Search

Scientific relevance. Currently, only the rabbit pyrogen test is used to test the Vianvac® typhoid Vi polysaccharide vaccine for pyrogenicity. As part of the product specification file, the gel-clot test for bacterial endotoxins (BE) will improve the reliability of quality control, as well as harmonise the requirements for the vaccine with the requirements outlined for this group of medicinal products by leading world pharmacopoeias.Aim. This study aimed at an experimental assessment of the applicability of the gel-clot test to the quantification of BE in the typhoid Vi polysaccharide vaccine.Materials and methods. This study used samples from 5 batches of the typhoid Vi polysaccharide vaccine (0.5 mL/dose, solution for subcutaneous injection), LAL and TAL reagents. The analysis included the gel-clot test and the pyrogenicity test according to the State Pharmacopoeia of the Russian Federation (OFS.1.2.4.0006.15 and OFS.1.2.4.0005.15, respectively).Results. According to calculations, the BE limit for the tested vaccine was 96 EU/mL, and the maximum valid dilution (MVD) was 3200. The authors determined the regulatory requirements for typhoid Vi polysaccharide vaccine quality in terms of BE (not more than 48 EU/dose). The in vitro BE tests were positive at vaccine dilutions of 1/16 to 1/32 and negative at 1/64 to 1/256. The authors selected and validated a working vaccine dilution of 1/128. The BE content measured in the tested samples ranged from 0.24 to 0.48 EU/dose. The in vivo pyrogen tests were positive at dilutions of 1/16 to 1/128 and negative at 1/256 in all experiments with samples from 5 vaccine batches at dilutions ranging from 1/16 to 1/256.Conclusions. This study has experimentally proven that the gel-clot test can quantify BE in the typhoid Vi polysaccharide vaccine. The authors have recommended introducing the gel-clot BE test in the monograph of the State Pharmacopoeia of the Russian Federation on the typhoid Vi polysaccharide vaccine (FS.3.3.1.0012.15).

Shigellosis (bacterial dysentery) is an acute infectious disease caused by Shigella spp., members of the Enterobacteriaceae family. The disease has the highest mortality rate amongst bacterial enteric infections. A considerable proportion of Shigella infections occur in children under the age of five. In 2017, WHO included Shigella spp. strains into the list of “priority pathogens” that are resistant to most antibiotics and pose a threat to global public health. This provided a stimulus for the development of new antibiotics to treat shigellosis. Apart from the creation of new antimicrobial therapies for Shigella infections, an important role in fighting against shigellosis belongs to the preventative measures set out in WHO’s Immunisation Agenda 2030. These include sanitation, hygiene, consumption of clean water, and vaccination. The development of Shigella vaccines has been a priority of the WHO programme for more than 20 years. The aim of the study was to analyse promising approaches to Shigella vaccine development. According to the analysis of literature, only one vaccine against shigellosis has been approved so far—Shigellvac, the Russian polysaccharide dysentery vaccine against Shigella sonnei. This study covers a number of vaccine candidates (whole-cell, polysaccharide, polysaccharide conjugate, protein antigen-based vaccines, etc.) that are at different stages of clinical trials. The importance of researching combination (multivalent) vaccines against Shigellа spp. and other enteric pathogens is noted. However, the authors consider subunit vaccines based on Ipa proteins, providing broad cross-protection against Shigellа spp., and conjugate polyvalent vaccines for children under 5 the most promising for further development.

Typhoid fever is an acute infectious disease caused by Salmonella enterica subsp. enterica serovar Typhi (S. Typhi), which is still extremely common in endemic low- and middle-income countries of Asia and Africa. Industrialised countries may also be affected by typhoid fever outbreaks due to booming international tourism, and natural disasters. Given S. Typhi progressive resistance to antibiotics, high epidemiological burden, and lack of adequate sanitation and hygiene in a number of regions, the introduction of new treatment protocols and the improvement of preventive vaccination are critical tasks in global healthcare. The aim of the study was to highlight the main historical aspects of the typhoid vaccine development, to summarise data on the licensed vaccines and promising approaches to the development of new typhoid vaccines. The paper describes the current epidemiological situation of typhoid fever globally and in the Russian Federation. It dwells upon the global experience in typhoid vaccine development from the production of an inactivated vaccine to the development of conjugated vaccines. The paper summarises data on Russian and foreign-made typhoid fever vaccines currently available in the global pharmaceutical market. It outlines the main trends in the development of vaccines against the disease caused by S. Typhi. The paper demonstrates the need for improving the efficacy of existing vaccines and development of new typhoid combination vaccines.