Standardized neutralizing antibody assay for Coxsackievirus A10 in clinical trial: A framework for multivalent hand, foot, and mouth disease vaccine evaluation

Abstract

Enteroviruses (EVs) are the major etiological agents of hand, foot, and mouth disease (HFMD), which could lead to severe complications and even fatalities. Owing to the alternating or co-circulation of multiple EV serotypes and the lack of cross-protection, global institutions are pursuing the development of multivalent HFMD vaccines. Notably, the advancement of innovative multivalent HFMD vaccines into the clinical stage highlights the urgent need for a standardized platform to assess immunogenicity. In accordance with international regulatory guidelines, a standardized neutralizing antibody (NtAb) assay for CV-A10 is established through rigorous selection and systematic optimization of key assay components, representing the first such assay tailored for clinical immunogenicity evaluation of CV-A10-based vaccines. By integrating the 1st Chinese National Standard (NS) for CV-A10 NtAb and a standard detection virus, this assay exhibits enhanced detection sensitivity and significant reduction in the inter-laboratory geometric coefficient of variation (GCV), thereby providing a robust, reliable, and transferable platform. This assay facilitates accurate evaluation of multivalent HFMD vaccine efficacy, improves comparability across different vaccine products and provides genuine efficacy in real-world, serving as a valuable reference for global regulatory authorities.