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...
Ausführliche Beschreibung
Autor*in: |
Joshua M. Obiero [verfasserIn] Joseph J. Campo [verfasserIn] Anja Scholzen [verfasserIn] Arlo Randall [verfasserIn] Else M. Bijker [verfasserIn] Meta Roestenberg [verfasserIn] Cornelus C. Hermsen [verfasserIn] Andy Teng [verfasserIn] Aarti Jain [verfasserIn] D. Huw Davies [verfasserIn] Robert W. Sauerwein [verfasserIn] Philip L. Felgner [verfasserIn] |
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E-Artikel |
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Sprache: |
Englisch |
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2019 |
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Übergeordnetes Werk: |
In: mSphere - American Society for Microbiology, 2016, 4(2019), 1 |
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Übergeordnetes Werk: |
volume:4 ; year:2019 ; number:1 |
Links: |
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DOI / URN: |
10.1128/mSphereDirect.00027-19 |
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Katalog-ID: |
DOAJ061081612 |
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520 | |a 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. | ||
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10.1128/mSphereDirect.00027-19 doi (DE-627)DOAJ061081612 (DE-599)DOAJ8e165887dd384f20b347b911c8b738d8 DE-627 ger DE-627 rakwb eng QR1-502 Joshua M. Obiero verfasserin aut Antibody Biomarkers Associated with Sterile Protection Induced by Controlled Human Malaria Infection under Chloroquine Prophylaxis 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. CHMI antibody malaria preerythrocytic immunity protein microarrays sterile protection Microbiology Joseph J. Campo verfasserin aut Anja Scholzen verfasserin aut Arlo Randall verfasserin aut Else M. Bijker verfasserin aut Meta Roestenberg verfasserin aut Cornelus C. Hermsen verfasserin aut Andy Teng verfasserin aut Aarti Jain verfasserin aut D. Huw Davies verfasserin aut Robert W. Sauerwein verfasserin aut Philip L. Felgner verfasserin aut In mSphere American Society for Microbiology, 2016 4(2019), 1 (DE-627)845748807 (DE-600)2844248-9 23795042 nnns volume:4 year:2019 number:1 https://doi.org/10.1128/mSphereDirect.00027-19 kostenfrei https://doaj.org/article/8e165887dd384f20b347b911c8b738d8 kostenfrei https://journals.asm.org/doi/10.1128/mSphereDirect.00027-19 kostenfrei https://doaj.org/toc/2379-5042 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 4 2019 1 |
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10.1128/mSphereDirect.00027-19 doi (DE-627)DOAJ061081612 (DE-599)DOAJ8e165887dd384f20b347b911c8b738d8 DE-627 ger DE-627 rakwb eng QR1-502 Joshua M. Obiero verfasserin aut Antibody Biomarkers Associated with Sterile Protection Induced by Controlled Human Malaria Infection under Chloroquine Prophylaxis 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. CHMI antibody malaria preerythrocytic immunity protein microarrays sterile protection Microbiology Joseph J. Campo verfasserin aut Anja Scholzen verfasserin aut Arlo Randall verfasserin aut Else M. Bijker verfasserin aut Meta Roestenberg verfasserin aut Cornelus C. Hermsen verfasserin aut Andy Teng verfasserin aut Aarti Jain verfasserin aut D. Huw Davies verfasserin aut Robert W. Sauerwein verfasserin aut Philip L. Felgner verfasserin aut In mSphere American Society for Microbiology, 2016 4(2019), 1 (DE-627)845748807 (DE-600)2844248-9 23795042 nnns volume:4 year:2019 number:1 https://doi.org/10.1128/mSphereDirect.00027-19 kostenfrei https://doaj.org/article/8e165887dd384f20b347b911c8b738d8 kostenfrei https://journals.asm.org/doi/10.1128/mSphereDirect.00027-19 kostenfrei https://doaj.org/toc/2379-5042 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 4 2019 1 |
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10.1128/mSphereDirect.00027-19 doi (DE-627)DOAJ061081612 (DE-599)DOAJ8e165887dd384f20b347b911c8b738d8 DE-627 ger DE-627 rakwb eng QR1-502 Joshua M. Obiero verfasserin aut Antibody Biomarkers Associated with Sterile Protection Induced by Controlled Human Malaria Infection under Chloroquine Prophylaxis 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. CHMI antibody malaria preerythrocytic immunity protein microarrays sterile protection Microbiology Joseph J. Campo verfasserin aut Anja Scholzen verfasserin aut Arlo Randall verfasserin aut Else M. Bijker verfasserin aut Meta Roestenberg verfasserin aut Cornelus C. Hermsen verfasserin aut Andy Teng verfasserin aut Aarti Jain verfasserin aut D. Huw Davies verfasserin aut Robert W. Sauerwein verfasserin aut Philip L. Felgner verfasserin aut In mSphere American Society for Microbiology, 2016 4(2019), 1 (DE-627)845748807 (DE-600)2844248-9 23795042 nnns volume:4 year:2019 number:1 https://doi.org/10.1128/mSphereDirect.00027-19 kostenfrei https://doaj.org/article/8e165887dd384f20b347b911c8b738d8 kostenfrei https://journals.asm.org/doi/10.1128/mSphereDirect.00027-19 kostenfrei https://doaj.org/toc/2379-5042 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 4 2019 1 |
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10.1128/mSphereDirect.00027-19 doi (DE-627)DOAJ061081612 (DE-599)DOAJ8e165887dd384f20b347b911c8b738d8 DE-627 ger DE-627 rakwb eng QR1-502 Joshua M. Obiero verfasserin aut Antibody Biomarkers Associated with Sterile Protection Induced by Controlled Human Malaria Infection under Chloroquine Prophylaxis 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. CHMI antibody malaria preerythrocytic immunity protein microarrays sterile protection Microbiology Joseph J. Campo verfasserin aut Anja Scholzen verfasserin aut Arlo Randall verfasserin aut Else M. Bijker verfasserin aut Meta Roestenberg verfasserin aut Cornelus C. Hermsen verfasserin aut Andy Teng verfasserin aut Aarti Jain verfasserin aut D. Huw Davies verfasserin aut Robert W. Sauerwein verfasserin aut Philip L. Felgner verfasserin aut In mSphere American Society for Microbiology, 2016 4(2019), 1 (DE-627)845748807 (DE-600)2844248-9 23795042 nnns volume:4 year:2019 number:1 https://doi.org/10.1128/mSphereDirect.00027-19 kostenfrei https://doaj.org/article/8e165887dd384f20b347b911c8b738d8 kostenfrei https://journals.asm.org/doi/10.1128/mSphereDirect.00027-19 kostenfrei https://doaj.org/toc/2379-5042 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 4 2019 1 |
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Antibody Biomarkers Associated with Sterile Protection Induced by Controlled Human Malaria Infection under Chloroquine Prophylaxis |
abstract |
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. |
abstractGer |
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. |
abstract_unstemmed |
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. |
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container_issue |
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title_short |
Antibody Biomarkers Associated with Sterile Protection Induced by Controlled Human Malaria Infection under Chloroquine Prophylaxis |
url |
https://doi.org/10.1128/mSphereDirect.00027-19 https://doaj.org/article/8e165887dd384f20b347b911c8b738d8 https://journals.asm.org/doi/10.1128/mSphereDirect.00027-19 https://doaj.org/toc/2379-5042 |
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author2 |
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 |
author2Str |
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 |
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doi_str |
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callnumber-a |
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up_date |
2024-07-03T18:43:34.171Z |
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