Identification of a neutralizing epitope within minor repeat region of Plasmodium falciparum CS protein

Abstract Malaria remains a major cause of morbidity and mortality worldwide with 219 million infections and 435,000 deaths predominantly in Africa. The infective Plasmodium sporozoite is the target of a potent humoral immune response that can protect murine, simian and human hosts against challenge...

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Autores principales:	J. Mauricio Calvo-Calle, Robert Mitchell, Rita Altszuler, Caroline Othoro, Elizabeth Nardin
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/34f72ef32da648fbaa7d46dfcef6289b
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spelling	oai:doaj.org-article:34f72ef32da648fbaa7d46dfcef6289b2021-12-02T15:23:47ZIdentification of a neutralizing epitope within minor repeat region of Plasmodium falciparum CS protein10.1038/s41541-020-00272-62059-0105https://doaj.org/article/34f72ef32da648fbaa7d46dfcef6289b2021-01-01T00:00:00Zhttps://doi.org/10.1038/s41541-020-00272-6https://doaj.org/toc/2059-0105Abstract Malaria remains a major cause of morbidity and mortality worldwide with 219 million infections and 435,000 deaths predominantly in Africa. The infective Plasmodium sporozoite is the target of a potent humoral immune response that can protect murine, simian and human hosts against challenge by malaria-infected mosquitoes. Early murine studies demonstrated that sporozoites or subunit vaccines based on the sporozoite major surface antigen, the circumsporozoite (CS) protein, elicit antibodies that primarily target the central repeat region of the CS protein. In the current murine studies, using monoclonal antibodies and polyclonal sera obtained following immunization with P. falciparum sporozoites or synthetic repeat peptides, we demonstrate differences in the ability of these antibodies to recognize the major and minor repeats contained in the central repeat region. The biological relevance of these differences in fine specificity was explored using a transgenic P. berghei rodent parasite expressing the P. falciparum CS repeat region. In these in vitro and in vivo studies, we demonstrate that the minor repeat region, comprised of three copies of alternating NANP and NVDP tetramer repeats, contains an epitope recognized by sporozoite-neutralizing antibodies. In contrast, murine monoclonal antibodies specific for the major CS repeats (NANP)n could be isolated from peptide-immunized mice that had limited or no sporozoite-neutralizing activity. These studies highlight the importance of assessing the fine specificity and functions of antirepeat antibodies elicited by P. falciparum CS-based vaccines and suggest that the design of immunogens to increase antibody responses to minor CS repeats may enhance vaccine efficacy.J. Mauricio Calvo-CalleRobert MitchellRita AltszulerCaroline OthoroElizabeth NardinNature PortfolioarticleImmunologic diseases. AllergyRC581-607Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Vaccines, Vol 6, Iss 1, Pp 1-8 (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 J. Mauricio Calvo-Calle Robert Mitchell Rita Altszuler Caroline Othoro Elizabeth Nardin Identification of a neutralizing epitope within minor repeat region of Plasmodium falciparum CS protein
description	Abstract Malaria remains a major cause of morbidity and mortality worldwide with 219 million infections and 435,000 deaths predominantly in Africa. The infective Plasmodium sporozoite is the target of a potent humoral immune response that can protect murine, simian and human hosts against challenge by malaria-infected mosquitoes. Early murine studies demonstrated that sporozoites or subunit vaccines based on the sporozoite major surface antigen, the circumsporozoite (CS) protein, elicit antibodies that primarily target the central repeat region of the CS protein. In the current murine studies, using monoclonal antibodies and polyclonal sera obtained following immunization with P. falciparum sporozoites or synthetic repeat peptides, we demonstrate differences in the ability of these antibodies to recognize the major and minor repeats contained in the central repeat region. The biological relevance of these differences in fine specificity was explored using a transgenic P. berghei rodent parasite expressing the P. falciparum CS repeat region. In these in vitro and in vivo studies, we demonstrate that the minor repeat region, comprised of three copies of alternating NANP and NVDP tetramer repeats, contains an epitope recognized by sporozoite-neutralizing antibodies. In contrast, murine monoclonal antibodies specific for the major CS repeats (NANP)n could be isolated from peptide-immunized mice that had limited or no sporozoite-neutralizing activity. These studies highlight the importance of assessing the fine specificity and functions of antirepeat antibodies elicited by P. falciparum CS-based vaccines and suggest that the design of immunogens to increase antibody responses to minor CS repeats may enhance vaccine efficacy.
format	article
author	J. Mauricio Calvo-Calle Robert Mitchell Rita Altszuler Caroline Othoro Elizabeth Nardin
author_facet	J. Mauricio Calvo-Calle Robert Mitchell Rita Altszuler Caroline Othoro Elizabeth Nardin
author_sort	J. Mauricio Calvo-Calle
title	Identification of a neutralizing epitope within minor repeat region of Plasmodium falciparum CS protein
title_short	Identification of a neutralizing epitope within minor repeat region of Plasmodium falciparum CS protein
title_full	Identification of a neutralizing epitope within minor repeat region of Plasmodium falciparum CS protein
title_fullStr	Identification of a neutralizing epitope within minor repeat region of Plasmodium falciparum CS protein
title_full_unstemmed	Identification of a neutralizing epitope within minor repeat region of Plasmodium falciparum CS protein
title_sort	identification of a neutralizing epitope within minor repeat region of plasmodium falciparum cs protein
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/34f72ef32da648fbaa7d46dfcef6289b
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Identification of a neutralizing epitope within minor repeat region of Plasmodium falciparum CS protein

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