Modulating immunodominance through adjuvants and routes – A commentary on next-generation vaccine design for clinical trial

Abstract

Immunodominance – the preferential recognition of certain epitopes – is a double-edged sword in vaccine development. While it enables strong responses against specific pathogens, it limits breadth and durability, especially against rapidly mutating viruses or bacteria. This commentary discusses how adjuvants and immunization routes actively reshape immunodominant epitope landscapes, based on recent preclinical findings. MRSA antigens (Hla,SEB,LuKG,IsdB and MntC), Klebsiella pneumoniae FimA, and SARS-CoV-2 RBD, showing that adjuvant choice can profoundly alter humoral immunity. These insights might have direct implications for clinical trial design, patient stratification, and the development of broadly protective vaccines. We argue that incorporating immunodominance modulation into early phase clinical evaluations may accelerate the path toward more effective and safer vaccines.