Maternally derived antibodies to Schizont Egress Antigen-1 and protection of infants from severe malaria.

25 Aug 2018
Kurtis JD, Raj DK, Michelow IC, Park S, Nixon CE, McDonald EA, Nixon CP, Pond-Tor S, Jha A, Taliano RJ, Kabyemela ER, Friedman JF, Duffy PE, Fried M

Background

In holoendemic areas, children suffer the most from Plasmodium falciparum malaria, yet newborns and young infants express a relative resistance to both infection and severe malarial disease (SM). This relative resistance has been ascribed to maternally derived anti-parasite IgG, however, the targets of these protective antibodies remain elusive.

Methods

We enrolled N=647 newborns at birth who resided in a malaria holoendemic region of Tanzania. We collected cord blood, measured antibodies to PfSEA-1, and related these antibody levels to risk of severe malaria in the first twelve months of life. In addition, we vaccinated female mice with PbSEA-1, mated them, and challenged their pups with P. berghei ANKA parasites to assess the impact of maternal PbSEA-1 vaccination on newborn resistance to malaria.

Results

Children with high cord blood anti-PfSEA-1 antibody levels had 51.4% fewer cases of SM compared to individuals with lower anti-PfSEA-1 levels over 12 months of follow-up (P = 0.03). In three trials, pups born to PbSEA-1 vaccinated dams had significantly lower parasitemia and significantly longer survival times following P. berghei challenge compared to pups born to control dams.

Conclusions

We demonstrate that maternally derived, cord-blood anti-PfSEA-1 antibodies predict significantly decreased risk of SM in infants and vaccination of mice with PbSEA-1 prior to pregnancy protects their offspring from lethal P. berghei parasite challenge. These results identify, for the first time, a parasite specific target of maternal antibodies that protect infants from SM and suggest that vaccination of pregnant women with PfSEA-1 may afford a survival advantage to their offspring.