Neutralizing Antibodies against Plasmodium falciparum Associated with Successful Cure after Drug Therapy

Abstract

An effective antibody response can assist drug treatment to contribute to better parasite clearance in malaria patients. To examine this, sera were obtained from two groups of adult patients with acute falciparum malaria, prior to drug treatment: patients who (1) have subsequent recrudescent infection, or (2) were cured by Day 28 following treatment. Using a Plasmodium falciparum antigen library, we examined the antibody specificities in these sera. While the antibody repertoire of both sera groups was extremely broad and varied, there was a differential antibody profile between the two groups of sera. The proportion of cured patients with antibodies against EXP1, MSP3, GLURP, RAMA, SEA and EBA181 was higher than the proportion of patients with recrudescent infection. The presence of these antibodies was associated with higher odds of treatment cure. Sera containing all six antibodies impaired the invasion of P. falciparum clinical isolates into erythrocytes. These results suggest that antibodies specific against EXP1, MSP3, GLURP, RAMA, SEA and EBA181 in P. falciparum infections could assist anti-malarial drug treatment and contribute to the resolution of the malarial infection.

Fig 1. Antibody-mediated inhibition of Pf RBC invasion.

RBC invasion inhibition efficiency, mediated by the human patients sera, was defined as the ratio of the subtraction of parasitemia in the test well (test patients sera) from the parasitemia in the control well (normal human serum) to the parasitemia in the control well, expressed as a percentage. 6Ab +ve refers to sera (both cured and recrudescent sera) containing specific antibodies against all six antigens (n = 14); Cured 5Ab +ve refers to cured sera containing specific antibodies against the five antigens (n = 14); 6Ab–ve refers to sera (both cured and recrudescent sera) with absence of specific antibodies against the six antigens (n = 6); Recrudescent 5Ab +ve refers to recrudescent sera containing specific antibodies against the five antigens (n = 7). Pooled cured refers to sera pooled from all cured patients (n = 40) and pooled recrudescent refers to sera pooled from all recrudescent patients (n = 28). Each point in graph represents one P. falciparum isolate (n = 12). Horizontal line in graph represents mean inhibition efficiency between the 12 P. falciparum isolates. * denotes p <0.05; ** denotes p <0.01; *** denotes p <0.001; **** denotes p <0.0001, by Mann-Whitney U-test (adjusted for multiple comparison using Bonferroni correction).