Liu, Zoe Shih JungSattabongkot, JetsumonWhite, MichaelChotirat, SadudeeKumpitak, ChalermponTakashima, EizoHarbers, MatthiasTham, Wai HongHealer, JulieChitnis, Chetan E.Tsuboi, TakafumiMueller, IvoLongley, Rhea J.2025-05-312025-05-31PubMed:35260169http://www.scopus.com/inward/record.url?scp=85126077599&partnerID=8YFLogxKhttps://hdl.handle.net/1885/733756205Background: Plasmodium vivax (P. vivax) is the dominant Plasmodium spp. causing the disease malaria in low-transmission regions outside of Africa. These regions often feature high proportions of asymptomatic patients with sub-microscopic parasitaemia and relapses. Naturally acquired antibody responses are induced after Plasmodium infection, providing partial protection against high parasitaemia and clinical episodes. However, previous work has failed to address the presence and maintenance of such antibody responses to P. vivax particularly in low-transmission regions. Methods: We followed 34 patients in western Thailand after symptomatic P. vivax infections to monitor antibody kinetics over 9 months, during which no recurrent infections occurred. We assessed total IgG, IgG subclass and IgM levels to up to 52 P. vivax proteins every 2–4 weeks using a multiplexed Luminex® assay and identified protein-specific variation in antibody longevity. Mathematical modelling was used to generate the estimated half-life of antibodies, long-, and short-lived antibody-secreting cells. Results: Generally, an increase in antibody level was observed within 1-week post symptomatic infection, followed by an exponential decay of different rates. We observed mostly IgG1 dominance and IgG3 sub-dominance in this population. IgM responses followed similar kinetic patterns to IgG, with some proteins unexpectedly inducing long-lived IgM responses. We also monitored antibody responses against 27 IgG-immunogenic antigens in 30 asymptomatic individuals from a similar region. Our results demonstrate that most antigens induced robust and long-lived total IgG responses following asymptomatic infections in the absence of (detected) boosting infections. Conclusions: Our work provides new insights into the development and maintenance of naturally acquired immunity to P. vivax and will guide the potential use of serology to indicate immune status and/or identify populations at risk.We gratefully acknowledge the extensive field teams that contributed to sample collection and qPCR assays in the original cohort studies. We thank all of the individuals who participated in each of the studies and the Australian and Thai Red Cross for donation of blood samples. We thank the Volunteer Blood Donor Registry at WEHI for donation of plasma samples and Lina Laskos for their collection and advice. We thank Christopher King (Case Western Reserve University) for provision of the PNG control plasma pool. We thank Fumie Matsuura (CellFree Sciences), Christele Huon (Institut Pasteur) and Jakub Gruszczyk (WEHI) for contributing to expression of proteins. We thank Connie Li-Wai-Suen for writing the R script used for converting MFI values to relative antibody units. Funding was provided by the National Health and Medical Research Council (#1092789, #1134989, and #1043345 to IM, #1143187 to W-HT, and #1173210 to RL), the Global Health Innovative Technology Fund ( https://www.ghitfund.org/ ) (T2015-142 to IM) and the National Institute of Allergy and Infectious Diseases (NIH grant 5R01 AI 104822 to JS). We acknowledge support from the National Research Council of Thailand and the Victorian State Government Operational Infrastructure Support and Australian Government NHMRC IRIISS. W-HT was a Howard Hughes Medical Institute-Wellcome Trust International Research Scholar ( https://www.hhmi.org/programs/biomedical-research/international-programs,~208693/Z/17/Z ). ZS-JL was supported by the Melbourne Research Scholarship, University of Melbourne.17enPublisher Copyright: © 2022, The Author(s).202210.1186/s12916-022-02281-985126077599