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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.
Malar J 2019; 18(1):273MJ

Abstract

BACKGROUND

Plasmodium 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).

METHODS

A 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.

RESULTS

Malian 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.

CONCLUSIONS

Larger 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.

Authors+Show Affiliations

Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, USA.Malaria Research and Training Center, University of Science, Techniques and Technologies of Bamako, Bamako, Mali.Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, USA.The EMMES Corporation, Rockville, MD, USA.Malaria Research and Training Center, University of Science, Techniques and Technologies of Bamako, Bamako, Mali.Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, USA.Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, USA.Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, USA.Malaria Research and Training Center, University of Science, Techniques and Technologies of Bamako, Bamako, Mali.Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, USA.Division of Infectious Diseases, Department of Medicine, University of California, Irvine, CA, USA.Division of Infectious Diseases, Department of Medicine, University of California, Irvine, CA, USA.Division of Infectious Diseases, Department of Medicine, University of California, Irvine, CA, USA.Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, USA.Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, USA.Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, USA.Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, USA.Malaria Research and Training Center, University of Science, Techniques and Technologies of Bamako, Bamako, Mali.Malaria Research and Training Center, University of Science, Techniques and Technologies of Bamako, Bamako, Mali.Centre for Immunity, Infection and Evolution, Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh, UK.Malaria Research and Training Center, University of Science, Techniques and Technologies of Bamako, Bamako, Mali.Division of Infectious Diseases, Department of Medicine, University of California, Irvine, CA, USA.Malaria Research and Training Center, University of Science, Techniques and Technologies of Bamako, Bamako, Mali.Duke Global Health Institute, Duke University, Durham, NC, USA.Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, USA. mtravass@som.umaryland.edu.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31409360

Citation

Stucke, Emily M., et al. "Serologic Responses to the PfEMP1 DBL-CIDR Head Structure May Be a Better Indicator of Malaria Exposure Than Those to the DBL-α Tag." Malaria Journal, vol. 18, no. 1, 2019, p. 273.
Stucke EM, Niangaly A, Berry AA, et al. Serologic responses to the PfEMP1 DBL-CIDR head structure may be a better indicator of malaria exposure than those to the DBL-α tag. Malar J. 2019;18(1):273.
Stucke, E. M., Niangaly, A., Berry, A. A., Bailey, J. A., Coulibaly, D., Ouattara, A., ... Travassos, M. A. (2019). Serologic responses to the PfEMP1 DBL-CIDR head structure may be a better indicator of malaria exposure than those to the DBL-α tag. Malaria Journal, 18(1), p. 273. doi:10.1186/s12936-019-2905-9.
Stucke EM, et al. Serologic Responses to the PfEMP1 DBL-CIDR Head Structure May Be a Better Indicator of Malaria Exposure Than Those to the DBL-α Tag. Malar J. 2019 Aug 13;18(1):273. PubMed PMID: 31409360.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Serologic responses to the PfEMP1 DBL-CIDR head structure may be a better indicator of malaria exposure than those to the DBL-α tag. AU - Stucke,Emily M, AU - Niangaly,Amadou, AU - Berry,Andrea A, AU - Bailey,Jason A, AU - Coulibaly,Drissa, AU - Ouattara,Amed, AU - Lyke,Kirsten E, AU - Laurens,Matthew B, AU - Dara,Antoine, AU - Adams,Matthew, AU - Pablo,Jozelyn, AU - Jasinskas,Algis, AU - Nakajima,Rie, AU - Zhou,Albert E, AU - Agrawal,Sonia, AU - Friedman-Klabanoff,DeAnna J, AU - Takala-Harrison,Shannon, AU - Kouriba,Bourema, AU - Kone,Abdoulaye K, AU - Rowe,J Alexandra, AU - Doumbo,Ogobara K, AU - Felgner,Philip L, AU - Thera,Mahamadou A, AU - Plowe,Christopher V, AU - Travassos,Mark A, Y1 - 2019/08/13/ PY - 2019/03/11/received PY - 2019/08/05/accepted PY - 2019/8/15/entrez PY - 2019/8/15/pubmed PY - 2019/11/27/medline KW - Immunity KW - Malaria KW - Microarray KW - PfEMP1 KW - Plasmodium falciparum KW - Seroreactivity KW - var genes SP - 273 EP - 273 JF - Malaria journal JO - Malar. J. VL - 18 IS - 1 N2 - BACKGROUND: Plasmodium 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). METHODS: A 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. RESULTS: Malian 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. CONCLUSIONS: Larger 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. SN - 1475-2875 UR - https://www.unboundmedicine.com/medline/citation/31409360/Serologic_responses_to_the_PfEMP1_DBL-CIDR_head_structure_may_be_a_better_indicator_of_malaria_exposure_than_those_to_the_DBL-α_tag L2 - https://malariajournal.biomedcentral.com/articles/10.1186/s12936-019-2905-9 DB - PRIME DP - Unbound Medicine ER -