAllison EatonNikolai PetrovskyFidel ZavalaBryce ChackerianNature PortfolioarticleImmunologic diseases. AllergyRC581-607Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Vaccines, Vol 6, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Lucie Jelínková Hugo Jhun Allison Eaton Nikolai Petrovsky Fidel Zavala Bryce Chackerian An epitope-based malaria vaccine targeting the junctional region of circumsporozoite protein
description	Abstract 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	article
author	Lucie Jelínková Hugo Jhun Allison Eaton Nikolai Petrovsky Fidel Zavala Bryce Chackerian
author_facet	Lucie Jelínková Hugo Jhun Allison Eaton Nikolai Petrovsky Fidel Zavala Bryce Chackerian
author_sort	Lucie Jelínková
title	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_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_sort	epitope-based malaria vaccine targeting the junctional region of circumsporozoite protein
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/e544d49001a446b4988b1be4f00da6f4
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An epitope-based malaria vaccine targeting the junctional region of circumsporozoite protein

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