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

Sci Rep. 2018 Oct 18;8(1):15429. doi: 10.1038/s41598-018-33767-3.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • Antibodies, Protozoan
  • Antigens, Protozoan
  • Malaria Vaccines
  • VAR2CSA protein, Plasmodium falciparum