Subclass and avidity of circumsporozoite protein specific antibodies associate with protection status against malaria infection

Abstract RTS,S/AS01 is an advanced pre-erythrocytic malaria vaccine candidate with demonstrated vaccine efficacy up to 86.7% in controlled human malaria infection (CHMI) studies; however, reproducible immune correlates of protection (CoP) are elusive. To identify candidates of humoral correlates of...

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Autores principales:	Kelly E. Seaton, Rachel L. Spreng, Milite Abraha, Matthew Reichartz, Michelle Rojas, Frederick Feely, Richard H. C. Huntwork, Sheetij Dutta, Sarah V. Mudrak, S. Munir Alam, Scott Gregory, Erik Jongert, Margherita Coccia, Fernando Ulloa-Montoya, Ulrike Wille-Reece, Georgia D. Tomaras, S. Moses Dennison
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/0219a60f06354a4495a0f6088c161287
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spelling	oai:doaj.org-article:0219a60f06354a4495a0f6088c1612872021-12-02T19:09:19ZSubclass and avidity of circumsporozoite protein specific antibodies associate with protection status against malaria infection10.1038/s41541-021-00372-x2059-0105https://doaj.org/article/0219a60f06354a4495a0f6088c1612872021-08-01T00:00:00Zhttps://doi.org/10.1038/s41541-021-00372-xhttps://doaj.org/toc/2059-0105Abstract RTS,S/AS01 is an advanced pre-erythrocytic malaria vaccine candidate with demonstrated vaccine efficacy up to 86.7% in controlled human malaria infection (CHMI) studies; however, reproducible immune correlates of protection (CoP) are elusive. To identify candidates of humoral correlates of vaccine mediated protection, we measured antibody magnitude, subclass, and avidity for Plasmodium falciparum (Pf) circumsporozoite protein (CSP) by multiplex assays in two CHMI studies with varying RTS,S/AS01B vaccine dose and timing regimens. Central repeat (NANP6) IgG1 magnitude correlated best with protection status in univariate analyses and was the most predictive for protection in a multivariate model. NANP6 IgG3 magnitude, CSP IgG1 magnitude, and total serum antibody dissociation phase area-under-the-curve for NANP6, CSP, NPNA3, and N-interface binding were also associated with protection status in the regimen adjusted univariate analysis. Identification of multiple immune response features that associate with protection status, such as antibody subclasses, fine specificity and avidity reported here may accelerate development of highly efficacious vaccines against P. falciparum.Kelly E. SeatonRachel L. SprengMilite AbrahaMatthew ReichartzMichelle RojasFrederick FeelyRichard H. C. HuntworkSheetij DuttaSarah V. MudrakS. Munir AlamScott GregoryErik JongertMargherita CocciaFernando Ulloa-MontoyaUlrike Wille-ReeceGeorgia D. TomarasS. Moses DennisonNature PortfolioarticleImmunologic diseases. AllergyRC581-607Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Vaccines, Vol 6, Iss 1, Pp 1-13 (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 Kelly E. Seaton Rachel L. Spreng Milite Abraha Matthew Reichartz Michelle Rojas Frederick Feely Richard H. C. Huntwork Sheetij Dutta Sarah V. Mudrak S. Munir Alam Scott Gregory Erik Jongert Margherita Coccia Fernando Ulloa-Montoya Ulrike Wille-Reece Georgia D. Tomaras S. Moses Dennison Subclass and avidity of circumsporozoite protein specific antibodies associate with protection status against malaria infection
description	Abstract RTS,S/AS01 is an advanced pre-erythrocytic malaria vaccine candidate with demonstrated vaccine efficacy up to 86.7% in controlled human malaria infection (CHMI) studies; however, reproducible immune correlates of protection (CoP) are elusive. To identify candidates of humoral correlates of vaccine mediated protection, we measured antibody magnitude, subclass, and avidity for Plasmodium falciparum (Pf) circumsporozoite protein (CSP) by multiplex assays in two CHMI studies with varying RTS,S/AS01B vaccine dose and timing regimens. Central repeat (NANP6) IgG1 magnitude correlated best with protection status in univariate analyses and was the most predictive for protection in a multivariate model. NANP6 IgG3 magnitude, CSP IgG1 magnitude, and total serum antibody dissociation phase area-under-the-curve for NANP6, CSP, NPNA3, and N-interface binding were also associated with protection status in the regimen adjusted univariate analysis. Identification of multiple immune response features that associate with protection status, such as antibody subclasses, fine specificity and avidity reported here may accelerate development of highly efficacious vaccines against P. falciparum.
format	article
author	Kelly E. Seaton Rachel L. Spreng Milite Abraha Matthew Reichartz Michelle Rojas Frederick Feely Richard H. C. Huntwork Sheetij Dutta Sarah V. Mudrak S. Munir Alam Scott Gregory Erik Jongert Margherita Coccia Fernando Ulloa-Montoya Ulrike Wille-Reece Georgia D. Tomaras S. Moses Dennison
author_facet	Kelly E. Seaton Rachel L. Spreng Milite Abraha Matthew Reichartz Michelle Rojas Frederick Feely Richard H. C. Huntwork Sheetij Dutta Sarah V. Mudrak S. Munir Alam Scott Gregory Erik Jongert Margherita Coccia Fernando Ulloa-Montoya Ulrike Wille-Reece Georgia D. Tomaras S. Moses Dennison
author_sort	Kelly E. Seaton
title	Subclass and avidity of circumsporozoite protein specific antibodies associate with protection status against malaria infection
title_short	Subclass and avidity of circumsporozoite protein specific antibodies associate with protection status against malaria infection
title_full	Subclass and avidity of circumsporozoite protein specific antibodies associate with protection status against malaria infection
title_fullStr	Subclass and avidity of circumsporozoite protein specific antibodies associate with protection status against malaria infection
title_full_unstemmed	Subclass and avidity of circumsporozoite protein specific antibodies associate with protection status against malaria infection
title_sort	subclass and avidity of circumsporozoite protein specific antibodies associate with protection status against malaria infection
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/0219a60f06354a4495a0f6088c161287
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Subclass and avidity of circumsporozoite protein specific antibodies associate with protection status against malaria infection

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