The RVNA Protocol: A Systems Architecture for Post-Exposure Clearance of Rabies Virus in the Central Nervous System

The RVNA (Rabies Virtual Neutralising Active) Protocol is a systems-engineered, multi-modal translational architecture for active clearance of rabies virus from the central nervous system (CNS) in patients with established encephalomyelitis — a condition that remains uniformly fatal under all current standards of care. The protocol integrates four validated components: 1. Convection-Enhanced Delivery (CED) for direct parenchymal antibody infusion, bypassing the blood-brain barrier (Parvar et al., 2025);2. Targeted regional brain hypothermia (32–33 °C) to slow viral transport, preserve ATP, and reduce excitotoxicity while maintaining systemic normothermia and peripheral immunity (Jackson, 2011; Bolibok, 2026);3. Dual-antibody delivery combining full-length IgG monoclonal antibodies (SYN023) for bulk extracellular neutralization with synaptic-penetrating nanobodies (VHH) engineered to access the narrow (~20–30 nm) synaptic cleft (Liu et al., 2025; Terryn et al., 2016);4. Pediatric neuroplasticity exploitation leveraging developmental synaptic remodeling and BDNF epigenetic modulation to maximize functional recovery post-clearance (James et al., 2026; Heinsberg et al., 2025; Yan et al., 2025). The protocol is structured into six actionable clinical phases: diagnosis & triage, catheter placement, hypothermia induction, dual-antibody infusion, monitoring & support, and neurorehabilitation. This document is a theoretical systems engineering proposal intended for compassionate-use evaluation, translational research, and peer review. It has not been clinically validated and does not constitute medical advice.