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Cited by 645Malaria Research and ControlBlood groups and transfusionHemoglobinopathies and Related Disorders

Parasite antigens on the infected red cell surface are targets for naturally acquired immunity to malaria

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Bull, Peter C., Lowe, Brett S., Kortok, Moses, Molyneux, Catherine S., Newbold, Christopher I., Marsh, Kevin·1998·Nature Medicine
DOI 10.1038/nm0398-358PMC PMC3836255
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Abstract

The feasibility of a malaria vaccine is supported by the fact that children in endemic areas develop naturally acquired immunity to disease. Development of disease immunity is characterized by a decrease in the frequency and severity of disease episodes over several years despite almost continuous infection, suggesting that immunity may develop through the acquisition of a repertoire of specific, protective antibodies directed against polymorphic target antigens. Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is a potentially important family of target antigens, because these proteins are inserted into the red cell surface and are prominently exposed and because they are highly polymorphic and undergo clonal antigenic variation, a mechanism of immune evasion maintained by a large family of var genes. In a large prospective study of Kenyan children, we have used the fact that anti-PfEMP1 antibodies agglutinate infected erythrocytes in a variant-specific manner, to show that the PfEMP1 variants expressed during episodes of clinical malaria were less likely to be recognized by the corresponding child's own preexisting antibody response than by that of children of the same age from the same community. In contrast, a heterologous parasite isolate was just as likely to be recognized. The apparent selective pressure exerted by established anti-PfEMP1 antibodies on infecting parasites supports the idea that such responses provide variant-specific protection against disease.

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Authors
Bull, P. C., Lowe, B. S., Kortok, M., Molyneux, C. S., Newbold, C. I., & Marsh, K.
Affiliations
  • Kenya Medical Research Institute (KE)
  • John Radcliffe Hospital (GB)
ORCID
Venue
Nature Medicine
Publisher
Springer Science and Business Media LLC
Published
1998-03
Volume
4
Issue
3
Pages
358-360
ISSN
  • 1078-8956 (ISSN-L)
  • 1546-170X
DOI
10.1038/nm0398-358
PMC
PMC3836255
OpenAlex
W2010795697
Cited by
645
References
1
Citations by year
2026: 1 · 2025: 9 · 2024: 14 · 2023: 13 · 2022: 10 · 2021: 12 · 2020: 7 · 2019: 25 · 2018: 20 · 2017: 28 · 2016: 32 · 2015: 21 · 2014: 25 · 2013: 18 · 2012: 19
FWCI
33.42
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
Wellcome Trust (631342, 061524)
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Malaria Research and Control
  • Health Sciences › Medicine › Hematology › Blood groups and transfusion
  • Health Sciences › Medicine › Genetics › Hemoglobinopathies and Related Disorders
Keywords
malaria, naturally acquired immunity, PfEMP1, erythrocyte membrane protein 1, Plasmodium falciparum, var genes, antigenic variation, antibody-mediated protection, malaria vaccine, children, clinical malaria episodes, immune evasion
MeSH terms
Age Factors, Agglutination Tests, Antibodies, Protozoan, Antibody Specificity, Antigenic Variation, Antigens, Protozoan, Blood Proteins, Child, Child, Preschool, Cross-Sectional Studies, Erythrocytes, Humans, Infant, Kenya, Population Surveillance, Prospective Studies, Protozoan Proteins, Odds Ratio, Malaria, Falciparum

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