Role of O-Acetylation in the Immunogenicity of Bacterial Polysaccharide Vaccines

Abstract

The incidence of infectious diseases caused by several bacterial pathogens such as Haemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis, has been dramatically reduced over the last 25 years through the use of glycoconjugate vaccines. The structures of the bacterial capsular polysaccharide (CPS) antigens, extracted and purified from microbial cultures and obtained with very high purity, show that many of them are decorated by O-acetyl groups. While these groups are often considered important for the structural identity of the polysaccharides, they play a major role in the functional immune response to some vaccines such as meningococcal serogroup A and Salmonella typhi Vi, but do not seem to be important for many others, such as meningococcal serogroups C, W, Y, and type III Group B Streptococcus. This review discusses the O-acetylation status of CPSs and its role in the immunological responses of these antigens.

Catalyst-free regioselective acetylation of primary hydroxy groups in partially protected and unprotected thioglycosides with acetic acid

“…[43][44][45][46][47] Bacterial polysaccharides oen contain 6-O-acetyl groups, which play a complex role in the functional immune response. [48][49][50][51] Hence, the development of ways for selective acetylation of unprotected and partially protected carbohydrates would contribute greatly to the study of naturally occurring carbohydrate molecules.…”

A stabilized glycomimetic conjugate vaccine inducing protective antibodies against Neisseria meningitidis serogroup A

“…However, its CRM 197 conjugate elicits in vivo antibodies recognizing the deacetylated polysaccharide but not the natural MenA capsule. Introduction of acetyl esters in the carbaMenA DP8 glycomimetic is demonstrated crucial to improve the MenA polysaccharide mimicry 34,35 , as the CRM 197 conjugate of the Ac-carbaMenA DP8 leads to a high level of functional anti-MenA CPS antibodies, equal to the MenA vaccine benchmark. This work thus presents a proof-of-principle glycomimetic vaccine with activity that matches the conjugate based on the natural polysaccharide.…”

Recent Advances in the Synthesis of Glycoconjugates for Vaccine Development

“…Recent advances in carbohydrate chemistry has opened the way to a third-generation of polysaccharide vaccines, based on the use of synthetic oligosaccharides conjugated to carrier protein. The breakthrough in synthetic vaccines was carried out for H. influenzae type b in 2004, when the Vérez Bencomo research team in Cuba synthesized the first synthetic conjugate vaccine currently available under the trade name Quimi-Hib [ 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , ...…”

“…In addition to these promising findings, the influence of O -acetylation of S. flexneri 2a O-Ag fragments on antigenicity was studied by Mulard group [ 21 ]. Polysaccharide O -acetylation has been shown to play a key role for many pathogens in inducing functional Ab responses [ 22 , 23 , 24 ]. In particular, three diversely O -acetylated S. flexneri 2a O-Ag decasaccharides were synthesized in homogeneous form and their binding to five different protective mAbs was studied, showing some differences in the recognition patterns.…”