The Ongoing Journey of a Shigella Bioconjugate Vaccine

Abstract

Shigellosis is a serious disease with a major impact, especially in low-income countries where mortality and morbidity are high. In addition, shigellosis among travelers and military personnel is a cause of significant morbidity and contributes to the increase in antimicrobial resistance. The World Health Organization (WHO) considers the development of a Shigella vaccine a priority for public health. Over the past 60 years, several efforts to develop a Shigella vaccine have been pursued, without success. The principle of preventing shigellosis with a conjugate vaccine was demonstrated in the 1990′s, but this vaccine was not further developed. Bioconjugation is an innovative technology that allows the production of conjugate vaccines in a biological environment to preserve native immunogenic structures. In this review, we describe the journey of the bioconjugate Shigella vaccine, one of the most advanced clinical programs for a Shigella vaccine.

Promising directions for vaccine development to prevent shigellosis

“…На основании 1130 изученных случаев шигеллезов, S. Livio с соавт. [24] Основные направления исследований касаются создания: цельноклеточных (живых аттенуированных [26][27][28][29][30][31], инактивированных [32]), субъединичных полисахаридных (неконъюгированных [33], конъюгированных [34][35][36][37]) и белковых вакцинных кандидатов, в том числе препаратов нового поколения: частицы внешних мембран Shigella spp., созданных на основе генетически модифицированных бактерий и состоящие из липополисахаридов, белков и растворимых периплазматических компонентов, полученных с помощью технологии GMMA (Generalised Modules for Membrane Antigens) [38,39]; мультикомпонентный вакцинный комплекс рекомбинантных IpaB-и IpaC-белков и липополисахаридов Shigella spp. [40,41].…”

“…до 5 лет при отсутствии серьезных нежелательных явлений [34]. Испытания полисахаридных вакцин против шигеллеза, полученных с применением технологии биоконъюгации, продемонстрировали иммуногенные и протективные свойства данного типа препаратов [35]. В КИ фазы II, проведенных компанией LimmaTech Biologics AG (Швейцария) с участием лиц в возрасте 18-45 лет, показано, что эффективность защиты кандидатной биоконъюгированной вакцины Flexyn2a против тяжелого протекания заболевания составила 72,4% [36].…”

Chemical Synthesis and Antigenicity Evaluation of Shigella dysenteriae Serotype 10 O-Antigen Tetrasaccharide Containing a (S)-4,6-O-Pyruvyl Ketal

“…7 Although Shigella vaccine candidates based on whole-cell, glycoconjugate, and generalized modules for membrane antigens (GMMA) are in clinical trials, no licensed vaccine is available yet. 8,9 The most advanced ongoing clinical programs are those with O-antigenbased glycoconjugate candidates. Since the early 1990s, Robbins et al have proven that the O-antigens of S. dysenteriae serotype 1, 10,11 S. flexneri serotypes 2a 12,13 and 6, 14 and S. sonnei 15−17 are promising antigens for the development of a Shigella vaccine.…”

“…18 A quadrivalent bioconjugate vaccine (S4V), which carries Oantigens of S. flexneri serotypes 2a, 3a, and 6 and S. sonnei bioconjugated to the rEPA, has entered a phase 1/2 clinical trial in Kenya. 8 Since key epitopes may be altered and labile substitutions may not survive the process of polysaccharide isolation, well- defined synthetic oligosaccharides have been invaluable tools to the growing field of glycoconjugate vaccine development. 19,20 Oligosaccharides corresponding to the O-antigens of S. dysenteriae serotypes 1, 21,22 3, 23 4, 24,25 5, 26 and 8, 27 S. flexneri serotypes 1, 28 2, 29 3, 30,31 4, 32 5, 33 and 6 34 as well as S. sonnei 35,36 44 In the course of our studies directed toward the synthetic carbohydrate-based antibacterial vaccine, we are particularly concerned about the roles of various functional groups in immunological activities of bacterial glycans.…”

“…Developing a Shigella vaccine is considered as a public health priority by the World Health Organization . Although Shigella vaccine candidates based on whole-cell, glycoconjugate, and generalized modules for membrane antigens (GMMA) are in clinical trials, no licensed vaccine is available yet. , The most advanced ongoing clinical programs are those with O-antigen-based glycoconjugate candidates. Since the early 1990s, Robbins et al have proven that the O-antigens of S.…”