Antibody Biomarkers Associated with Sterile Protection Induced by Controlled Human Malaria Infection under Chloroquine Prophylaxis
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...
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doaj-fc799479af1a4be1b1a8f77e77a05e042020-11-25T02:14:52ZengAmerican Society for MicrobiologymSphere2379-50422019-02-0141e00027-1910.1128/mSphereDirect.00027-19Antibody Biomarkers Associated with Sterile Protection Induced by Controlled Human Malaria Infection under Chloroquine ProphylaxisJoshua M. ObieroJoseph J. CampoAnja ScholzenArlo RandallElse M. BijkerMeta RoestenbergCornelus C. HermsenAndy TengAarti JainD. Huw DaviesRobert W. SauerweinPhilip L. FelgnerInfection 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.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.https://doi.org/10.1128/mSphereDirect.00027-19CHMIantibodymalariapreerythrocytic immunityprotein microarrayssterile protectionvaccines |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
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 |
spellingShingle |
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 mSphere CHMI antibody malaria preerythrocytic immunity protein microarrays sterile protection vaccines |
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 |
series |
mSphere |
issn |
2379-5042 |
publishDate |
2019-02-01 |
description |
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.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. |
topic |
CHMI antibody malaria preerythrocytic immunity protein microarrays sterile protection vaccines |
url |
https://doi.org/10.1128/mSphereDirect.00027-19 |
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