TOTAL SYNTHESIS AND IMMUNOLOGICAL EVALUATION OF SACCHARIDE MOIETIES OF THE LIPOPOLYSACCHARIDE FROM NEISSERIA MENINGITIDIS
申请人:MAX-PLANCK-GESELLSCHAFT ZUR FÖRDERUNG DER WISSENSCHAFTEN E.V.
公开号:US20140234364A1
公开(公告)日:2014-08-21
The present invention relates to the total chemical synthesis of the monosaccharide 35
#
(R′═H), the disaccharide 36
#
(R′≠H; R″═H), the trisaccharide 37
#
(R′≠H; R″≠H; R′″≠H) and the tetrasaccharide 1
#
(R′≠H; R″≠H; R′″≠H) of the following general formula wherein R represents —Y—NH
2
Y represents a linker R′ is H or R″ is H or R′″ is H or of the lipopolysaccharide from
Neisseria meningitidis
, as well as to the trisaccharide 37
#
and the tetrasaccharide 1
#
, to vaccines containing at least one of the saccharides 1
#
, 35
#
, 36
#
, and 37
#
and to the use of such vaccine for immunization against diseases caused by infection with bacteria containing the tetrasaccharide α-GlcNAc-(1→2)-α-Hep-(
1→3
)-α-Hep-(1→5)-α-Kdo or the trisaccharide α-Hep-(1→3)-α-Hep-(1→5)-α-Kdo or α-GlcNAc-(1→2)-α-Hep-(1→3)-α-Hep, especially for immunization against meningitis, septicaemia, pneumonia and nasopharyngitis caused by
Neisseria meningitidis.
本发明涉及以下通式中的单糖35#(R' = H)、双糖36#(R'≠H;R"= H)、三糖37#(R'≠H;R"≠H;R'"≠H)和四糖1#(R'≠H;R"≠H;R'"≠H)的全合成,其中R代表-Y-NH2,Y代表连接剂,R'为H或R"为H或R'"为H,以及三糖37#和四糖1#,包含至少其中一种糖的疫苗1#,35#,36#和37#,以及使用这种疫苗免疫预防由于感染含有四糖α-GlcNAc-(1→2)-α-Hep-(1→3)-α-Hep-(1→5)-α-Kdo或三糖α-Hep-(1→3)-α-Hep-(1→5)-α-Kdo或α-GlcNAc-(1→2)-α-Hep-(1→3)-α-Hep的细菌引起的疾病,特别是免疫预防由脑膜炎球菌引起的脑膜炎、败血症、肺炎和鼻咽炎。