Abstract
The glycocalyx, a thick layer of carbohydrates, surrounds the cell wall of most bacterial and parasitic pathogens. Recognition of these unique glycans by the human immune system results in destruction of the invaders. To elicit a protective immune response, polysaccharides either isolated from the bacterial cell surface or conjugated with a carrier protein, for T-cell help, are administered. Conjugate vaccines based on isolated carbohydrates currently protect millions of people against Streptococcus pneumoniae, Haemophilus influenzae type b, and Neisseria meningitides infections. Active pharmaceutical ingredients (APIs) are increasingly discovered by medicinal chemistry and synthetic in origin, rather than isolated from natural sources. Converting vaccines from biologicals to pharmaceuticals requires a fundamental understanding of how the human immune system recognizes carbohydrates and could now be realized. To illustrate the chemistry-based approach to vaccine discovery, I summarize efforts focusing on synthetic glycan-based medicinal chemistry to understand the mammalian antiglycan immune response and define glycan epitopes for novel synthetic glycoconjugate vaccines against Streptococcus pneumoniae, Clostridium difficile, Klebsiella pneumoniae, and other bacteria. The chemical tools described here help us gain fundamental insights into how the human system recognizes carbohydrates and drive the discovery of carbohydrate vaccines.
Highlights
Humans have been living with and fighting infectious diseases from the dawn of mankind
Infectious diseases caused by bacteria, viruses, and parasites remain a major global health problem as vividly illustrated by the COVID-19 pandemic
Five synthetic oligosaccharide antigens resembling SP2, serotype 3 (SP-3), serotype 5 (SP-5), serotype 8 (SP-8), and SP-14 were conjugated to CRM197 carrier protein to test such an approach (Figure 23)
Summary
Humans have been living with and fighting infectious diseases from the dawn of mankind. Infectious diseases caused by bacteria, viruses, and parasites remain a major global health problem as vividly illustrated by the COVID-19 pandemic. Thanks to the advent of vaccines, smallpocks and polio were almost eradicated in the 20th century Many deadly infections, such as those caused by tetanus that repeatedly resulted in death after small injuries, are almost entirely forgotten today. The need to develop effective vaccines against many different infectious diseases caused by viruses, parasites, and bacteria is more urgent today than at any time since the development of the polio vaccine.[1] With a greatly improved understanding of the human immune system and pathogen biology, the stage is set to create new vaccines to offer protection from infectious diseases that have become resistant to antibiotics. Synthetic chemistry is the enabling technology that supports the creation of efficacious and affordable vaccines
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