Poster Presentation Lorne Infection and Immunity 2022

Assessment of IgG3 as a serological exposure marker for Plasmodium vivax malaria in moderate endemic areas  (#214)

Yanie Tayipto 1 2 , Jason Rosado 3 , Dionicia Gamboa 4 , Herbert Opi 5 , James Beeson 5 , Leanne Robinson 5 , Ivo Mueller 1 2 , Rhea Longley 1 2
  1. Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia
  2. Medical Biology, University of Melbourne, Melbourne, Victoria, Australia
  3. Unité Malaria: Parasites et Hôtes, Département Parasites et Insectes Vecteurs, Institut Pasteur, Paris, France
  4. Laboratorio ICEMR-Amazonia, Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, Peru
  5. Burnet Institute, Melbourne, Victoria, Australia

A more sensitive surveillance tool is needed to accelerate the elimination of Plasmodium vivax. P. vivax causes low parasitemia and is also found in other organs, apart from in blood circulation, which may not be detected using microscopy, PCR, or RDT. To address this challenge, our laboratory has developed an 8-antigen panel that can detect total IgGs as serological markers of P. vivax exposure within the prior 9 months in low endemic areas. In higher endemic areas, total IgG is more long-lived, resulting in poorer performance of this panel. In this study, we aimed to adapt our serological marker tool by applying a more short-lived antibody biomarker. Using a multiplex assay, we first measured antibody kinetics of total IgG, IgG1, IgG3, IgM and C1q-fixing antibodies against 29 P. vivax antigens over 36 weeks following asymptomatic P. vivax infection in PNG children (n=33). IgG3 and C1q-fixing antibodies declined faster to background level than total IgG, IgG1 and IgM. We then assessed IgG3 performance in classifying recent exposure in a cohort of Peruvian individuals (n=590). IgG3 had sensitivity and specificity of 70%, while total IgG was a better marker, with sensitivity and specificity of 80%. We further explored factors that impact the acquisition and decay of IgG3 in this cohort. IgG3 was associated with age, living in a higher endemic area, and having three or more blood stage P. vivax infections within the last 13 months. This result showed that higher exposure is required to attain IgG3 against the 29 P. vivax proteins used, so further study is still needed before implementing IgG3 for a serological marker tool.

  1. Longley RJ, White MT, Takashima E, Brewster J, Morita M, Harbers M, Obadia T, Robinson LJ, Matsuura F, Liu ZSJ et al. (2020) Development and validation of serological markers for detecting recent Plasmodium vivax infection. Nat Med. 26(5):741-749.
  2. Rosado J, White MT, Longley RJ, Lacerda M, Monteiro W, Brewster J, Sattabongkot J, Guzman-Guzman M, Llanos-Cuentas A, Vinetz JM et al. (2021) Heterogeneity in response to serological exposure markers of recent Plasmodium vivax infections in contrasting epidemiological contexts. PLOS Neglected Tropical Diseases. 15(2):e0009165.