WHO/BS/2019.2362 WHO 1st IS for Enterovirus A71 inactivated vaccine

Overview

Enterovirus A71 (EV71) is the major causative agent of severe and fatal hand, foot and mouth disease (HFMD). Neurological complications induced by EV71 have become a serious public health problem in the Asia-Pacific Region. For this reason, vaccines for the effective prevention of HFMD caused by EV71 have been licensed and several others are under development across the region. The 1 st WHO International Standard (IS) for anti-human enterovirus EV71 serum (Human) was established in 2015 to ensure that methods used to measure the serum neutralizing activity or antibody levels against EV71 are accurate, sensitive and reproducible.

A new collaborative study, reported here, was conducted with an aim to establish the 1st WHO IS for EV71 inactivated vaccine. Four candidate EV71 samples were provided by three different manufacturers and analysed by fourteen laboratories using their in-house ELISA method and a common method (designed by NIBSC and NIFDC) alongside a low titre vaccine sample. The Chinese National Standard (NS) for EV71 inactivated vaccine was also included in the study since it was the only reference available with an assigned potency value.

Within laboratory repeatability and between laboratory reproducibility were generally very good. There was largely good agreement between laboratories in EV71 antigen potency estimates whichever candidate was chosen as a standard and as a result all four candidate samples were found to be suitable as an IS. Candidate 18/116 is proposed as the 1 st IS for EV71 inactivated vaccine because of the larger number of ampoules available, absence of detectable bacterial contamination and for showing as good or better overall results than the other candidates in terms of assay validity, within and between laboratory variability and thermal stability profiles. Candidates 18/120 and 18/156 are proposed as WHO Reference Reagents. These candidate standards have only been validated for use in in vitro assays to measure whole virus antigen content. A second phase of the study should include the evaluation of these samples for use in in vivo potency assays. Assays and reagents to specifically measure the quantity of empty and full virus particles present in EV71 vaccines and analysis of their relative contribution to the antigenic and immunogenic properties of different EV71 vaccine products will be fundamental to ensure appropriate standardization of EV71 vaccines used globally.