TY - JOUR
T1 - Global genetic diversity of var2csa in Plasmodium falciparum with implications for malaria in pregnancy and vaccine development
AU - Benavente, Ernest Diez
AU - Oresegun, Damilola R
AU - de Sessions, Paola Florez
AU - Walker, Eloise M
AU - Roper, Cally
AU - Dombrowski, Jamille G
AU - de Souza, Rodrigo M
AU - Marinho, Claudio R F
AU - Sutherland, Colin J
AU - Hibberd, Martin L
AU - Mohareb, Fady
AU - Baker, David A
AU - Clark, Taane G
AU - Campino, Susana
N1 - Publisher Copyright:
© 2018, The Author(s).
PY - 2018/10/18
Y1 - 2018/10/18
N2 - 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.
AB - 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.
KW - Antibodies, Protozoan
KW - Antigenic Variation/genetics
KW - Antigens, Protozoan/genetics
KW - Female
KW - Genetic Variation
KW - Haplotypes
KW - Humans
KW - Malaria Vaccines/immunology
KW - Malaria, Falciparum/genetics
KW - Placenta/parasitology
KW - Plasmodium falciparum/immunology
KW - Pregnancy
KW - Pregnancy Complications, Parasitic/immunology
U2 - 10.1038/s41598-018-33767-3
DO - 10.1038/s41598-018-33767-3
M3 - Article
C2 - 30337594
SN - 2045-2322
VL - 8
SP - 15429
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 15429
ER -