Safety and immunogenicity of a synthetic carbohydrate conjugate vaccine against Shigella flexneri 2a in healthy adult volunteers: a phase 1, dose-escalating, single-blind, randomised, placebo-controlled study

Antibodies Elicited by the Shigella sonnei GMMA Vaccine in Adults Trigger Complement-Mediated Serum Bactericidal Activity: Results From a Phase 1 Dose Escalation Trial Followed by a Booster Extension

“…Other Shigella live-attenuated and conjugate vaccine candidates also elicited robust SBA titers in healthy adults following vaccination (21,24), comparable with titers of individuals from endemic regions who acquire immunity following natural exposure (42). In a recent controlled human infection model, a challenge dose of S. sonnei 53G induced LPSspecific serum IgG and IgA antibodies with S. sonnei-specific bactericidal activity (43).…”

“…Therefore, current vaccine development strategies against Shigella mostly target the serotype-specific OAg of the bacteria. Several vaccine candidates, developed using different techniques, are under investigation (21)(22)(23)(24)(25), but no vaccine is widely available. However, the morbidity of the disease coupled with the rise of antimicrobial resistance (26,27) urges for the introduction of an effective vaccine.…”

The Shigella Type III Secretion System: An Overview from Top to Bottom

“…Likewise, the inactivated Shigella vaccines and live-attenuated vaccines mentioned above elicit immune responses that favor targeting the most abundant available antigen, which is the surface-exposed LPS [ 167 , 169 , 170 ], which necessitates the creative generation of multivalent formats. The first subunit vaccines against Shigella included conjugates of Shigella O antigens with recombinant exoprotein A (rEPA) which was initially developed in Israel [ 171 ] and is being developed to recognize multiple serotypes using synthetic carbohydrate species [ 172 ]. Another approach has involved subunitlike vaccines targeting the Shigella T3SS that were generated from soluble extracts of the bacteria that contained large amounts of LPS and significant quantities of several different proteins, including the tip complex and translocator proteins IpaB, IpaC and IpaD [ 173 ].…”

Exploratory N‐Protecting Group Manipulation for the Total Synthesis of Zwitterionic Shigella sonnei Oligosaccharides

“…It is noteworthy that this strategy was originally investigated in our group to tackle a Shigella flexneri 2a infection [9] . A vaccine candidate featuring a 15‐mer oligosaccharide hapten—a trimer analogue of the biological repeating unit of the S. flexneri 2a O‐antigen (O‐Ag)—linked to a protein carrier via single point attachment was proposed, [10] and more recently demonstrated to be safe and strongly immunogenic in adult volunteers [11] . Now paying attention to the second most prevalent Shigella serotype, we report herein our exploratory work and successful achievements on the chemical synthesis of oligomers of the repeating unit from the S. sonnei O‐Ag, a unique zwitterionic polysaccharide (ZPS).…”

“…Similarly to the strategy implemented to achieve the first synthetic glycan‐based Shigella vaccine candidate that has reached clinical evaluation, [11] the availability of the di‐, tetra‐, hexa‐ and octasaccharides ( 1 – 4 )—herein synthesized as their propyl glycoside—and the feasibility of larger well‐defined fragments of the S. sonnei ZPSs pave the way to detailed molecular investigation. Epitope mapping, [31–32] supported by thorough conformational and structural analysis, [31, 32b,c, 33] will contribute to unravel the molecular attributes governing antigenic mimicry of the bacterial polysaccharide antigens by short synthetic oligosaccharides as a step forward to a structure‐guided design of a S. sonnei synthetic glycan conjugate vaccine [34]…”