Poster Presentation Lorne Infection and Immunity 2014

The role of binding inhibitory antibodies for Plasmodium falciparum erythrocyte binding antigen (EBA175) in protecting children from symptomatic malaria (#160)

Vashti Irani 1 2 3 , Paul Ramsland 1 2 , Rosemary Ffrench 1 2 , Ivo Mueller 4 5 , Peter Siba 6 , James Beeson 1 3 , Jack S Richards 1 3
  1. Burnet Intitute, Melbourne, VIC, Australia
  2. Department of Immunology, Monash University, Melbourne, VIC, Australia
  3. Department of Medicine , Melbourne University, Melbourne, VIC, Australia
  4. Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia
  5. Barcelona Centre for International Health Research, Barcelona, Spain
  6. Papua New Guinea Institute of Medical Research, Madang, PNG

The blood stage of the malaria life cycle is associated with symptomatic disease. Importantly, individuals living in malaria endemic areas develop natural immunity that protects them from symptomatic disease. Immunity develops with time and cumulative parasite exposure, and the antibody response against blood stage parasites plays a major role. Some of these antibodies are known to target antigens on the invasive form of the parasite, the merozoite, and these antibodies are able to inhibit erythrocyte invasion. Multiple merozoite antigens are targeted, including Plasmodium falciparum vaccine candidate, EBA175. The presence of high levels of antibodies to EBA175 is associated with clinical protection, and it is believed that these antibodies function by inhibiting the binding of EBA175 to its erythrocyte receptor, glycophorin A.

To further understand the immunological mechanisms that mediate immunity, there is a requirement for a broader array of functional assays, especially for use in clinical studies. To address this, we developed immunoassays to specifically detect antibodies that inhibit the EBA175: glycophorin A interaction. These assays were tested in a cohort of 206 Papua New Guinean children who were treated at enrolment to clear parasitaemia, and prospectively observed for six months to detect reinfection and clinical disease. Approximately half the children were able to inhibit the binding of EBA175 to glycophorin A. The presence of binding inhibitory antibodies correlated with the presence of IgG levels to EBA175-Region II by ELISA, suggesting that high antibody levels were required to mediate this functional effect. It appeared that these antibodies developed with cumulative exposure, while concurrent infection with parasites boosted the response. Importantly, binding inhibitory antibodies were associated with protection from symptomatic disease. This study provides insight into the development of functional antibodies to EBA175, and helps understand the functional role of binding inhibitory antibodies in naturally acquired and vaccine induced immunity.