9PI8

EV-D68 in complex with G12 Fc

Summary for 9PI8

• Entry DOI: 10.2210/pdb9pi8/pdb
• EMDB information: 71655
• Descriptor: viral protein 1, viral protein 2, viral protein 3, ... (5 entities in total)
• Functional Keywords: ev-d68, g12, antibody, structural genomics, center for structural biology of infectious diseases, csbid, virus, virus-immune system complex, virus/immune system
• Biological source: Vicugna pacos; More
• Total number of polymer chains: 5
• Total formula weight: 136763.24

Authors

Klose, T.,Kuhn, R.J.,Center for Structural Biology of Infectious Diseases (CSBID) (deposition date: 2025-07-10, release date: 2026-06-17)

Primary citation

Hodge, E.A.,Archer, J.,Anderson, J.S.,Warner, N.L.,Tremblay, J.,Klose, T.,Park, S.,Hinkley, T.,Khandhar, A.P.,Kuhn, R.,Shoemaker, C.B.,Erasmus, J.H.
An RNA-to-RNA pipeline for rapid antiviral antibody development.
Mol.Ther., 2026

PubMed Abstract: Rapid development of antibody therapeutics is often hindered by dependencies on recombinant protein production, both for antigen generation and for antibody manufacturing. To overcome these bottlenecks, we established a self-amplifying replicon RNA (repRNA) immunization and therapeutic delivery platform that enables an end-to-end RNA-to-antibody-to-RNA workflow. In this approach, alpacas are immunized with repRNA encoding virus-like particles to elicit antibody responses, peripheral blood mononuclear cells are harvested to construct phage display libraries, and broadly neutralizing heavy-chain-only antibodies (VHHs [variable heavy domain of the heavy chain]) are identified through high-throughput screening. Lead VHHs are then re-encoded into repRNA for in vivo delivery as therapeutic constructs, with engineering options for valency, potency, and serum half-life. As proof of concept, we applied this platform against enterovirus D68 (EV-D68), an emerging pathogen associated with severe respiratory disease and acute flaccid myelitis in children for which no vaccines or treatments exist. repRNA-encoded VHHs protected mice from EV-D68 challenge in both lungs and nasal cavities, and cryoelectron microscopy revealed the capsid-binding footprint and mechanism of neutralization. Together, these findings demonstrate a modular platform for rapid discovery and delivery of antiviral biologics, with EV-D68 serving as a prototype application.

PubMed: 41964219
DOI: 10.1016/j.ymthe.2026.04.021

Experimental method

ELECTRON MICROSCOPY (2.11 Å)