| Anthrax is a fatal zoonotic disease caused by Bacillus anthracis.According to world health organization(WHO)reports,there are 20 000 to 100 000 new reported cases of anthrax globally each year.The light-weight and lethal spores can be easily made into biological weapons for war or terrorist attack.Appropriate antibiotic drugs can effectively eradicate Bacillus anthracis in the early stage.However,antibiotics have no effect on the anthrax toxin,which limit their use in the advanced infection when the toxins have risen to a high level.The emerging resistant strains caused by antibiotics have brought unprecedented challenges.Therefore,prevention strategies are more important than treatments for anthax control,in which vaccination is the most cost-effective way.The traditional anthrax vaccines mainly include attenuated live anthrax vaccine,Anthrax Vaccine Adsorbed(AVA)and Anthrax Vaccine Precipitated(AVP).These vaccines have some drawbacks,such as the unclear chemical composition,unstable yield,low immune efficacy,dosage difficult to control and high incidence of adverse reactions.Hence,the development of new anthrax vaccines if of great clinical importance and huge market demands.Anthrax toxin and capsule are two main virulence factors for pathogenicity of anthrax bacillus.Anthrax capsular polysaccharide plays decisive roles in growth and development of infection,including roles of the barrier,adhesion,and resistance to drug.Many specific polysaccharide structures located in vegetative cell wall of Bacillus anthracis come to be the targets of early diagnosic tool and vaccines development.According to recently studies,there is a highly conservative specific oligosaccharide antigen in Bacillus anthracis capsule,which could be an ideal target for vaccine.However,polysaccharide vaccine is reported with poor immunogenicity and high incidence of T cell-independent antibody response.It is proved that conjugations of oligosaccharides with carrier proteins show improved immunogenicity and convert polysaccharides into T cell dependent antigens.Recently,glycoprotein conjugates with high immunogenicity come to be the focus of vaccine development,and tens of glycoprotein vaccines have been used in clinic.We efficiently synthesized monosaccharide donor(3,11,and 17)and monosaccharide acceptor(5,7)from raw materials of glucose,galactose and glucosamine hydrochloride through a concise chemical synthesis strategy with protecting groups of acetyl,benzyl and p-methoxyphenyl.The four oligosaccharide fragments were synthesized via consecutive glycosylation of thioglycosides,include Aminoethyl-?-D-galactopyranosyl-(?1?3)-2-deoxy-2-acetamido-?-D-glucopyranosi de,Aminoethyl-?-D-galactopyranosyl-(?1?6)-(?-D-galactopyranosyl)-(?1?3)-2-deoxy-2-acetamido-?-D-glucopyranoside,Aminoethyl-2-deoxy-2-acetamido-?-D-glucopyranosyl-(?1?6)-(?-D-galactopyranos yl)-(?1?3)-2-deoxy-2-acetamido-?-D-glucopyranoside and Aminoethyl-?-D-glucopyranosyl-(?1?4)-(?-D-galactopyranosyl)-(?1?3)-2-deoxy-2-acetamido-?-D-glucopyranoside.We used glutaraldehyde to conjugate the four oligosaccharide fragments to keyhole limpet hemocyanin(KLH)or bovine serum albumin(BSA).Then we obtained eight glycoprotein conjugates,include TM-1,TM-2,TM-3,TM-4 TM-5,TM-6,TM-7,TM-8.The structures of target compounds and key intermediates were confirmed by 1H-NMR,13C-NMR,ESI-MS,HR-QTOF-MS and MALDI-TOF.Preliminary immunological studies on the KLH conjugates revealed that TM-4 and TM-6 could elicit robust antibody responses in mic,thus verifying the potential of the oligosaccharides for vaccine development and other immunological studies. |
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