title: Immunochemical characterization of synthetic hexa-, octa- and decasaccharide conjugate vaccines for Vibrio cholerae O:1 serotype Ogawa with emphasis on antigenic density and chain length.
abstract: Cholera remains to be a global health problem without suitable vaccines for endemic control or outbreak relief. Here we describe a new parenteral vaccine based on neoglyco-conjugate of synthetic fragments of O-specific polysaccharide (O-SP) of Vibrio cholerae O1, serotype Ogawa. Hexa-, octa- and decasaccharides of the O-SP with carboxylic acid at the reducing end were chemically synthesized and conjugated to tetanus toxoid (TT). The conjugates prepared by a novel linking scheme consisted of 17-atom linker of hydrazide and alkyl bonds elicited robust serum IgG anti-LPS responses with vibriocidal activities in mice. There is a length dependence in immune response with decasaccharide conjugates elicited the highest anti-LPS IgG. There seems to be an indication that regardless of the carbohydrate chain length, a molar ratio of 230 ± 10 monosaccharide units per TT induced high antibody response. The conjugates also elicited cross-reactive antibodies to serotype Inaba. The formulation of the proposed cholera conjugate vaccine, similar to other licensed polysaccharide vaccine, is suitable for children immunization. A parenteral cholera vaccine could overcome the diminishing immunogenicity in most of oral vaccines due to the gastrointestinal complexity and environmental enteropathy in children living in impoverished environment and could be considered for global cholera immunization.
authors: Eunice Kennedy Shriver National Institute of Child Health & Human Development, National Institutes of Health, Bldg. 6, Room 1A06, 9000 Rockville Pike, Bethesda, MD, 20892, USA.
authors: Peter
authors: P
authors: Ftacek
authors: Victor
authors: V
authors: Nelson
authors: Shousun C
authors: SC
authors: Szu
mesh_terms: D000907:Antibodies, Bacterial / Q000276:immunology; D001428:Bacterial Vaccines / Q000737:chemistry* / Q000276:immunology; D006023:Glycoproteins / Q000737:chemistry / Q000276:immunology; D008070:Lipopolysaccharides / Q000737:chemistry* / Q000276:immunology; D018074:Vaccines, Conjugate / Q000737:chemistry / Q000276:immunology; D014734:Vibrio cholerae / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D006023:Glycoproteins; D008070:Lipopolysaccharides; D018074:Vaccines, Conjugate
references: Carbohydr Res. 1997 May 19;300(4):329-39
references: 9210300
references: J Clin Invest. 1975 Mar;55(3):551-60
references: 803978
references: Carbohydr Res. 1982 Mar 1;100:341-9
references: 7083255
references: Infect Immun. 1970 Jan;1(1):80-7
references: 16557700
references: Expert Rev Anti Infect Ther. 2012 Apr;10(4):435-44
references: 22512753
references: Bull World Health Organ. 1968;39(2):247-59
references: 5303406
references: J Biol Chem. 1998 Jan 30;273(5):2777-83
references: 9446585
references: Lancet. 1973 Jun 2;1(7814):1230-2
references: 4122574
references: Microbiology (Reading). 1999 Sep;145 ( Pt 9):2477-2484
references: 10517600
references: J Microbiol Methods. 2003 Dec;55(3):745-53
references: 14607417
references: Vaccine. 2011 Sep 2;29(38):6498-504
references: 21767596
references: PLoS Negl Trop Dis. 2011 Oct;5(10):e1289
references: 22028938
references: Emerg Infect Dis. 2011 Nov;17(11):2105-12
references: 22099114
references: Bull World Health Organ. 2012 Mar 1;90(3):209-218A
references: 22461716
references: FEMS Immunol Med Microbiol. 2006 Jun;47(1):116-28
references: 16706794
references: J Infect Dis. 1970 May;121(5):505-13
references: 4986889
references: Expert Opin Drug Discov. 2011 Oct;6(10):1045-66
references: 22646863
references: J Immunol. 1985 Aug;135(2):1220-31
references: 2409142
references: N Engl J Med. 2013 Feb 14;368(7):599-609
references: 23301694
references: Bull World Health Organ. 1968;38(5):777-85
references: 5303331
references: Carbohydr Res. 1988 May 15;176(2):316-23
references: 3138026
references: J Health Popul Nutr. 2012 Mar;30(1):12-6
references: 22524114
references: N Engl J Med. 2009 Mar 12;360(11):1060-3
references: 19279337
references: Science. 2009 May 15;324(5929):885
references: 19443768
references: Infect Immun. 1991 Dec;59(12):4450-8
references: 1937803
references: J Infect Dis. 1991 Jun;163(6):1235-42
references: 2037789
references: Proc Natl Acad Sci U S A. 1999 Apr 27;96(9):5194-7
references: 10220442
references: Curr Top Med Chem. 2008;8(2):126-40
references: 18289082
references: Science. 2010 Sep 17;329(5998):1462-3
references: 20847246
references: Carbohydr Res. 2005 Oct 17;340(14):2256-69
references: 16098493
references: Clin Diagn Lab Immunol. 2002 Mar;9(2):383-7
references: 11874883
references: J Immunol. 1970 Aug;105(2):431-41
references: 5433700
references: Southeast Asian J Trop Med Public Health. 1986 Dec;17(4):558-66
references: 3576285
references: Carbohydr Res. 1988 Mar 15;174:239-51
references: 2454158
references: Nature. 1951 Jul 28;168(4265):167
references: 14875032
references: Bull World Health Organ. 1968;38(3):359-72
references: 5302329
references: Am J Trop Med Hyg. 2006 Nov;75(5):973-7
references: 17123999
references: Nature. 2011 Aug 24;477(7365):462-5
references: 21866102
references: Infect Immun. 1970 Jul;2(1):29-37
references: 16557795
references: J Infect Dis. 2002 Apr 1;185(7):950-62
references: 11920320
references: J Infect Dis. 1969 Aug;120(2):192-201
references: 5387567
references: Lancet. 2012 Jun 30;379(9835):2466-2476
references: 22748592
references: Glycoconj J. 2000 Jun;17(6):425-33
references: 11294508
references: BMC Biol. 2010 Oct 04;8:129
references: 20920375
references: Lancet. 2009 Mar 21;373(9668):993-4
references: 19330941
references: J Infect Dis. 1970 May;121:Suppl 121:1-9
references: 4912069
references: Infect Immun. 2010 Feb;78(2):764-72
references: 19948836
references: Infect Immun. 2004 Jul;72(7):4090-101
references: 15213154
references: Trans R Soc Trop Med Hyg. 1979;73(1):3-9
references: 442179
references: Vaccine. 2000 May 8;18(22):2399-410
references: 10738097
references: Pediatr Dermatol. 2008 Mar-Apr;25(2):275-6
references: 18429804
references: Lancet. 2010 Aug 21;376(9741):606-14
references: 20692030
references: Infect Immun. 1998 Jul;66(7):3095-9
references: 9632571
references: Carbohydr Res. 2008 Feb 4;343(2):196-210
references: 18048016
references: Carbohydr Res. 1994 Mar 18;256(1):113-28
references: 8194067
references: Infect Immun. 1992 Aug;60(8):3201-8
references: 1639490
references: Clin Vaccine Immunol. 2012 Jun;19(6):842-8
references: 22518009
references: Bioconjug Chem. 2011 Oct 19;22(10):2179-85
references: 21899371
references: Bull World Health Organ. 1968;38(3):335-46
references: 5302923
references: Lancet. 1973 Jun 2;1(7814):1232-5
references: 4122575
references: Indian J Med Res. 2012 May;135(5):678-9
references: 22771600
references: J Infect Dis. 1995 Jun;171(6):1387-98
references: 7769272
references: Biochem Biophys Res Commun. 1993 Jan 15;190(1):302-7
references: 8422256
references: Proc Natl Acad Sci U S A. 2007 Sep 4;104(36):14478-82
references: 17726093