Levels of plasma immunoglobulin G with specificity against the cysteine-rich interdomain regions of a semiconserved Plasmodium falciparum erythrocyte membrane protein 1, VAR4, predict protection against malarial anemia and febrile episodes

John P A Lusingu; Anja T R Jensen; Lasse S Vestergaard; Daniel T Minja; Michael B Dalgaard; Samwel Gesase; Bruno P Mmbando; Andrew Y Kitua; Martha M Lemnge; David Cavanagh; Lars Hviid; Thor G Theander

doi:10.1128/IAI.74.5.2867-2875.2006

Levels of plasma immunoglobulin G with specificity against the cysteine-rich interdomain regions of a semiconserved Plasmodium falciparum erythrocyte membrane protein 1, VAR4, predict protection against malarial anemia and febrile episodes

John P A Lusingu, Anja T R Jensen, Lasse S Vestergaard, Daniel T Minja, Michael B Dalgaard, Samwel Gesase, Bruno P Mmbando, Andrew Y Kitua, Martha M Lemnge, David Cavanagh, Lars Hviid, Thor G Theander

41 Citations (Scopus)

Abstract

Antibodies to variant surface antigen have been implicated as mediators of malaria immunity in studies measuring immunoglobulin G (IgG) binding to infected erythrocytes. Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is an important target for these antibodies, but no study has directly linked the presence of PfEMP1 antibodies in children to protection. We measured plasma IgG levels to the cysteine-rich interdomain region 1alpha (CIDR1alpha) of VAR4 (VAR4-CIDR1alpha), a member of a semiconserved PfEMP1 subfamily, by enzyme-linked immunosorbent assay in 561 Tanzanian individuals, who were monitored clinically for 7 months. The participants resided in Mkokola (a high-transmission village where malaria is holoendemic) or Kwamasimba (a moderate-transmission village). For comparison, plasma IgG levels to two merozoite surface protein 1 (MSP1) constructs, MSP1-19 and MSP1 block 2, and a control CIDR1 domain were measured. VAR4-CIDR1alpha antibodies were acquired at an earlier age in Mkokola than in Kwamasimba, but after the age of 10 years the levels were comparable in the two villages. After controlling for age and other covariates, the risk of having anemia at enrollment was reduced in VAR4-CIDR1alpha responders for Mkokola (adjusted odds ratio [AOR], 0.49; 95% confidence interval [CI], 0.29 to 0.88; P = 0.016) and Kwamasimba (AOR, 0.33; 95% CI, 0.16 to 0.68; P = 0.003) villages. The risk of developing malaria fever was reduced among individuals with a measurable VAR4-CIDR1alpha response from Mkokola village (AOR, 0.51; 95% CI, 0.29 to 0.89; P = 0.018) but not in Kwamasimba. Antibody levels to the MSP1 constructs and the control CIDR1alpha domain were not associated with morbidity protection. These data strengthen the concept of developing vaccines based on PfEMP1.

Original language	English
Journal	Infection and Immunity
Volume	74
Issue number	5
Pages (from-to)	2867-75
Number of pages	8
ISSN	0019-9567
DOIs	https://doi.org/10.1128/IAI.74.5.2867-2875.2006
Publication status	Published - 2006

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Lusingu, J. P. A., Jensen, A. T. R., Vestergaard, L. S., Minja, D. T., Dalgaard, M. B., Gesase, S., Mmbando, B. P., Kitua, A. Y., Lemnge, M. M., Cavanagh, D., Hviid, L., & Theander, T. G. (2006). Levels of plasma immunoglobulin G with specificity against the cysteine-rich interdomain regions of a semiconserved Plasmodium falciparum erythrocyte membrane protein 1, VAR4, predict protection against malarial anemia and febrile episodes. Infection and Immunity, 74(5), 2867-75. https://doi.org/10.1128/IAI.74.5.2867-2875.2006

Levels of plasma immunoglobulin G with specificity against the cysteine-rich interdomain regions of a semiconserved Plasmodium falciparum erythrocyte membrane protein 1, VAR4, predict protection against malarial anemia and febrile episodes. / Lusingu, John P A; Jensen, Anja T R; Vestergaard, Lasse S et al.

In: Infection and Immunity, Vol. 74, No. 5, 2006, p. 2867-75.

Research output: Contribution to journal › Journal article › Research › peer-review

Lusingu, JPA, Jensen, ATR, Vestergaard, LS, Minja, DT, Dalgaard, MB, Gesase, S, Mmbando, BP, Kitua, AY, Lemnge, MM, Cavanagh, D, Hviid, L & Theander, TG 2006, 'Levels of plasma immunoglobulin G with specificity against the cysteine-rich interdomain regions of a semiconserved Plasmodium falciparum erythrocyte membrane protein 1, VAR4, predict protection against malarial anemia and febrile episodes', Infection and Immunity, vol. 74, no. 5, pp. 2867-75. https://doi.org/10.1128/IAI.74.5.2867-2875.2006

Lusingu JPA, Jensen ATR, Vestergaard LS, Minja DT, Dalgaard MB, Gesase S et al. Levels of plasma immunoglobulin G with specificity against the cysteine-rich interdomain regions of a semiconserved Plasmodium falciparum erythrocyte membrane protein 1, VAR4, predict protection against malarial anemia and febrile episodes. Infection and Immunity. 2006;74(5):2867-75. doi: 10.1128/IAI.74.5.2867-2875.2006

Lusingu, John P A ; Jensen, Anja T R ; Vestergaard, Lasse S et al. / Levels of plasma immunoglobulin G with specificity against the cysteine-rich interdomain regions of a semiconserved Plasmodium falciparum erythrocyte membrane protein 1, VAR4, predict protection against malarial anemia and febrile episodes. In: Infection and Immunity. 2006 ; Vol. 74, No. 5. pp. 2867-75.

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title = "Levels of plasma immunoglobulin G with specificity against the cysteine-rich interdomain regions of a semiconserved Plasmodium falciparum erythrocyte membrane protein 1, VAR4, predict protection against malarial anemia and febrile episodes",

abstract = "Antibodies to variant surface antigen have been implicated as mediators of malaria immunity in studies measuring immunoglobulin G (IgG) binding to infected erythrocytes. Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is an important target for these antibodies, but no study has directly linked the presence of PfEMP1 antibodies in children to protection. We measured plasma IgG levels to the cysteine-rich interdomain region 1alpha (CIDR1alpha) of VAR4 (VAR4-CIDR1alpha), a member of a semiconserved PfEMP1 subfamily, by enzyme-linked immunosorbent assay in 561 Tanzanian individuals, who were monitored clinically for 7 months. The participants resided in Mkokola (a high-transmission village where malaria is holoendemic) or Kwamasimba (a moderate-transmission village). For comparison, plasma IgG levels to two merozoite surface protein 1 (MSP1) constructs, MSP1-19 and MSP1 block 2, and a control CIDR1 domain were measured. VAR4-CIDR1alpha antibodies were acquired at an earlier age in Mkokola than in Kwamasimba, but after the age of 10 years the levels were comparable in the two villages. After controlling for age and other covariates, the risk of having anemia at enrollment was reduced in VAR4-CIDR1alpha responders for Mkokola (adjusted odds ratio [AOR], 0.49; 95% confidence interval [CI], 0.29 to 0.88; P = 0.016) and Kwamasimba (AOR, 0.33; 95% CI, 0.16 to 0.68; P = 0.003) villages. The risk of developing malaria fever was reduced among individuals with a measurable VAR4-CIDR1alpha response from Mkokola village (AOR, 0.51; 95% CI, 0.29 to 0.89; P = 0.018) but not in Kwamasimba. Antibody levels to the MSP1 constructs and the control CIDR1alpha domain were not associated with morbidity protection. These data strengthen the concept of developing vaccines based on PfEMP1.",

author = "Lusingu, {John P A} and Jensen, {Anja T R} and Vestergaard, {Lasse S} and Minja, {Daniel T} and Dalgaard, {Michael B} and Samwel Gesase and Mmbando, {Bruno P} and Kitua, {Andrew Y} and Lemnge, {Martha M} and David Cavanagh and Lars Hviid and Theander, {Thor G}",

note = "Keywords: Adolescent; Adult; Anemia; Antibodies, Protozoan; Child; Child, Preschool; Fever; Hemoglobins; Humans; Immunoglobulin G; Infant; Infant, Newborn; Middle Aged; Peptide Fragments; Protein Structure, Tertiary; Protozoan Proteins",

year = "2006",

doi = "10.1128/IAI.74.5.2867-2875.2006",

language = "English",

volume = "74",

pages = "2867--75",

journal = "Infection and Immunity",

issn = "0019-9567",

publisher = "American Society for Microbiology",

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TY - JOUR

T1 - Levels of plasma immunoglobulin G with specificity against the cysteine-rich interdomain regions of a semiconserved Plasmodium falciparum erythrocyte membrane protein 1, VAR4, predict protection against malarial anemia and febrile episodes

AU - Lusingu, John P A

AU - Jensen, Anja T R

AU - Vestergaard, Lasse S

AU - Minja, Daniel T

AU - Dalgaard, Michael B

AU - Gesase, Samwel

AU - Mmbando, Bruno P

AU - Kitua, Andrew Y

AU - Lemnge, Martha M

AU - Cavanagh, David

AU - Hviid, Lars

AU - Theander, Thor G

N1 - Keywords: Adolescent; Adult; Anemia; Antibodies, Protozoan; Child; Child, Preschool; Fever; Hemoglobins; Humans; Immunoglobulin G; Infant; Infant, Newborn; Middle Aged; Peptide Fragments; Protein Structure, Tertiary; Protozoan Proteins

PY - 2006

Y1 - 2006

N2 - Antibodies to variant surface antigen have been implicated as mediators of malaria immunity in studies measuring immunoglobulin G (IgG) binding to infected erythrocytes. Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is an important target for these antibodies, but no study has directly linked the presence of PfEMP1 antibodies in children to protection. We measured plasma IgG levels to the cysteine-rich interdomain region 1alpha (CIDR1alpha) of VAR4 (VAR4-CIDR1alpha), a member of a semiconserved PfEMP1 subfamily, by enzyme-linked immunosorbent assay in 561 Tanzanian individuals, who were monitored clinically for 7 months. The participants resided in Mkokola (a high-transmission village where malaria is holoendemic) or Kwamasimba (a moderate-transmission village). For comparison, plasma IgG levels to two merozoite surface protein 1 (MSP1) constructs, MSP1-19 and MSP1 block 2, and a control CIDR1 domain were measured. VAR4-CIDR1alpha antibodies were acquired at an earlier age in Mkokola than in Kwamasimba, but after the age of 10 years the levels were comparable in the two villages. After controlling for age and other covariates, the risk of having anemia at enrollment was reduced in VAR4-CIDR1alpha responders for Mkokola (adjusted odds ratio [AOR], 0.49; 95% confidence interval [CI], 0.29 to 0.88; P = 0.016) and Kwamasimba (AOR, 0.33; 95% CI, 0.16 to 0.68; P = 0.003) villages. The risk of developing malaria fever was reduced among individuals with a measurable VAR4-CIDR1alpha response from Mkokola village (AOR, 0.51; 95% CI, 0.29 to 0.89; P = 0.018) but not in Kwamasimba. Antibody levels to the MSP1 constructs and the control CIDR1alpha domain were not associated with morbidity protection. These data strengthen the concept of developing vaccines based on PfEMP1.

AB - Antibodies to variant surface antigen have been implicated as mediators of malaria immunity in studies measuring immunoglobulin G (IgG) binding to infected erythrocytes. Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is an important target for these antibodies, but no study has directly linked the presence of PfEMP1 antibodies in children to protection. We measured plasma IgG levels to the cysteine-rich interdomain region 1alpha (CIDR1alpha) of VAR4 (VAR4-CIDR1alpha), a member of a semiconserved PfEMP1 subfamily, by enzyme-linked immunosorbent assay in 561 Tanzanian individuals, who were monitored clinically for 7 months. The participants resided in Mkokola (a high-transmission village where malaria is holoendemic) or Kwamasimba (a moderate-transmission village). For comparison, plasma IgG levels to two merozoite surface protein 1 (MSP1) constructs, MSP1-19 and MSP1 block 2, and a control CIDR1 domain were measured. VAR4-CIDR1alpha antibodies were acquired at an earlier age in Mkokola than in Kwamasimba, but after the age of 10 years the levels were comparable in the two villages. After controlling for age and other covariates, the risk of having anemia at enrollment was reduced in VAR4-CIDR1alpha responders for Mkokola (adjusted odds ratio [AOR], 0.49; 95% confidence interval [CI], 0.29 to 0.88; P = 0.016) and Kwamasimba (AOR, 0.33; 95% CI, 0.16 to 0.68; P = 0.003) villages. The risk of developing malaria fever was reduced among individuals with a measurable VAR4-CIDR1alpha response from Mkokola village (AOR, 0.51; 95% CI, 0.29 to 0.89; P = 0.018) but not in Kwamasimba. Antibody levels to the MSP1 constructs and the control CIDR1alpha domain were not associated with morbidity protection. These data strengthen the concept of developing vaccines based on PfEMP1.

U2 - 10.1128/IAI.74.5.2867-2875.2006

DO - 10.1128/IAI.74.5.2867-2875.2006

M3 - Journal article

C2 - 16622225

SN - 0019-9567

VL - 74

SP - 2867

EP - 2875

JO - Infection and Immunity

JF - Infection and Immunity

IS - 5

ER -