Studying the effect of chloroquine on sporozoite-induced protection and immune responses in Plasmodium berghei malaria

Else M. Bijker, Krystelle Nganou-Makamdop, Geert Jan Van Gemert, Fidel P Zavala, Ian Cockburn, Robert W. Sauerwein

Research output: Contribution to journalArticle

Abstract

Background: Sporozoite immunization of animals and humans under a chemo-prophylactic cover of chloroquine (CPS-CQ) efficiently induces sterile protection against malaria. In humans, CPS-CQ is strikingly more efficient than immunization with radiation attenuated sporozoites (RAS), raising the hypothesis that this might be partially due to CQ. Chloroquine, an established anti-malarial drug, is also well known for its immune modulating properties including improvement of cross-presentation. The aim of this study was to investigate whether co-administration of CQ during sporozoite immunization improves cellular responses and protective efficacy in Plasmodium berghei models. Methods: A number of experiments in selected complimentary P. berghei murine models in Balb/cByJ and C57BL/6j mice was performed. First, the effect of CQ administration on the induction of protection and immune responses by RAS immunization was studied. Next, the effect of CQ on the induction of circumsporozoite (CS) protein-specific CD8+ T cells by immunization with P. berghei parasites expressing a mutant CS protein was investigated. Finally, a direct comparison of CPS-CQ to CPS with mefloquine (MQ), an anti-malarial with little known immune modulating effects, was performed. Results: When CQ was co-administered during immunization with graded numbers of RAS, this did not lead to an increase in frequencies of total memory CD8+ T cells or CS protein-specific CD8+ T cells. Also parasite-specific cytokine production and protection remained unaltered. Replacement of CQ by MQ for CPS immunization resulted in significantly reduced percentages of IFNγ producing memory T cells in the liver (p∈=∈0.01), but similar protection. Conclusions: This study does not provide evidence for a direct beneficial effect of CQ on the induction of sporozoite-induced immune responses and protection in P. berghei malaria models. Alternatively, the higher efficiency of CPS compared to RAS might be explained by an indirect effect of CQ through limiting blood-stage exposure after immunization or to increased antigen exposure and, therefore, improved breadth of the immune response.

Original languageEnglish (US)
Article number130
JournalMalaria Journal
Volume14
Issue number1
DOIs
StatePublished - Mar 26 2015

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Plasmodium malariae
Plasmodium berghei
Sporozoites
Chloroquine
Immunization
Radiation
Mefloquine
T-Lymphocytes
Antimalarials
Parasites
Cross-Priming
Mutant Proteins
Inbred C57BL Mouse
Malaria
Proteins
Cytokines
Antigens

Keywords

  • Chloroquine
  • Immunity
  • P. berghei
  • Protection
  • Sporozoite immunization
  • T cells

ASJC Scopus subject areas

  • Infectious Diseases
  • Parasitology

Cite this

Studying the effect of chloroquine on sporozoite-induced protection and immune responses in Plasmodium berghei malaria. / Bijker, Else M.; Nganou-Makamdop, Krystelle; Van Gemert, Geert Jan; Zavala, Fidel P; Cockburn, Ian; Sauerwein, Robert W.

In: Malaria Journal, Vol. 14, No. 1, 130, 26.03.2015.

Research output: Contribution to journalArticle

Bijker, Else M. ; Nganou-Makamdop, Krystelle ; Van Gemert, Geert Jan ; Zavala, Fidel P ; Cockburn, Ian ; Sauerwein, Robert W. / Studying the effect of chloroquine on sporozoite-induced protection and immune responses in Plasmodium berghei malaria. In: Malaria Journal. 2015 ; Vol. 14, No. 1.
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abstract = "Background: Sporozoite immunization of animals and humans under a chemo-prophylactic cover of chloroquine (CPS-CQ) efficiently induces sterile protection against malaria. In humans, CPS-CQ is strikingly more efficient than immunization with radiation attenuated sporozoites (RAS), raising the hypothesis that this might be partially due to CQ. Chloroquine, an established anti-malarial drug, is also well known for its immune modulating properties including improvement of cross-presentation. The aim of this study was to investigate whether co-administration of CQ during sporozoite immunization improves cellular responses and protective efficacy in Plasmodium berghei models. Methods: A number of experiments in selected complimentary P. berghei murine models in Balb/cByJ and C57BL/6j mice was performed. First, the effect of CQ administration on the induction of protection and immune responses by RAS immunization was studied. Next, the effect of CQ on the induction of circumsporozoite (CS) protein-specific CD8+ T cells by immunization with P. berghei parasites expressing a mutant CS protein was investigated. Finally, a direct comparison of CPS-CQ to CPS with mefloquine (MQ), an anti-malarial with little known immune modulating effects, was performed. Results: When CQ was co-administered during immunization with graded numbers of RAS, this did not lead to an increase in frequencies of total memory CD8+ T cells or CS protein-specific CD8+ T cells. Also parasite-specific cytokine production and protection remained unaltered. Replacement of CQ by MQ for CPS immunization resulted in significantly reduced percentages of IFNγ producing memory T cells in the liver (p∈=∈0.01), but similar protection. Conclusions: This study does not provide evidence for a direct beneficial effect of CQ on the induction of sporozoite-induced immune responses and protection in P. berghei malaria models. Alternatively, the higher efficiency of CPS compared to RAS might be explained by an indirect effect of CQ through limiting blood-stage exposure after immunization or to increased antigen exposure and, therefore, improved breadth of the immune response.",
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AU - Bijker, Else M.

AU - Nganou-Makamdop, Krystelle

AU - Van Gemert, Geert Jan

AU - Zavala, Fidel P

AU - Cockburn, Ian

AU - Sauerwein, Robert W.

PY - 2015/3/26

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N2 - Background: Sporozoite immunization of animals and humans under a chemo-prophylactic cover of chloroquine (CPS-CQ) efficiently induces sterile protection against malaria. In humans, CPS-CQ is strikingly more efficient than immunization with radiation attenuated sporozoites (RAS), raising the hypothesis that this might be partially due to CQ. Chloroquine, an established anti-malarial drug, is also well known for its immune modulating properties including improvement of cross-presentation. The aim of this study was to investigate whether co-administration of CQ during sporozoite immunization improves cellular responses and protective efficacy in Plasmodium berghei models. Methods: A number of experiments in selected complimentary P. berghei murine models in Balb/cByJ and C57BL/6j mice was performed. First, the effect of CQ administration on the induction of protection and immune responses by RAS immunization was studied. Next, the effect of CQ on the induction of circumsporozoite (CS) protein-specific CD8+ T cells by immunization with P. berghei parasites expressing a mutant CS protein was investigated. Finally, a direct comparison of CPS-CQ to CPS with mefloquine (MQ), an anti-malarial with little known immune modulating effects, was performed. Results: When CQ was co-administered during immunization with graded numbers of RAS, this did not lead to an increase in frequencies of total memory CD8+ T cells or CS protein-specific CD8+ T cells. Also parasite-specific cytokine production and protection remained unaltered. Replacement of CQ by MQ for CPS immunization resulted in significantly reduced percentages of IFNγ producing memory T cells in the liver (p∈=∈0.01), but similar protection. Conclusions: This study does not provide evidence for a direct beneficial effect of CQ on the induction of sporozoite-induced immune responses and protection in P. berghei malaria models. Alternatively, the higher efficiency of CPS compared to RAS might be explained by an indirect effect of CQ through limiting blood-stage exposure after immunization or to increased antigen exposure and, therefore, improved breadth of the immune response.

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