Poster Presentation Lorne Infection and Immunity 2023

Defining the mechanisms of action of antibodies against Plasmodium vivax malaria (#180)

Kaitlin Pekin 1 2 , Herbert Opi 1 3 4 , Liriye (Lydia) Kurtovic 1 3 , Gaoqian Feng 1 4 , Daisy Mantila 5 , Benishar Kombut 5 , Maria Ome-Kaius 5 , Chris King 6 , James Kazura 6 , Moses Laman 5 , Ivo Mueller 7 , Leanne Robinson 1 7 8 , James Beeson 1 2 3 4
  1. Burnet Institute, Melbourne, VIC, Australia
  2. Department of Microbiology, Monash University, Clayton, VIC, Australia
  3. Department of Immunology, Monash University, Clayton, VIC, Australia
  4. Department of Medicine, The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia
  5. Papua New Guinea Institute of Medical Research, Mandang, Papua New Guinea
  6. Case Western Reserve University, Cleveland, OH, USA
  7. Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia
  8. School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia

Effective vaccines against both Plasmodium falciparum and P. vivax will be essential to achieve malaria elimination goals globally. There have been great strides in developing P. falciparum vaccines but substantially less progress has been made for P. vivax. This is partly due to a lack of knowledge of key immune functions targeting P. vivax infection. Antibodies play an essential role in malaria immunity and can act by activating the complement system, mediating binding to Fcγ-receptors expressed by immune cells and promoting opsonic phagocytosis. However, currently we have limited knowledge on the functional activities of acquired antibodies to P. vivax.

In a cohort of children (n=37; ages 5-14), resident in a malaria-endemic region of PNG, we quantified functional antibody responses to four major P. vivax vaccine candidate antigens - AMA1, MSP3α and MSP1-19, and the two allelic forms of CSP. Specifically, we quantified IgG and cytophilic IgG subclasses, antibody-mediated complement fixation, Fcγ-receptor binding (types I, IIa and IIIa) and antibody-mediated opsonic phagocytosis of antigen-coated beads by THP-1 monocyte cells.

Children poorly acquired antibodies with complement-fixing activity to all antigens tested, whereas antibodies to MSP3α and AMA1 antigens mediated Fcγ receptor binding. Substantial opsonic phagocytosis activity with THP-1 cells was only observed with MSP3α coated beads. IgG1 and IgG3 were correlated with functional antibody responses. Limited functional activity observed with the other antigens in this cohort may be explained by the lower acquisition IgG cytophilic subclasses. Further studies will investigate these responses in other cohorts, the neutrophil-mediated phagocytosis and other antigen targets of functional antibodies.

Our findings suggest that antibodies to P. vivax antigens can mediate a range of effector functions, including opsonic phagocytosis, and acquired functional antibodies target some antigens more effectively. This contributes to our knowledge of P. vivax immunity and will be valuable for the development of effective vaccines.