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Serologic responses to the PfEMP1 DBL-CIDR head structure may be a better indicator of malaria exposure than those to the DBL-α tag

  • Stucke, Emily M.1
  • Niangaly, Amadou2
  • Berry, Andrea A.1
  • Bailey, Jason A.3
  • Coulibaly, Drissa2
  • Ouattara, Amed1
  • Lyke, Kirsten E.1
  • Laurens, Matthew B.1
  • Dara, Antoine2
  • Adams, Matthew1
  • Pablo, Jozelyn4
  • Jasinskas, Algis4
  • Nakajima, Rie4
  • Zhou, Albert E.1
  • Agrawal, Sonia1
  • Friedman-Klabanoff, DeAnna J.1
  • Takala-Harrison, Shannon1
  • Kouriba, Bourema2
  • Kone, Abdoulaye K.2
  • Rowe, J. Alexandra5
  • And 5 more
  • 1 University of Maryland School of Medicine, Malaria Research Program, Center for Vaccine Development and Global Health, Baltimore, MD, USA , Baltimore (United States)
  • 2 University of Science, Techniques and Technologies of Bamako, Malaria Research and Training Center, Bamako, Mali , Bamako (Mali)
  • 3 The EMMES Corporation, Rockville, MD, USA , Rockville (United States)
  • 4 University of California, Division of Infectious Diseases, Department of Medicine, Irvine, CA, USA , Irvine (United States)
  • 5 University of Edinburgh, Centre for Immunity, Infection and Evolution, Institute of Immunology and Infection Research, School of Biological Sciences, Edinburgh, UK , Edinburgh (United Kingdom)
  • 6 Duke University, Duke Global Health Institute, Durham, NC, USA , Durham (United States)
Published Article
Malaria Journal
Springer (Biomed Central Ltd.)
Publication Date
Aug 13, 2019
DOI: 10.1186/s12936-019-2905-9
Springer Nature


BackgroundPlasmodium falciparum erythrocyte membrane protein-1 (PfEMP1) antigens play a critical role in host immune evasion. Serologic responses to these antigens have been associated with protection from clinical malaria, suggesting that antibodies to PfEMP1 antigens may contribute to natural immunity. The first N-terminal constitutive domain in a PfEMP1 is the Duffy binding-like alpha (DBL-α) domain, which contains a 300 to 400 base pair region unique to each particular protein (the DBL-α “tag”). This DBL-α tag has been used as a marker of PfEMP1 diversity and serologic responses in malaria-exposed populations. In this study, using sera from a malaria-endemic region, responses to DBL-α tags were compared to responses to the corresponding entire DBL-α domain (or “parent” domain) coupled with the succeeding cysteine-rich interdomain region (CIDR).MethodsA protein microarray populated with DBL-α tags, the parent DBL-CIDR head structures, and downstream PfEMP1 protein fragments was probed with sera from Malian children (aged 1 to 6 years) and adults from the control arms of apical membrane antigen 1 (AMA1) vaccine clinical trials before and during a malaria transmission season. Serological responses to the DBL-α tag and the DBL-CIDR head structure were measured and compared in children and adults, and throughout the season.ResultsMalian serologic responses to a PfEMP1’s DBL-α tag region did not correlate with seasonal malaria exposure, or with responses to the parent DBL-CIDR head structure in either children or adults. Parent DBL-CIDR head structures were better indicators of malaria exposure.ConclusionsLarger PfEMP1 domains may be better indicators of malaria exposure than short, variable PfEMP1 fragments such as DBL-α tags. PfEMP1 head structures that include conserved sequences appear particularly well suited for study as serologic predictors of malaria exposure.

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