Abstract:
Young infants are less susceptible to severe episodes of malaria but the targets
and mechanisms of protection are not clear. Cord blood antibodies may play an
important role in mediating protection but many studies have examined their
association with the outcome of infection or non-severe malaria. Here, we
investigated whether cord blood IgG to Plasmodium falciparum merozoite
antigens and antibody-mediated effector functions were associated with reduced
odds of developing severe malaria at different time points during the first year of
life. We conducted a case-control study of well-defined severe falciparum malaria
nested within a longitudinal birth cohort of Kenyan children. We measured cord
blood total IgG levels against five recombinant merozoite antigens and antibody
function in the growth inhibition activity and neutrophil antibody-dependent
respiratory burst assays. We also assessed the decay of maternal antibodies
during the first 6months of life. The mean antibody half-life range was
2.51months (95% confidence interval (CI): 2.19-2.92) to 4.91months (95% CI:
4.47-6.07). The rate of decline of maternal antibodies was inversely proportional
to the starting concentration. The functional assay of antibody-dependent
respiratory burst activity predicted significantly reduced odds of developing
severe malaria during the first 6months of life (Odds ratio (OR) 0.07, 95% CI:
0.007-0.74, P=0.007). Identification of the targets of antibodies mediating
antibody-dependent respiratory burst activity could contribute to the
development of malaria vaccines that protect against severe episodes of malaria
in early infancy.