Global genetic diversity of var2csa in Plasmodium falciparum with implications for malaria in pregnancy and vaccine development

Ernest Diez Benavente, Damilola R Oresegun, Paola Florez de Sessions, Eloise M Walker, Cally Roper, Jamille G Dombrowski, Rodrigo M de Souza, Claudio R F Marinho, Colin J Sutherland, Martin L Hibberd, Fady Mohareb, David A Baker, Taane G Clark, Susana Campino

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Malaria infection during pregnancy, caused by the sequestering of Plasmodium falciparum parasites in the placenta, leads to high infant mortality and maternal morbidity. The parasite-placenta adherence mechanism is mediated by the VAR2CSA protein, a target for natural occurring immunity. Currently, vaccine development is based on its ID1-DBL2Xb domain however little is known about the global genetic diversity of the encoding var2csa gene, which could influence vaccine efficacy. In a comprehensive analysis of the var2csa gene in >2,000 P. falciparum field isolates across 23 countries, we found that var2csa is duplicated in high prevalence (>25%), African and Oceanian populations harbour a much higher diversity than other regions, and that insertions/deletions are abundant leading to an underestimation of the diversity of the locus. Further, ID1-DBL2Xb haplotypes associated with adverse birth outcomes are present globally, and African-specific haplotypes exist, which should be incorporated into vaccine design.

Original languageEnglish
Article number15429
Pages (from-to)15429
JournalScientific Reports
Volume8
Issue number1
DOIs
Publication statusPublished - 18 Oct 2018
Externally publishedYes

Keywords

  • Antibodies, Protozoan
  • Antigenic Variation/genetics
  • Antigens, Protozoan/genetics
  • Female
  • Genetic Variation
  • Haplotypes
  • Humans
  • Malaria Vaccines/immunology
  • Malaria, Falciparum/genetics
  • Placenta/parasitology
  • Plasmodium falciparum/immunology
  • Pregnancy
  • Pregnancy Complications, Parasitic/immunology

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