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

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

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.

Journal: Scientific reports
DOI: 10.1038/s41598-018-33767-3
Year: 2018

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