Antibody responses to antigenic targets of recent exposure are associated with low-density parasitemia in controlled human plasmodium falciparuminfections

Lotus L. Van Den Hoogen, Jona Walk, Tate Oulton, Isaie J. Reuling, Linda Reiling, James G. Beeson, Ross L. Coppel, Susheel K. Singh, Simon J. Draper, Teun Bousema, Chris Drakeley, Robert Sauerwein, Kevin K.A. Tetteh

Research output: Contribution to journalArticleResearchpeer-review

Abstract

The majority of malaria infections in low transmission settings remain undetectable by conventional diagnostics. A powerful model to identify antibody responses that allow accurate detection of recent exposure to low-density infections is controlled human malaria infection (CHMI) studies in which healthy volunteers are infected with the Plasmodium parasite. We aimed to evaluate antibody responses in malaria-naïve volunteers exposed to a single CHMI using a custom-made protein microarray. All participants developed a blood-stage infection with peak parasite densities up to 100 parasites/μl in the majority of participants (50/54), while the remaining four participants had peak densities between 100 and 200 parasites/μl. There was a strong correlation between parasite density and antibody responses associated with the most reactive blood-stage targets 1 month after CHMI (Etramp 5, GLURP-R2, MSP4 and MSP1-19; Spearman's ρ = 0.82, p < 0.001). Most volunteers developed antibodies against a potential marker of recent exposure: Etramp 5 (37/45, 82%). Our findings justify validation in endemic populations to define a minimum set of antigens needed to detect exposure to natural low-density infections.

Original languageEnglish
Article number03300
Number of pages11
JournalFrontiers in Microbiology
Volume10
DOIs
Publication statusPublished - 16 Jan 2019

Keywords

  • antibodies
  • controlled human malaria infection (CHMI)
  • exposure
  • malaria
  • sero-epidemiology
  • sero-surveillance

Cite this

Van Den Hoogen, Lotus L. ; Walk, Jona ; Oulton, Tate ; Reuling, Isaie J. ; Reiling, Linda ; Beeson, James G. ; Coppel, Ross L. ; Singh, Susheel K. ; Draper, Simon J. ; Bousema, Teun ; Drakeley, Chris ; Sauerwein, Robert ; Tetteh, Kevin K.A. / Antibody responses to antigenic targets of recent exposure are associated with low-density parasitemia in controlled human plasmodium falciparuminfections. In: Frontiers in Microbiology. 2019 ; Vol. 10.
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abstract = "The majority of malaria infections in low transmission settings remain undetectable by conventional diagnostics. A powerful model to identify antibody responses that allow accurate detection of recent exposure to low-density infections is controlled human malaria infection (CHMI) studies in which healthy volunteers are infected with the Plasmodium parasite. We aimed to evaluate antibody responses in malaria-na{\"i}ve volunteers exposed to a single CHMI using a custom-made protein microarray. All participants developed a blood-stage infection with peak parasite densities up to 100 parasites/μl in the majority of participants (50/54), while the remaining four participants had peak densities between 100 and 200 parasites/μl. There was a strong correlation between parasite density and antibody responses associated with the most reactive blood-stage targets 1 month after CHMI (Etramp 5, GLURP-R2, MSP4 and MSP1-19; Spearman's ρ = 0.82, p < 0.001). Most volunteers developed antibodies against a potential marker of recent exposure: Etramp 5 (37/45, 82{\%}). Our findings justify validation in endemic populations to define a minimum set of antigens needed to detect exposure to natural low-density infections.",
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author = "{Van Den Hoogen}, {Lotus L.} and Jona Walk and Tate Oulton and Reuling, {Isaie J.} and Linda Reiling and Beeson, {James G.} and Coppel, {Ross L.} and Singh, {Susheel K.} and Draper, {Simon J.} and Teun Bousema and Chris Drakeley and Robert Sauerwein and Tetteh, {Kevin K.A.}",
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doi = "10.3389/fmicb.2018.03300",
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Van Den Hoogen, LL, Walk, J, Oulton, T, Reuling, IJ, Reiling, L, Beeson, JG, Coppel, RL, Singh, SK, Draper, SJ, Bousema, T, Drakeley, C, Sauerwein, R & Tetteh, KKA 2019, 'Antibody responses to antigenic targets of recent exposure are associated with low-density parasitemia in controlled human plasmodium falciparuminfections' Frontiers in Microbiology, vol. 10, 03300. https://doi.org/10.3389/fmicb.2018.03300

Antibody responses to antigenic targets of recent exposure are associated with low-density parasitemia in controlled human plasmodium falciparuminfections. / Van Den Hoogen, Lotus L.; Walk, Jona; Oulton, Tate; Reuling, Isaie J.; Reiling, Linda; Beeson, James G.; Coppel, Ross L.; Singh, Susheel K.; Draper, Simon J.; Bousema, Teun; Drakeley, Chris; Sauerwein, Robert; Tetteh, Kevin K.A.

In: Frontiers in Microbiology, Vol. 10, 03300, 16.01.2019.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Antibody responses to antigenic targets of recent exposure are associated with low-density parasitemia in controlled human plasmodium falciparuminfections

AU - Van Den Hoogen, Lotus L.

AU - Walk, Jona

AU - Oulton, Tate

AU - Reuling, Isaie J.

AU - Reiling, Linda

AU - Beeson, James G.

AU - Coppel, Ross L.

AU - Singh, Susheel K.

AU - Draper, Simon J.

AU - Bousema, Teun

AU - Drakeley, Chris

AU - Sauerwein, Robert

AU - Tetteh, Kevin K.A.

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N2 - The majority of malaria infections in low transmission settings remain undetectable by conventional diagnostics. A powerful model to identify antibody responses that allow accurate detection of recent exposure to low-density infections is controlled human malaria infection (CHMI) studies in which healthy volunteers are infected with the Plasmodium parasite. We aimed to evaluate antibody responses in malaria-naïve volunteers exposed to a single CHMI using a custom-made protein microarray. All participants developed a blood-stage infection with peak parasite densities up to 100 parasites/μl in the majority of participants (50/54), while the remaining four participants had peak densities between 100 and 200 parasites/μl. There was a strong correlation between parasite density and antibody responses associated with the most reactive blood-stage targets 1 month after CHMI (Etramp 5, GLURP-R2, MSP4 and MSP1-19; Spearman's ρ = 0.82, p < 0.001). Most volunteers developed antibodies against a potential marker of recent exposure: Etramp 5 (37/45, 82%). Our findings justify validation in endemic populations to define a minimum set of antigens needed to detect exposure to natural low-density infections.

AB - The majority of malaria infections in low transmission settings remain undetectable by conventional diagnostics. A powerful model to identify antibody responses that allow accurate detection of recent exposure to low-density infections is controlled human malaria infection (CHMI) studies in which healthy volunteers are infected with the Plasmodium parasite. We aimed to evaluate antibody responses in malaria-naïve volunteers exposed to a single CHMI using a custom-made protein microarray. All participants developed a blood-stage infection with peak parasite densities up to 100 parasites/μl in the majority of participants (50/54), while the remaining four participants had peak densities between 100 and 200 parasites/μl. There was a strong correlation between parasite density and antibody responses associated with the most reactive blood-stage targets 1 month after CHMI (Etramp 5, GLURP-R2, MSP4 and MSP1-19; Spearman's ρ = 0.82, p < 0.001). Most volunteers developed antibodies against a potential marker of recent exposure: Etramp 5 (37/45, 82%). Our findings justify validation in endemic populations to define a minimum set of antigens needed to detect exposure to natural low-density infections.

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KW - exposure

KW - malaria

KW - sero-epidemiology

KW - sero-surveillance

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U2 - 10.3389/fmicb.2018.03300

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