Antibody Biomarkers Associated with Sterile Protection Induced by Controlled Human Malaria Infection under Chloroquine Prophylaxis

ABSTRACT Immunization with sporozoites under chloroquine chemoprophylaxis (CPS) induces distinctly preerythrocytic and long-lasting sterile protection against homologous controlled human malaria infection (CHMI). To identify possible humoral immune correlates of protection, plasma samples were colle...

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Autores principales:	Joshua M. Obiero, Joseph J. Campo, Anja Scholzen, Arlo Randall, Else M. Bijker, Meta Roestenberg, Cornelus C. Hermsen, Andy Teng, Aarti Jain, D. Huw Davies, Robert W. Sauerwein, Philip L. Felgner
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	CHMI antibody malaria preerythrocytic immunity protein microarrays sterile protection Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/8e165887dd384f20b347b911c8b738d8
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spelling	oai:doaj.org-article:8e165887dd384f20b347b911c8b738d82021-11-15T15:22:04ZAntibody Biomarkers Associated with Sterile Protection Induced by Controlled Human Malaria Infection under Chloroquine Prophylaxis10.1128/mSphereDirect.00027-192379-5042https://doaj.org/article/8e165887dd384f20b347b911c8b738d82019-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphereDirect.00027-19https://doaj.org/toc/2379-5042ABSTRACT Immunization with sporozoites under chloroquine chemoprophylaxis (CPS) induces distinctly preerythrocytic and long-lasting sterile protection against homologous controlled human malaria infection (CHMI). To identify possible humoral immune correlates of protection, plasma samples were collected from 38 CPS-immunized Dutch volunteers for analysis using a whole Plasmodium falciparum proteome microarray with 7,455 full-length or segmented protein features displaying about 91% of the total P. falciparum proteome. We identified 548 reactive antigens representing 483 unique proteins. Using the breadth of antibody responses for each subject in a mixture-model algorithm, we observed a trimodal pattern, with distinct groups of 16 low responders, 19 medium responders, and 3 high responders. Fifteen out of 16 low responders, 12 of the 19 medium responders, and 3 out of 3 high responders were fully protected from a challenge infection. In the medium-responder group, we identified six novel antigens associated with protection (area under the curve [AUC] value of ≥0.75; P < 0.05) and six other antigens that were specifically increased in nonprotected volunteers (AUC value of ≤0.25; P < 0.05). When used in combination, the multiantigen classifier predicts CPS-induced protective efficacy with 83% sensitivity and 88% specificity. The antibody response patterns characterized in this study represent surrogate markers that may provide rational guidance for clinical vaccine development. IMPORTANCE Infection by Plasmodium parasites has been a major cause of mortality and morbidity in humans for thousands of years. Despite the considerable reduction of deaths, according to the WHO, over 5 billion people are still at risk, with about 216 million worldwide cases occurring in 2016. More compelling, 15 countries in sub-Saharan Africa bore 80% of the worldwide malaria burden. Complete eradication has been challenging, and the development of an affordable and effective vaccine will go a long way in achieving elimination. However, identifying vaccine candidate targets has been difficult. In the present study, we use a highly effective immunization protocol that confers long-lasting sterile immunity in combination with a whole P. falciparum proteome microarray to identify antibody responses associated with protection. This study characterizes a novel antibody profile associated with sterile protective immunity and trimodal humoral responses that sheds light on the possible mechanism of CPS-induced immunity against P. falciparum parasites.Joshua M. ObieroJoseph J. CampoAnja ScholzenArlo RandallElse M. BijkerMeta RoestenbergCornelus C. HermsenAndy TengAarti JainD. Huw DaviesRobert W. SauerweinPhilip L. FelgnerAmerican Society for MicrobiologyarticleCHMIantibodymalariapreerythrocytic immunityprotein microarrayssterile protectionMicrobiologyQR1-502ENmSphere, Vol 4, Iss 1 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	CHMI antibody malaria preerythrocytic immunity protein microarrays sterile protection Microbiology QR1-502
spellingShingle	CHMI antibody malaria preerythrocytic immunity protein microarrays sterile protection Microbiology QR1-502 Joshua M. Obiero Joseph J. Campo Anja Scholzen Arlo Randall Else M. Bijker Meta Roestenberg Cornelus C. Hermsen Andy Teng Aarti Jain D. Huw Davies Robert W. Sauerwein Philip L. Felgner Antibody Biomarkers Associated with Sterile Protection Induced by Controlled Human Malaria Infection under Chloroquine Prophylaxis
description	ABSTRACT Immunization with sporozoites under chloroquine chemoprophylaxis (CPS) induces distinctly preerythrocytic and long-lasting sterile protection against homologous controlled human malaria infection (CHMI). To identify possible humoral immune correlates of protection, plasma samples were collected from 38 CPS-immunized Dutch volunteers for analysis using a whole Plasmodium falciparum proteome microarray with 7,455 full-length or segmented protein features displaying about 91% of the total P. falciparum proteome. We identified 548 reactive antigens representing 483 unique proteins. Using the breadth of antibody responses for each subject in a mixture-model algorithm, we observed a trimodal pattern, with distinct groups of 16 low responders, 19 medium responders, and 3 high responders. Fifteen out of 16 low responders, 12 of the 19 medium responders, and 3 out of 3 high responders were fully protected from a challenge infection. In the medium-responder group, we identified six novel antigens associated with protection (area under the curve [AUC] value of ≥0.75; P < 0.05) and six other antigens that were specifically increased in nonprotected volunteers (AUC value of ≤0.25; P < 0.05). When used in combination, the multiantigen classifier predicts CPS-induced protective efficacy with 83% sensitivity and 88% specificity. The antibody response patterns characterized in this study represent surrogate markers that may provide rational guidance for clinical vaccine development. IMPORTANCE Infection by Plasmodium parasites has been a major cause of mortality and morbidity in humans for thousands of years. Despite the considerable reduction of deaths, according to the WHO, over 5 billion people are still at risk, with about 216 million worldwide cases occurring in 2016. More compelling, 15 countries in sub-Saharan Africa bore 80% of the worldwide malaria burden. Complete eradication has been challenging, and the development of an affordable and effective vaccine will go a long way in achieving elimination. However, identifying vaccine candidate targets has been difficult. In the present study, we use a highly effective immunization protocol that confers long-lasting sterile immunity in combination with a whole P. falciparum proteome microarray to identify antibody responses associated with protection. This study characterizes a novel antibody profile associated with sterile protective immunity and trimodal humoral responses that sheds light on the possible mechanism of CPS-induced immunity against P. falciparum parasites.
format	article
author	Joshua M. Obiero Joseph J. Campo Anja Scholzen Arlo Randall Else M. Bijker Meta Roestenberg Cornelus C. Hermsen Andy Teng Aarti Jain D. Huw Davies Robert W. Sauerwein Philip L. Felgner
author_facet	Joshua M. Obiero Joseph J. Campo Anja Scholzen Arlo Randall Else M. Bijker Meta Roestenberg Cornelus C. Hermsen Andy Teng Aarti Jain D. Huw Davies Robert W. Sauerwein Philip L. Felgner
author_sort	Joshua M. Obiero
title	Antibody Biomarkers Associated with Sterile Protection Induced by Controlled Human Malaria Infection under Chloroquine Prophylaxis
title_short	Antibody Biomarkers Associated with Sterile Protection Induced by Controlled Human Malaria Infection under Chloroquine Prophylaxis
title_full	Antibody Biomarkers Associated with Sterile Protection Induced by Controlled Human Malaria Infection under Chloroquine Prophylaxis
title_fullStr	Antibody Biomarkers Associated with Sterile Protection Induced by Controlled Human Malaria Infection under Chloroquine Prophylaxis
title_full_unstemmed	Antibody Biomarkers Associated with Sterile Protection Induced by Controlled Human Malaria Infection under Chloroquine Prophylaxis
title_sort	antibody biomarkers associated with sterile protection induced by controlled human malaria infection under chloroquine prophylaxis
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/8e165887dd384f20b347b911c8b738d8
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Antibody Biomarkers Associated with Sterile Protection Induced by Controlled Human Malaria Infection under Chloroquine Prophylaxis

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