Therapeutic Vaccines: Why Have They Succeeded in Some Diseases and Failed in Others?
Keywords:
Vaccines, Therapeutic, Immunotherapy, Antigens, Neoplasm Immune Tolerance, T-Lymphocyte Exhaustion, Tumor Microenvironment, BiomarkerAbstract
Therapeutic vaccines generate or restore antigen-specific immunity, providing a unique clinical approach as compared to prophylactic vaccination. Although therapeutic vaccines have intermittent efficacy in different diseases, their optimistic response is reported in some infectious diseases whereas, insignificant efficacy in many chronic and immune-dysregulated malignancies. This questions the underlying biological and translational determinants and seek scientific explanations for these divergent outcomes. Therapeutic vaccines have been linked with well-characterized conserved target antigens, partially preserved immune competence, and disease settings that allow effective immune activation., which predetermines the success of therapeutic vaccines. In contrast, failure of these vaccines is often associated with antigenic variability, immune exhaustion or tolerance, prevailing immunosuppressive mechanisms, and recalcitrant disease microenvironments that impair effective immune interactions. Additional complications include vaccine platforms, poor adjuvants as well as concerns related to design of clinical trials like poor endpoints and poor patient stratification. Immunology, biomolecular profiling and vaccine engineering technologies have elucidated these challenges and identified ways of overcoming them. The translational efficacy can be improved by integrating therapeutic vaccines with immune-modulating factors, selection of targeted antigens, and the use of biomarkers to guide the clinical process. It is essential to define success and failure to guide the development of next-generation therapeutic vaccines rationally.
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Copyright (c) 2026 Mubashra Inam, Kiran Rehman, Rabiya Atta (Author)
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