Taxonomic group: bacteria / Proteobacteria
(Phylum: Proteobacteria)
Associated disease: bacillary dysentery (shigellosis) [ICD11:
1A02 
, ICD11:
SA56 , ICD11:
XN7HG ];
infection due to Shigella flexneri [ICD11:
XN7Y2 ]
The structure was elucidated in this paperNCBI PubMed ID: 30670300Publication DOI: 10.1016/j.vaccine.2018.12.067Journal NLM ID: 8406899Publisher: Elsevier
Correspondence: P.G. Aparin <pg.aparin
nrcii.ru>
Institutions: Laboratory of Carbohydrate Vaccines, National Research Center-Institute of Immunology, Federal Medical Biological Agency of Russia, 24, Kashirskoe Shosse, Moscow, Russia, N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 47, Leninsky Prospect, Moscow, Russia, Laboratory of Preparative Biochemistry, National Research Center-Institute of Immunology, Federal Medical Biological Agency of Russia, 24, Kashirskoe Shosse, Moscow, Russia, The Virology and Cellular Immunology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, NIH, Rockville, MD 20852, United States
Shigellosis, a major cause of diarrhea worldwide, exhibits high morbidity and mortality in children. Specificity of Shigella immunity is determined by the structure of the main protective O-antigen polysaccharide component incorporated into the lipopolysaccharide (LPS) molecule. Endotoxicity, however, precludes LPS clinical use. Thus, there is still no vaccine against the most prevalent shigellosis species (serotype S. flexneri 2a), despite ongoing efforts focused on inducing serotype-specific immunity. As LPS is highly heterogenous, we hypothesized that more homogenous pools of LPS might be less toxic. We developed a method to generate a homogenous S. flexneri 2a LPS subfraction, Ac3-S-LPS, containing long chain O-specific polysaccharide (S-LPS) and mainly tri-acylated lipid A, with no penta- and hexa-acylated, and rare tetra-acylated lipid A. Ac3-S-LPS had dramatically reduced pyrogenicity and protected guinea pigs from shigellosis. In volunteers, 50?�g of injected Ac3-S-LPS vaccine was safe, with low pyrogenicity, no severe and few minor adverse events, and did not induce pro-inflammatory cytokines. In spite of the profound lipid A modification, the vaccine induced a prevalence of IgG and IgA antibodies. Thus, we have developed the first safe immunogenic LPS-based vaccine candidate for human administration. Homogenous underacetylated LPSs may also be useful for treating other LPS-driven human diseases. Clinical trial registry: http://grls.rosminzdrav.ru/.
LPS, Shigella flexneri, antibody response, vaccine, Clinically applicable, Homogenous pool, Mucosal immunity
Structure type: oligomer ; 1279.85 [M-H]-
Location inside paper: p.1065, fig.3C, modified Ac4-S-LPS
Compound class: lipid A
Contained glycoepitopes: IEDB_141807,IEDB_151531,IEDB_176772
Methods: 13C NMR, 1H NMR, SDS-PAGE, ELISA, ESI-MS, mild acid hydrolysis, chemical methods, de-O-acetylation, serological methods, GPC, immunization, pyrogenicity assays, immunogenicity evaluation, vaccine immunogenicity
Comments, role: lipid A was obtained by mild acid hydrolysis of partial alkaline deacylation of S-LPS.
Related record ID(s): 1060, 1485, 1487
NCBI Taxonomy refs (TaxIDs): 42897
Show glycosyltransferases
There is only one chemically distinct structure:
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