Correlation of high levels of antibodies to multiple pre-erythrocytic Plasmodium falciparum antigens and protection from infection

Chandy John, Ann M. Moormann, Daniel C. Pregibon, Peter Odada Sumba, Marilyn M. McHugh, David L. Narum, David E. Lanar, Mark D. Schluchter, James W. Kazura

Research output: Contribution to journalArticle

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Abstract

High levels of antibodies to multiple antigens may be more strongly associated with protection from infection than antibodies to a single antigen. Antibody-associated protection against Plasmodium falciparum infection was assessed in a cohort of 68 adults living in an area of holoendemic malaria in Kenya. Antibodies to the pre-erythrocytic antigens circumsporozoite protein (CSP), liver-stage antigen-1 (LSA-1), thrombospondin-related adhesive protein (TRAP), and blood-stage antigens apical membrane antigen-1 (AMA-1), erythrocyte binding antigen-175 (EBA-175), and merozoite surface protein 1 (MSP-1) were tested. Peptides were used for CSP (NANP repeat) and LSA-1 (central repeat), and recombinant antigens were used for TRAP (aa D48-K394), AMA-1 (ectodomain, non-glycosylated), EBA-175 (non-glycosylated), and MSP-1 (MSP-119). Weekly microscopy testing for P. falciparum infection was performed over a 12-week period after drug-mediated clearance of P. falciparum parasitemia. Individuals with high levels of IgG antibodies (> 2 arbitrary units) to CSP, LSA-1, and TRAP had a 57% decrease in the risk of infection (95% confidence interval = 20-77%, P = 0.016). This decreased risk remained significant after adjustment for age, prior parasitemia, bed net use, sickle cell trait, and village of residence. In contrast, protection against infection did not correlate with high levels of IgG antibodies to blood-stage antigens or IgM antibodies to pre-erythrocytic or blood-stage antigens. High levels of IgG antibodies to CSP, LSA-1, and TRAP may be useful immune correlates of protection against P. falciparum infection in malaria-endemic populations.

Original languageEnglish (US)
Pages (from-to)222-228
Number of pages7
JournalAmerican Journal of Tropical Medicine and Hygiene
Volume73
Issue number1
StatePublished - Jul 2005
Externally publishedYes

Fingerprint

Plasmodium falciparum
Antigens
Antibodies
Infection
Malaria
Thrombospondin 1
Adhesives
Merozoite Surface Protein 1
Proteins
Parasitemia
Immunoglobulin G
Liver
Erythrocytes
Sickle Cell Trait
Thrombospondins
Membranes
Kenya
Immunoglobulin M
Blood Proteins
Microscopy

ASJC Scopus subject areas

  • Parasitology
  • Infectious Diseases

Cite this

John, C., Moormann, A. M., Pregibon, D. C., Sumba, P. O., McHugh, M. M., Narum, D. L., ... Kazura, J. W. (2005). Correlation of high levels of antibodies to multiple pre-erythrocytic Plasmodium falciparum antigens and protection from infection. American Journal of Tropical Medicine and Hygiene, 73(1), 222-228.

Correlation of high levels of antibodies to multiple pre-erythrocytic Plasmodium falciparum antigens and protection from infection. / John, Chandy; Moormann, Ann M.; Pregibon, Daniel C.; Sumba, Peter Odada; McHugh, Marilyn M.; Narum, David L.; Lanar, David E.; Schluchter, Mark D.; Kazura, James W.

In: American Journal of Tropical Medicine and Hygiene, Vol. 73, No. 1, 07.2005, p. 222-228.

Research output: Contribution to journalArticle

John, C, Moormann, AM, Pregibon, DC, Sumba, PO, McHugh, MM, Narum, DL, Lanar, DE, Schluchter, MD & Kazura, JW 2005, 'Correlation of high levels of antibodies to multiple pre-erythrocytic Plasmodium falciparum antigens and protection from infection', American Journal of Tropical Medicine and Hygiene, vol. 73, no. 1, pp. 222-228.
John, Chandy ; Moormann, Ann M. ; Pregibon, Daniel C. ; Sumba, Peter Odada ; McHugh, Marilyn M. ; Narum, David L. ; Lanar, David E. ; Schluchter, Mark D. ; Kazura, James W. / Correlation of high levels of antibodies to multiple pre-erythrocytic Plasmodium falciparum antigens and protection from infection. In: American Journal of Tropical Medicine and Hygiene. 2005 ; Vol. 73, No. 1. pp. 222-228.
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abstract = "High levels of antibodies to multiple antigens may be more strongly associated with protection from infection than antibodies to a single antigen. Antibody-associated protection against Plasmodium falciparum infection was assessed in a cohort of 68 adults living in an area of holoendemic malaria in Kenya. Antibodies to the pre-erythrocytic antigens circumsporozoite protein (CSP), liver-stage antigen-1 (LSA-1), thrombospondin-related adhesive protein (TRAP), and blood-stage antigens apical membrane antigen-1 (AMA-1), erythrocyte binding antigen-175 (EBA-175), and merozoite surface protein 1 (MSP-1) were tested. Peptides were used for CSP (NANP repeat) and LSA-1 (central repeat), and recombinant antigens were used for TRAP (aa D48-K394), AMA-1 (ectodomain, non-glycosylated), EBA-175 (non-glycosylated), and MSP-1 (MSP-119). Weekly microscopy testing for P. falciparum infection was performed over a 12-week period after drug-mediated clearance of P. falciparum parasitemia. Individuals with high levels of IgG antibodies (> 2 arbitrary units) to CSP, LSA-1, and TRAP had a 57{\%} decrease in the risk of infection (95{\%} confidence interval = 20-77{\%}, P = 0.016). This decreased risk remained significant after adjustment for age, prior parasitemia, bed net use, sickle cell trait, and village of residence. In contrast, protection against infection did not correlate with high levels of IgG antibodies to blood-stage antigens or IgM antibodies to pre-erythrocytic or blood-stage antigens. High levels of IgG antibodies to CSP, LSA-1, and TRAP may be useful immune correlates of protection against P. falciparum infection in malaria-endemic populations.",
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