Abstract
The “Generation Gold Standard” (GGS) initiative, launched by NIH and BARDA, seeks to advance pandemic preparedness through β-propiolactone (BPL)–inactivated whole-virus vaccines. While positioned as a transformative platform, GGS relies on legacy technology with known limitations, including waning immunity and limited cross-variant protection, as seen in COVID-19 vaccines such as CoronaVac. This Perspective critiques GGS’s scientific rationale and transparency, arguing that it overlooks recent advances in epitope-based vaccinology, AI-driven design, and systems biology. By prioritizing scalability over immunological precision, GGS risks delaying progress toward more effective, adaptable vaccine platforms. We propose a forward-looking approach that conserved epitope targeting, antigen sequence optimization, multi-omics integration, and transparent preclinical validation to enhance efficacy and public trust. As the window for applying lessons from COVID-19 narrows, redirecting resources toward mechanistically innovative platforms is essential for global health security.