Folia Parasitologica 72:019 (2025) | DOI: 10.14411/fp.2025.019

Marginal cytokine modulation by Schistosoma mansoni soluble egg antigen in SARS-CoV-2-infected K18-hACE2 mice

Yi Mu^{1, 9}, Kexin Yan ORCID...^{2, 9}, Donald P. McManus ORCID...^{1, 10}, Wilson Nguyen ORCID...², Daniel J. Rawle ORCID...², Jason A. Roberts ORCID...^{3, 4, 5, 6}, Malcolm K. Jones ORCID...^{1, 7}, Pengfei Cai ORCID...^{1, 8}

¹ Molecular Parasitology Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, Australia;

² Inflammation Biology, QIMR Berghofer Medical Research Institute, Brisbane, Australia;

³ University of Queensland Centre for Clinical Research, Faculty of Medicine, University of Queensland, Brisbane, Australia;

⁴ Herston Infectious Diseases Institute (HeIDI), Metro North Health, Brisbane, Australia;

⁵ Departments of Pharmacy and Intensive Care Medicine, Royal Brisbane and Women's Hospital, Brisbane, Australia;

⁶ Division of Anaesthesiology Critical Care Emergency and Pain Medicine, Nîmes University Hospital, University of Montpellier, Nîmes France

⁷ School of Veterinary Science, University of Queensland, Brisbane, Australia;

⁸ School of Biomedical Sciences, University of Queensland, Brisbane, Australia;

⁹ These authors contributed equally to this work.

¹⁰ Deceased

Herein, we explore the potential influence of Schistosoma mansoni Sambon, 1907 soluble egg antigen (SmSEA) on the immunopathology of COVID-19 in K18-hACE2 mice infected with an Omicron BA.5 isolate of SARS-CoV-2. SmSEA treatment was delivered in a single dose by intraperitoneal injection, shortly after intrapulmonary inoculation of SARS-CoV-2. RNA-seq identified 36 differentially expressed genes in the spleens of virus-infected mice treated with SmSEA vs. PBS on day 5 post infection. Ingenuity Pathway Analysis of these genes suggested marginal modulation of cytokine responses, with upregulation of the IL-10 and IL-4 signatures and downregulation of the IFNγ signature. However, cytokine responses and histopathology in the lungs were largely unaffected. Future work will require purification of active helminth compounds and dosing and scheduling optimisation.

Keywords: COVID-19; severe acute respiratory syndrome coronavirus 2; schistosome; helminth-derived antigens; therapeutic immunomodulators; helminth therapy

Received: February 3, 2025; Revised: March 15, 2025; Accepted: April 10, 2025; Published online: June 16, 2025  Show citation