Antibody Targets and Properties for Complement-Fixation Against the Circumsporozoite Protein in Malaria Immunity

The Plasmodium falciparum circumsporozoite protein (CSP) forms the basis of leading subunit malaria vaccine candidates. However, the mechanisms and specific targets of immunity are poorly defined. Recent findings suggest that antibody-mediated complement-fixation and activation play an important rol...

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Autores principales:	Liriye Kurtovic, Damien R. Drew, Arlene E. Dent, James W. Kazura, James G. Beeson
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	antibody circumsporozoite protein (CSP) complement Plasmodium falcifarum vaccines malaria Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/31fa13ebca3949d3a3c3ef8d44dbbb74
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spelling	oai:doaj.org-article:31fa13ebca3949d3a3c3ef8d44dbbb742021-12-01T23:50:48ZAntibody Targets and Properties for Complement-Fixation Against the Circumsporozoite Protein in Malaria Immunity1664-322410.3389/fimmu.2021.775659https://doaj.org/article/31fa13ebca3949d3a3c3ef8d44dbbb742021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.775659/fullhttps://doaj.org/toc/1664-3224The Plasmodium falciparum circumsporozoite protein (CSP) forms the basis of leading subunit malaria vaccine candidates. However, the mechanisms and specific targets of immunity are poorly defined. Recent findings suggest that antibody-mediated complement-fixation and activation play an important role in immunity. Here, we investigated the regions of CSP targeted by functional complement-fixing antibodies and the antibody properties associated with this activity. We quantified IgG, IgM, and functional complement-fixing antibody responses to different regions of CSP among Kenyan adults naturally exposed to malaria (n=102) and using a series of rabbit vaccination studies. Individuals who acquired functional complement-fixing antibodies had higher IgG, IgM and IgG1 and IgG3 to CSP. Acquired complement-fixing antibodies targeted the N-terminal, central-repeat, and C-terminal regions of CSP, and positive responders had greater antibody breadth compared to those who were negative for complement-fixing antibodies (p<0.05). Using rabbit vaccinations as a model, we confirmed that IgG specific to the central-repeat and non-repeat regions of CSP could effectively fix complement. However, vaccination with near full length CSP in rabbits poorly induced antibodies to the N-terminal region compared to naturally-acquired immunity in humans. Poor induction of N-terminal antibodies was also observed in a vaccination study performed in mice. IgG and IgM to all three regions of CSP play a role in mediating complement-fixation, which has important implications for malaria vaccine development.Liriye KurtovicLiriye KurtovicDamien R. DrewArlene E. DentJames W. KazuraJames G. BeesonJames G. BeesonJames G. BeesonJames G. BeesonFrontiers Media S.A.articleantibodycircumsporozoite protein (CSP)complementPlasmodium falcifarumvaccinesmalariaImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	antibody circumsporozoite protein (CSP) complement Plasmodium falcifarum vaccines malaria Immunologic diseases. Allergy RC581-607
spellingShingle	antibody circumsporozoite protein (CSP) complement Plasmodium falcifarum vaccines malaria Immunologic diseases. Allergy RC581-607 Liriye Kurtovic Liriye Kurtovic Damien R. Drew Arlene E. Dent James W. Kazura James G. Beeson James G. Beeson James G. Beeson James G. Beeson Antibody Targets and Properties for Complement-Fixation Against the Circumsporozoite Protein in Malaria Immunity
description	The Plasmodium falciparum circumsporozoite protein (CSP) forms the basis of leading subunit malaria vaccine candidates. However, the mechanisms and specific targets of immunity are poorly defined. Recent findings suggest that antibody-mediated complement-fixation and activation play an important role in immunity. Here, we investigated the regions of CSP targeted by functional complement-fixing antibodies and the antibody properties associated with this activity. We quantified IgG, IgM, and functional complement-fixing antibody responses to different regions of CSP among Kenyan adults naturally exposed to malaria (n=102) and using a series of rabbit vaccination studies. Individuals who acquired functional complement-fixing antibodies had higher IgG, IgM and IgG1 and IgG3 to CSP. Acquired complement-fixing antibodies targeted the N-terminal, central-repeat, and C-terminal regions of CSP, and positive responders had greater antibody breadth compared to those who were negative for complement-fixing antibodies (p<0.05). Using rabbit vaccinations as a model, we confirmed that IgG specific to the central-repeat and non-repeat regions of CSP could effectively fix complement. However, vaccination with near full length CSP in rabbits poorly induced antibodies to the N-terminal region compared to naturally-acquired immunity in humans. Poor induction of N-terminal antibodies was also observed in a vaccination study performed in mice. IgG and IgM to all three regions of CSP play a role in mediating complement-fixation, which has important implications for malaria vaccine development.
format	article
author	Liriye Kurtovic Liriye Kurtovic Damien R. Drew Arlene E. Dent James W. Kazura James G. Beeson James G. Beeson James G. Beeson James G. Beeson
author_facet	Liriye Kurtovic Liriye Kurtovic Damien R. Drew Arlene E. Dent James W. Kazura James G. Beeson James G. Beeson James G. Beeson James G. Beeson
author_sort	Liriye Kurtovic
title	Antibody Targets and Properties for Complement-Fixation Against the Circumsporozoite Protein in Malaria Immunity
title_short	Antibody Targets and Properties for Complement-Fixation Against the Circumsporozoite Protein in Malaria Immunity
title_full	Antibody Targets and Properties for Complement-Fixation Against the Circumsporozoite Protein in Malaria Immunity
title_fullStr	Antibody Targets and Properties for Complement-Fixation Against the Circumsporozoite Protein in Malaria Immunity
title_full_unstemmed	Antibody Targets and Properties for Complement-Fixation Against the Circumsporozoite Protein in Malaria Immunity
title_sort	antibody targets and properties for complement-fixation against the circumsporozoite protein in malaria immunity
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/31fa13ebca3949d3a3c3ef8d44dbbb74
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Antibody Targets and Properties for Complement-Fixation Against the Circumsporozoite Protein in Malaria Immunity

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