E-Poster with pre-recorded video presentation Lorne Infection and Immunity 2021

Complement and Fcγ-receptor mediated antibody effector functions target merozoites and are associated with protection from severe malaria in children (#233)

Sandra Chishimba 1 2 , Jo-Anne Chan 1 2 3 , Linda Reiling 1 , Julia Cutts 1 4 , Gaoqian Feng 1 4 , Laurens Manning 5 6 , Ivo Mueller 7 , Moses Laman 6 , Timothy Davis 5 , Paul R Gilson 1 , Bruce D Wines 1 8 9 , Mark P Hogarth 1 8 9 , Stephen Rogerson 4 , James Beeson 1 2 3
  1. Life Sciences, Burnet Institute, Melbourne, Victoria, Australia
  2. Medicine at Royal Melbourne Hospital, University of Melbourne, Melbourne, Victoria, Australia
  3. Immunology and Microbiology, Central Clinical School, Monash University, Melbourne, Victoria, Australia
  4. Medicine at Royal Melbourne Hospital, Peter Doherty Institute, University of Melbourne, Melbourne, Victoria, Australia
  5. Internal Medicine, The University of Western Australia, Perth, Western Australia, Australia
  6. Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea
  7. Population Health and Immunity, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia
  8. Central Clinical School, Monash University, Melbourne, Victoria
  9. Pathology, University of Melbourne, Melbourne, Victoria, Australia

Clearance of malaria parasites in the blood may involve complement proteins that can lead to merozoite lysis and inhibition of RBC invasion and replication. Opsonization of malaria blood-stages by antibodies and complement, which interact with complement receptors (CR) and Fcγ-receptors, can promote phagocytic clearance by monocytes and neutrophils.  However, complement dysfunction and excessive activation of immune cells can also potentially contribute to pathogenesis of severe disease. Currently, there are limited data on complement and Fc-gamma receptor (FcγR) mediated responses in severe malaria. In this study we investigated, for the first time, antibodies that fix and activate complement or interact with different Fcγ-receptors to promote phagocytosis in a case-control study of severe malaria in 383 young children in Papua New Guinea (PNG). Our results show that IgG and complement (C1q) fixing antibodies were significantly lower in children with severe malaria compared to children with mild uncomplicated malaria (p=0.04 and p=0.02 respectively). IgG strongly correlated with functional antibodies in both severe and uncomplicated malaria. Further, children with broad antibody multi-functional activity had a significantly reduced odds of severe disease. Our results show differences in response types between severe and uncomplicated disease among children that provide new insights into mechanisms that could be exploited in vaccine development to provide protection against severe disease.