Poster Presentation Lorne Infection and Immunity 2023

Temporal kinetics of functional antibody responses following naturally acquired Plasmodium vivax malaria infections (#159)

Rhea Longley 1 , Herbert Opi 2 , Kael Schoffer 1 , Yanie Tayipto 1 , Jessica Brewster 1 , Kaitlin Pekin 2 , Macie Lamont 1 , Benson Kiniboro 3 , Leanne Robinson 2 , Jetsumon Sattabongkot Prachumsri 4 , James Beeson 2 , Ivo Mueller 1
  1. Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia
  2. Burnet Institute, Melbourne, VIC, Australia
  3. Papua New Guinea Institute of Medical Research, Madang, PNG
  4. Mahidol Vivax Research Unit, Mahidol University, Bangkok

Malaria infections due to Plasmodium vivax are a major challenge for elimination in the Asia-Pacific region. Despite progress in vaccine development for Plasmodium falciparum, there remains no advanced P. vivax vaccine candidates. Improving our knowledge of the targets and functional mechanisms of naturally acquired immunity to P. vivax could assist development of better P. vivax-specific vaccines. Antibodies play an important role in acquired immunity and can act in various ways including direct inhibition, activation of complement, and engagement with Fcγ-receptors (FcR). The major objective of this study was to characterise the acquisition and longevity of functional antibody responses following P. vivax infection.

 

We developed a multiplexed assay to measure functional antibody responses (complement fixing, FcR binding) against a panel of 30 P. vivax proteins simultaneously. We observed that both complement-fixing and FcR-binding responses were highest against the blood-stage antigens AMA1, RBP2b, MSP1-19, RAMA and MSP8. P. vivax-specific complement-fixing responses were higher in individuals with at least 2 P. vivax infections in the prior year in a Thai observational cohort (n=775) from a low-transmission setting and were weakly-moderately associated with age. Utilising a 9-month follow-up study following clinical P. vivax infections in Thailand (n=36), we observed that complement-fixing and FcR-binding responses were shorter lived than total IgG responses, declining significantly to background by 2-4 months post-infection. Temporal longevity of P. vivax­-specific complement-fixing antibodies was remarkably similar in PNG children (n=33) following asymptomatic P. vivax infections.

 

These results demonstrate that P. vivax-specific functional antibody responses elicited following P. vivax infections are short-lived and suggests a focus of vaccine research should be inducing long-lived functional antibody responses. Future studies will assess downstream Fc-mediated effector functions such as phagocytosis and relate these to the FcR-binding antibodies measured.