Recent Advances in HIV Vaccine Development: The Role of mRNA Platforms and Broadly Neutralizing Antibodies

More than four decades after the identification of the human immunodeficiency virus (HIV), the development of an effective preventive vaccine remains one of the most formidable challenges in biomedical science. Unlike many viral pathogens for which classical vaccinology has succeeded, HIV exhibits extraordinary genetic diversity, structural masking of neutralizing epitopes, rapid mutation, early targeting of CD۴⁺ T helper cells, and the establishment of long-lived latent reservoirs. These biological characteristics enable continuous immune evasion and have repeatedly undermined conventional vaccine strategies. Nevertheless, remarkable progress in immunology, structural biology, and biotechnology has significantly advanced the field in recent years. The discovery and characterization of broadly neutralizing antibodies (bnAbs), together with advances in structure-based immunogen design, messenger RNA (mRNA) vaccine platforms, and artificial intelligence (AI)-assisted protein engineering, have provided promising new directions for vaccine development. This review summarizes the major immunological and virological barriers that continue to hinder HIV vaccine efficacy and discusses innovative approaches aimed at overcoming these challenges. Particular emphasis is placed on germline-targeting strategies, stabilized native-like envelope (Env) trimers, sequential immunization regimens designed to guide antibody maturation, and computationally optimized antigens capable of eliciting broader and more durable immune responses. In addition, recent findings from preclinical studies and early-phase clinical trials are highlighted to illustrate the translational potential of these emerging technologies. Collectively, these advances represent a paradigm shift from empirical vaccine development toward precision immune engineering, offering renewed optimism for the design of safe, effective, and broadly protective HIV vaccines in the future

کلیدواژه ها:

HIV Vaccine ، mRNA Vaccine ، Broadly Neutralizing Antibodies (bnAbs)