Analysis of current regulatory requirements for the quality of live bacterial vaccines and prospects for the improvement of vaccine quality control methods

INTRODUCTION. Currently, there are live bacterial vaccines (LBVs) for the prevention of tuberculosis and particularly dangerous infections, such as plague, tularaemia, anthrax, and brucellosis. LBVs provide reliable and long-lasting protection. The high effectiveness of LBVs is due to their ability to mimic natural infections. Despite significant differences in LBV compo­sitions, indications, and production species, the applicable quality control approaches share some common principles. At the same time, there are significant differences in methodological approaches to the assessment of a number of quality attributes, and some of these approaches require improvement and/or optimisation. AIM. This study aimed to analyse current regulatory requirements for the quality of LBVs having different compositions and indications, to identify the quality attributes of LBVs with the associated quality control methods in need of improvement, and to explore promising pathways for further development in this area. DISCUSSION. The review of regulatory standards and manufacturer specifications identified several quality attributes common to all LBVs. Vaccine identity was considered a key quality attribute. Motivated by the development of novel national diagnostic test systems, the authors analysed the performance of these test systems in practice to determine their potential for the identification of bacterial vaccines. In particular, immunochromatographic and serological techniques were successfully applied to the quality control of the tularaemia vaccine, a serological method was deemed suitable for brucellosis vaccines, and immunochromatography was recommended for plague and anthrax vaccines. A multiplex PCR method passed practical testing to be used for the quality control of BCG vaccines with reagents from Russian manufacturers. Flow cytometry was considered a promising technique for improving the quality control of LBVs in terms of viable units (tuberculosis and plague vaccines) and immunogenicity (plague vaccines). CONCLUSIONS. This analysis of regulatory requirements highlighted problematic issues related to the standardised quality attributes of LBVs and methods for their assessment. The literature review results and the authors’ own data indicate promising directions for improving the methodology of LBV quality assessment. One of these promising directions is the use of Russian-made commercial test systems for LBV identification.