Saccharide/protein conjugate vaccines for Bordetella species: Preparation of saccharide, development of new conjugation procedures, and physico-chemical and immunological characterization of the conjugates

Abstract

Bordetellae are Gram-negative bacilli causing respiratory tract infections of mammals and birds. Competitive inhibition assays showed the immunodominance of the non-reducing end of these O-SP. Conjugates of B. bronchiseptica and B. parapertussis O-SP were prepared by two methods: using the Kdo residue exposed by mild acid hydrolysis of the LPS or the core glucosamine residue exposed by deamination of the LPS, for binding to an aminooxylated protein. Both coupling methods were carried out at a neutral pH, room temperature, and in a short time. All conjugates, injected as saline solutions at a fraction of an estimated human dose, induced antibodies in mice to the homologous O-SP. These methodologies can be applied to prepare O-SP-based vaccines against other Gramnegative bacteria.

The O Antigen Is a Critical Antigen for the Development of a Protective Immune Response to Bordetella parapertussis

“…These results are not necessarily easily translated to improved human vaccines, since vaccine reactogenicity has been associated with LPS of B. pertussis. However, B. parapertussis LPS is less stimulatory toward TLR4 than B. pertussis LPS, and it is possible to purify the O antigen portion of the LPS (20,26,55), thereby removing the TLR4 agonist, lipid A, to which is attributed most of the proinflammatory stimulation (32). Alternatively, other, as-yet-unidentified antigens of B. parapertussis may prove to be protective and could be added to acellular whooping cough vaccines.…”

Synthesis, characterization, and immunogenicity in mice of Shigella sonnei O-specific oligosaccharide-core-protein conjugates

“…The finding that the identity of the sugar residue positioned at the nonreducing end of the synthetic S. dysentariae type 1 oligosaccharide conjugates is an important variable for the immunogenicity of these conjugates (14) points to the importance of the end groups in general in the immune response and may provide an explanation for the superior immunogenicity of the O-SPC and synthetic oligosaccharide conjugates over O-SP conjugates; the former have more end groups. The importance of the terminal saccharide was also demonstrated for Bordetellae conjugates prepared the same way, where the terminal reducing end was immunodominant (11). This method is being studied with S. flexnerii 2a and 6 LPS.…”

A Synthetic Carbohydrate-Protein Conjugate Vaccine Candidate against Shigella flexneri 2a Infection

“…LPS-detoxification is a prerequirement to the development of LPS-based conjugate vaccines. Despite this difficulty, vaccine candidates derived from LPS lacking full-length lipid A-chains are under investigation (2)(3)(4)(5)(6). Alternatively, progress in glycochemistry has opened the way to third generation polysaccharide vaccines, namely, synthetic carbohydrate-protein conjugate vaccines (7)(8)(9)(10).…”