Science Bite (3 min Oral Presentation) Lorne Infection and Immunity 2019

The impact of age on complement-fixing antibodies targeting P. vivax MSP3a (#76)

Damian Oyong 1 2 , Danny Wilson 3 4 , Bridget Barber 1 5 , Timothy Lawrence 5 6 , James Beeson 3 7 8 , Freya Fowkes 3 9 10 , Matthew Grigg 1 5 , Nick Anstey 1 , Michelle Boyle 3 11
  1. Menzies School of Health Research, Tiwi, NT, Australia
  2. Charles Darwin University, Darwin, NT, Australia
  3. Burnet Institute, Melbourne, Victoria, Australia
  4. Research Centre for Infectious Diseases, University of Adelaide, Adelaide, SA, Australia
  5. Infectious Diseases Society, Sabah-Menzies School of Health Research Clinical Research Unit, Queen Elizabeth Hospital, Kota Kinabalu, Sabah, Malaysia
  6. Jesselton Medical Centre, Kota Kinabalu, Sabah, Malaysia
  7. Department of Medicine, University of Melbourne, Melbourne, VIC, Australia
  8. Department of Microbiology and Central Clinical School, Monash University, Melbourne, VIC, Australia
  9. Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, VIC, Australia
  10. Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC, Australia
  11. QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia

Background

Complement-fixing antibodies targeting merozoite invasion of RBCs have been shown to mediate protective immunity against P. falciparum malaria. However, complement-fixing antibodies targeting P. vivax are uncharacterised, and whether protein structure or host age influence induction of the functional antibodies are unknown. We quantified the levels of complement-fixing antibodies targeting Merozoite Surface Proteins-3α (PvMSP3α) in children and adults with P. vivax malaria.

Methods

Plasma samples from 48 individuals (24 children and 28 adults) with P. vivax malaria were collected from a cohort study in Sabah, Malaysia during acute infection and 7 and 28 days following treatment. C1q fixing antibodies and IgM and IgG antibody subclasses targeting different regions of PvMSP3α regions (C-terminal, Block region, N-terminal) were measured by ELISA.

Results

Overall seroprevalence of C1q fixing antibodies was highest against PvMSP3α Block region (77.6%), followed by C-terminal (49.0%) and N-terminal (18.4%). IgG1, IgG3, and IgM were all significantly correlated with C1q-fixing antibodies and both purified IgG and IgM were capable of mediating C1q fixation to PvMSP3α. Levels of complement-fixing antibodies were similar between age groups, but IgM appeared to be more important in mediating complement fixation in children, compared to IgG3 in adults. Functional antibodies against PvMSP3α increased following acute infection 7 days after treatment, however rapidly waned to baseline at Day 28.

Conclusion

Complement-fixing antibodies are induced during acute P. vivax infection. PvMSP3α is a target of complement fixing antibodies and its immunogenicity was dependent on specific protein region. There were significant differences between induction of IgG1, IgG3, IgM and functional antibodies between children and adults. Our study demonstrates PvMSP3α antibodies mediate C1q fixation in people with P. vivax and shows the important influence of age in shaping specific antibody responses to P. vivax merozoite antigens. Further studies are warranted to understand the role of functional antibodies in protective immunity.