This article, authored by Dr. Kabanga Tshibanga MD; MPH under the authority of Omega Foundry, presents OMEGA-GENESIS, a revolutionary vaccine architecture designed for the global eradication of Mycobacterium tuberculosis (Mtb). Moving beyond traditional, static immunization logic, the paper introduces an Antifragile system—the Omega-Shield V6.2—which utilizes a multi-stage, inhaled mRNA-LNP delivery method to achieve sterile mucosal immunity. The proposed architecture is structured around several key innovations: The Arboreal-Rhizomatic (A-R) Hybrid Synergy: Rather than replacing the existing BCG vaccine, the Omega-Shield acts as a "Rhizomatic" booster anchored by the BCG "Trellis," which maintains the established 100-year safety foundation for neonatal priming. The "Triad Engine" Architecture: The system targets the three-part life cycle of Mtb—infiltration (encoding ESAT-6/CFP-10), persistence (targeting DosR regulon antigens), and transmission (targeting resuscitation-promoting factors) to block pathogen reactivation. The "Taming" Protocol (Bio-Digital Rheostat): To prevent immunopathology and lung cavitation, the architecture features a load-triggered IL-10 synthetic promoter that acts as a "Biological Brake," automatically damping inflammation based on real-time cytokine distress signals. Engineering for Global Health Security: The vaccine utilizes a "Glassy Matrix" substrate (Spherical Lipid-Stabilized Nanoparticles embedded in Sucrose/Trehalose) to achieve 8-week stability at 4°C, removing the need for ultra-cold chain infrastructure in low-resource environments. Advanced Modeling and R&D: The architecture is developed using a Holistic System Modeling Engine (MMSH), a high-fidelity digital twin that anchors data in physical reality to prevent "hallucination". The document outlines a hardened R&D falsification loop, including 10,000 parallel simulations and TRIZ-based "Periodic Action" for in vivo calibrat By transitioning from "Fragile Medicine" to Antifragile Architecture, OMEGA-GENESIS seeks a deterministic end to the TB epidemic through a system constitutionally bound to protect both host integrity and systemic stability.