BACKGROUND: Vaccine efforts have been hampered due the parasites antigenic complexity and uncertainty as to what kind of immune response would be most effective at protecting individuals from disease. Placental malaria is the syndrome where it is clear which one of the roughly 60 PfEMP1 (in this case VAR2CSA) is responsible for disease, making VAR2CSA an ideal antigen to examine immune responses and protection. Neutrophil Antibody dependent respiratory burst (ADRB) has been identified as important for protection towards merozoite antigens but little work has been done towards infected erythrocytes (IE), also previous assays used high numbers of neutrophils, making them impractical. AIM: Examine whether neutrophil ADRB is associated with protection using a new high throughput assay. METHODS: We did a case control study with a cohort of 127 women, grouped into non-infected, infected with placental malaria, infected but no-placental malaria based on placental histology, peripheral blood smear and PCR results at delivery and measured ADRB at 14-26 gestation weeks (gw). For the ADRB assay CS2 IE (which express VAR2CSA) were opsonised in a 384 well plate with plasma. Neutrophils isolated from whole blood were added (2x104/well) in a buffer containing luminol, Horse radish peroxidase (catalyst) and IL-8 (primer). Luminescence was measured using a plate reader. Plasma was positive for inducing ROS if luminescence was 2SD above that seen in Melbourne controls. RESULTS: The percentage of women whose plasma at 14-26gw induced ADRB was higher in the group who were infected at delivery but did not have placental malaria (74% positive for ADRB), compared to those women who did have placental malaria at delivery (42% positive for ADRB)(P=0.014, Chi2). CONCLUSION: This is the first data which suggests that antibody towards VAR2CSA-IE induce ADRB which protects against placental malaria and that ADRB may be an important mechanism of immunity to the IE.