Robert A. Pon

Polysialic Acid Bioengineering of Cancer and Neuronal Cells by N -Acyl Sialic Acid Precursor Treatment

N-acetyl neuraminic acid, the most prominent member of the acidic sugar family known as sialic acids, is ubiquitous on the surface of eukaryotic cells where, as a glycoconjugate substituent, it is involved in numerous important biological processes. Polysialic acid (PSA), an α-(2-8)-linked homopolymer of N-acetyl neuraminic acid, is equally as important biologically; however, its expression is more restricted to embryonic tissues [1], regions of brain plasticity [2], and as an oncofetal antigen in several cancers of neuroectodermal origin [3, 4]. PSA, by virtue of its large polyanionic charge, functions as an antiadhesive, thereby negatively regulating cell–cell interaction, and is implicated in cell migration [5–8]. The limited expression of PSA in normal adult tissue increases its potential as a cancer determinant, where it has been found in abundance in such malignancies as Wilms’ tumor [9], small cell and nonsmall cell lung cancer [10, 11], neuroblastoma [12], and rhabdomyosarcoma [13]. Several lines of evidence further implicate the antiadhesive nature of PSA with primary tumor shedding and metastasis [14–16], where its expression is negatively associated with favorable prognoses [10].

Chapter 48 – Bacterial polysaccharide vaccines: Glycoconjugates and peptide-mimetics

Publisher Summary The early discovery that the capsular polysaccharides (CPS) of pneumococci were immunogenic in humans was an important development in vaccine technology, which eventually led to the licensing of polysaccharide vaccines against human bacterial diseases, such as Neisseria meningitidis (groups A, C, W-135, and Y), Streptococcus pneumoniae (23 serotypes), Haemophilus influenzae type b, and Salmonella enterica sv. Typhi. The use of bacterial capsular polysaccharides as vaccines in healthy adults has been established for several decades. However, the populations most at risk, children under the age of five years old and the immunocompromised, respond poorly to them and are thus inadequately protected against invasive bacterial disease. The simple act of conjugating capsular polysaccharides to protein carriers in large part overcomes many of these limitations and has realized the rapid development of conjugate vaccine technology. This review focuses on the current technology used in the preparation of glycoconjugate vaccines, their application and effectiveness toward bacterial pathogens of the highest importance and the state of the new generation of synthetic and peptide mimetic vaccines that are targeted to bacterial capsular polysaccharide antigens.

Bacterial polysaccharide vaccines: Glycoconjugates and peptide-mimetics

Publisher Summary The early discovery that the capsular polysaccharides (CPS) of pneumococci were immunogenic in humans was an important development in vaccine technology, which eventually led to the licensing of polysaccharide vaccines against human bacterial diseases, such as Neisseria meningitidis (groups A, C, W-135, and Y), Streptococcus pneumoniae (23 serotypes), Haemophilus influenzae type b, and Salmonella enterica sv. Typhi. The use of bacterial capsular polysaccharides as vaccines in healthy adults has been established for several decades. However, the populations most at risk, children under the age of five years old and the immunocompromised, respond poorly to them and are thus inadequately protected against invasive bacterial disease. The simple act of conjugating capsular polysaccharides to protein carriers in large part overcomes many of these limitations and has realized the rapid development of conjugate vaccine technology. This review focuses on the current technology used in the preparation of glycoconjugate vaccines, their application and effectiveness toward bacterial pathogens of the highest importance and the state of the new generation of synthetic and peptide mimetic vaccines that are targeted to bacterial capsular polysaccharide antigens.