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Editor's Pick Research Article | Clinical Science and Epidemiology

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

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
Marcela F. Pasetti, Editor
Joshua M. Obiero
aVaccine Research and Development Center, Department of Physiology and Biophysics, University of California, Irvine, Irvine, California, USA
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  • ORCID record for Joshua M. Obiero
Joseph J. Campo
cAntigen Discovery, Inc., Irvine, California, USA
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Anja Scholzen
bRadboud University Medical Center, Department of Medical Microbiology, Nijmegen, The Netherlands
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Arlo Randall
cAntigen Discovery, Inc., Irvine, California, USA
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Else M. Bijker
bRadboud University Medical Center, Department of Medical Microbiology, Nijmegen, The Netherlands
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Meta Roestenberg
bRadboud University Medical Center, Department of Medical Microbiology, Nijmegen, The Netherlands
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Cornelus C. Hermsen
bRadboud University Medical Center, Department of Medical Microbiology, Nijmegen, The Netherlands
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Andy Teng
cAntigen Discovery, Inc., Irvine, California, USA
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Aarti Jain
aVaccine Research and Development Center, Department of Physiology and Biophysics, University of California, Irvine, Irvine, California, USA
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D. Huw Davies
aVaccine Research and Development Center, Department of Physiology and Biophysics, University of California, Irvine, Irvine, California, USA
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Robert W. Sauerwein
bRadboud University Medical Center, Department of Medical Microbiology, Nijmegen, The Netherlands
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Philip L. Felgner
aVaccine Research and Development Center, Department of Physiology and Biophysics, University of California, Irvine, Irvine, California, USA
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Marcela F. Pasetti
University of Maryland School of Medicine
Roles: Editor
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Lars Hviid
University of Copenhagen
Roles: Solicited external reviewer
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Anne Frosch
University of Minnesota
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DOI: 10.1128/mSphereDirect.00027-19
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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.

FOOTNOTES

    • Received January 11, 2019.
    • Accepted January 21, 2019.
  • This paper was submitted via the mSphereDirect™ pathway.

  • Copyright © 2019 Obiero et al.

This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

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Antibody Biomarkers Associated with Sterile Protection Induced by Controlled Human Malaria Infection under Chloroquine Prophylaxis
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
mSphere Feb 2019, 4 (1) e00027-19; DOI: 10.1128/mSphereDirect.00027-19

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Antibody Biomarkers Associated with Sterile Protection Induced by Controlled Human Malaria Infection under Chloroquine Prophylaxis
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
mSphere Feb 2019, 4 (1) e00027-19; DOI: 10.1128/mSphereDirect.00027-19
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KEYWORDS

CHMI
antibody
malaria
preerythrocytic immunity
protein microarrays
sterile protection
vaccines

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