Personalized mRNA Vaccines Encoding Patient-Derived HIV-1 Envelope Trimers: An In Silico Proof-of-Concept Study in Multidrug-Resistant HIV Infection

This study develops and evaluates a computational pipeline for designing fully personalized mRNA vaccines for individuals with multidrug-resistant HIV-1 infection. Patient-specific viral envelope (Env) sequences are reconstructed, optimized, and encoded into individualized mRNA constructs formulated in lipid nanoparticles. HLA-restricted epitope prediction identifies personalized CD4⁺ and CD8⁺ T-cell targets, and agent-based immune modeling predicts robust T-cell expansion following vaccination. All analyses are conducted using synthetic patient data and in-silico simulations. The results demonstrate the technical feasibility and potential clinical relevance of patient-tailored HIV immunotherapy, supporting future experimental validation.