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

Keep holding on: the role of antibody avidity in immunity to malaria (#304)

Jessica L Horton 1 2 , Jo-Anne Chan 1 2 3 , Liriye Kurtovic 1 , Linda Reiling 1 , Gaoqian Feng 1 , Kristina Persson 4 , James W Kazura 5 , Arlene Dent 5 , Itziar Ubillos 6 , Jahit Sacarlal 7 8 , John J Aponte 6 8 , Carlota Dobano 6 8 , Robin F Anders 9 , James S McCarthy 10 11 , Michelle J Boyle 11 , James G Beeson 1 2 3
  1. Burnet Institute, Melbourne, VIC, Australia
  2. Department of Medicine, University of Melbourne, Melbourne, VIC, Australia
  3. Department of Immunology, Central Clinical School, Monash University, Melbourne, VIC, Australia
  4. Division of Clinical Chemistry and Pharmacology, Lund University, Lund, Sweden
  5. Center for Global Health and Diseases, Case Western Reserve University, Cleveland, Ohio, USA
  6. ISGlobal, Hospital Clínic Universitat de Barcelona, Barcelona, Catalonia, Spain
  7. Faculdade de Medicina, Universidade Eduardo Mondlane (UEM), Maputo, Mozambique
  8. Centro de Investigação em Saúde de Manhiça, Maputo, Mozambique
  9. Department of Biochemistry and Genetics, La Trobe University, Melbourne, VIC
  10. Doherty Institute, Melbourne, VIC, Australia
  11. QIMR-Berghofer Medical Research Institute, Herston, QLD

A major hurdle in the development of a highly efficacious and long-lasting malaria vaccine is the absence of clear correlates of protective immunity. Antibodies are critical to mediate immunity to malaria but concentration alone is not sufficient to guarantee clinical protection. Therefore, antibody properties and functional activity must be more closely investigated to identify highly protective antibodies. Antibody binding strength, or avidity, is frequently described as the quality of an antibody response and has proven a valuable marker of infection and immunity in other diseases. However, although avidity in malaria is often associated with pathogen exposure, previous studies have demonstrated an inconsistent association with protection from parasitemia or clinical disease. Elucidating the role of high avidity interactions in the immune response to malaria will identify beneficial antibody properties which should be targeted in future vaccine development. In this work, IgG avidity against key vaccine targets was assessed in separate malaria vaccine clinical trials, comprising malaria-naïve and naturally-exposed individuals, and considered in relation to antibody maintenance and functional mechanisms. In a Phase II trial of the leading malaria vaccine candidate, RTS,S, high avidity binding did not improve recruitment of complement proteins or Fcγ-receptor binding but was associated with improved maintenance of IgG over time. This effect was also observed when investigating the antibody response to the major B cell epitope of the RTS,S target protein. The association between high avidity and IgG longevity, but not function, was supported in a cohort of Australian adults enrolled in a Phase I trial of an alternative vaccine candidate. We further investigated the presence of high avidity, well-maintained antibody populations in vaccine-induced responses in mice. Defined markers of long-term immunity are crucial for the design and testing of improved malaria vaccines. To eliminate this global health burden, the development of a vaccine capable of inducing sustained protection is essential.