Length of the linker and the interval between immunizations influences the efficacy ofVibrio choleraeO1, Ogawa hexasaccharide neoglycoconjugates

Abstract

Ogawa hexasaccharide neoglycoconjugates induce protective antibodies in mice. Similar Ogawa conjugates but with a longer linker that connects the carrier to shorter saccharides are immunogenic, but generally ineffective at inducing vibriocidal or protective antibodies. The efficacy of Ogawa hexasaccharide neoglycoconjugates of different linker lengths were tested. The majority of mice given immunizations separated by a 14-day gap did not produce vibriocidal or protective antibodies. Mice immunized 28 days apart with immunogens containing the shortest or medium length linker, but not the longest, produced vibriocidal and protective antibodies. A nonprotective, priming dose of purified Ogawa LPS followed 5 days later with a booster of the Ogawa neoglycoconjugates (di-, tetra-, or hexasaccharide) resulted in vibriocidal antibodies at day 10.

Identification of the Smallest Structure Capable of Evoking Opsonophagocytic Antibodies against Streptococcus pneumoniae Type 14

“…Our findings (28) and the work of others (7,8,27,33) on synthetic oligosaccharide-protein conjugates should encourage more research on synthetic oligosaccharide-conjugate vaccines. Establishing whether animals and humans can produce antibodies against minimal synthetic oligosaccharides, however, is just the first step in the development of a synthetic pneumococcal vaccine.…”

“…Synthetic carbohydrate-based vaccines are being investigated by many researchers for the prevention of diseases caused by Streptococcus pneumoniae (12), Haemophilus influenzae type b (7,33), meningococcus group C (8), Vibrio cholerae (27), etc. Advantages of synthetic carbohydrate-based vaccines include their well-defined chemical structures (chain length, epitope conformation, and carbohydrate/protein ratio) and a lack of the impurities present in polysaccharides obtained from bacterial isolation (4).…”

Multimeric bivalent immunogens from recombinant tetanus toxin HC fragment, synthetic hexasaccharides, and a glycopeptide adjuvant

“…Consequently, individual or series [19] of tailor-made neoglycoconjugates with predetermined carbohydrate ratio can be prepared. Indeed, we have successfully prepared a large number of such constructs using the above methods and techniques [20][21][22][23][24]. Extrapolating on the above, we should be able to use these techniques to prepare conjugates having more than one synthetic carbohydrate chemically attached to a protein carrier, and determine the average molar content of each of the antigens attached per mole of the carrier.…”

The Future of Synthetic Carbohydrate Vaccines: Immunological Studies on Streptococcus pneumoniae Type 14

“…In 2004, Verez Bencomo et al, reported the large-scale synthesis and the introduction of a synthetic oligosaccharide vaccine for Haemophilus influenzae type b for use in humans in Cuba [9]. The immunogenicity of the synthetic oligosaccharide fragment of the O-specific polysaccharide (O-PS) of Vibrio cholera O1, serotype Ogawa, conjugated to bovine serum albumin has been investigated in a mouse model [62,63]. A multimeric bivalent synthetic hexasaccharide fragment of the O-specific polysaccharide of Vibrio cholera O 1 , s e r o t y p e O g a w a , i n combination with Inaba:1 or a synthetic disaccharide tetrapeptide peptidoglycan fragment as adjuvant were prepared and conjugated to recombinant tetanus toxin H(C) fragment as protein carrier [64].…”