Therapeutic Vaccines for Chronic Viral Infections: From Immune Modulation to Clinical Translation.

Therapeutic vaccines are a key strategy to achieve the goal of "functional cure" of chronic viral infections, including hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), human papillomavirus (HPV), and Epstein-Barr virus (EBV). Various platforms (such as viral vectors, nucleic acid vaccines, recombinant proteins, etc.) have successfully induced strong virus-specific T-cell responses in early trials, but their clinical efficacy is still limited by the immunosuppressive environment formed by the host. The core bottlenecks are severe T-cell exhaustion, viral immune escape, and various forms of local immune tolerance. Therefore, the field is moving toward combination therapies, including reduction of viral load, targeting of immune activation, and inhibition of inhibitory signaling pathways. This article summarizes the preclinical and clinical progress of therapeutic vaccines in the past decade, analyzes the major challenges in vaccine development, and discusses the future development directions in this field.