Heritable transgenic schistosomes as a living platform for SARS-CoV-2 neutralizing antibody secretion
- Wannaporn Ittiprasert
- Michael J. Smout
- Victoria H. Mann
- Matthew Moyle
- Sean M. Kinahan
- Daniel N. Ackerman
- Danielle N. Rivera
- Joshua L. Santarpia
- Eric C. Carnes
- Margaret M. Mentink-Kane
- Marina Reis Costa
- Cornelis H. Hokke
- Meta Roestenberg
- Maria Elena Bottazzi
- Bethany K. Bracken
- Bruce A. Rosa
- Sergej Djuranovic
- Darren A. Pickering
- Paul R. Giacomin
- Daniel Watterson
- Naphak Modhiran
- Max F. Moescheid
- Christoph G. Grevelding
- Makedonka Mitreva
- Alex Loukas
- Paul J. Brindley
2026-08-26
We report the generation and propagation of not only the first heritable transgenic schistosome line but also a line that secretes a functional therapeutic protein in vivo. Using multiplexed CRISPR/Cas-mediated homology-directed knock-in targeted to a predicted genomic safe-harbor, we inserted a VHH–IgG1 Fc (termed C5-Fc) transgene into Schistosoma mansoni eggs. Single-miracidium infections of Biomphalaria glabrata yielded parental P0 lines; serial passage through snail and mouse hosts produced an F2 cohort in which all parasites carried the C5-Fc transgene and secreted C5-Fc into the murine venous circulation. Molecular assays confirmed chromosomal insertion, germline transmission and systemic secretion. Sera from mice harboring C5-Fc transgenic worms neutralized SARS-CoV-2 in vitro with potent activity consistent with the expected ACE2-binding blockade by the C5 variable domain of heavy-chain-only antibody (VHH). These results demonstrate (i) stable, heritable transgenesis of a platyhelminth, (ii) delivery of a biologically active antibody fragment by a live helminth in a mammalian host, and (iii) feasibility of using transgenic schistosomes as sustained, single-dose protein delivery platforms. This technology and delivery system enable new experimental approaches for schistosome biology and motivate exploration of living-foundry therapeutics.