The design of semi-synthetic and synthetic glycoconjugate vaccines.
BACKGROUND
Glycoconjugate vaccines are among the safest and most efficacious vaccines developed during the last 30 years. They are a potent tool for prevention of life-threatening bacterial infectious diseases like meningitis and pneumonia. The concept of hapten-carrier conjugation is now being extended to other disease areas.


METHODS
This is an overview of the history and current status of glycoconjugate vaccines. The authors discuss the approaches for their preparation and quality control as well as those variables which might affect their product profile. The authors also look at the potential to develop fully synthetic conjugate vaccines based on the progress of organic chemistry. Additionally, new applications of conjugate vaccines technology in the field of non-infectious diseases are discussed. Through this review, the reader will have an insight regarding the issues and complexities involved in the preparation and characterization of conjugate vaccines, the variables that might affect their immunogenicity and the potential for future applications.


CONCLUSIONS
The immunogenicity of weak T-independent antigens can be increased in quantity and quality by conjugation to protein carriers, which provide T-cell help. Glycoconjugate vaccines are among the safest and most efficacious vaccines developed so far. Various conjugation procedures and carrier proteins can be used. Many variables impact on the immunogenicity of conjugate vaccines and a tight control through physicochemical tests is important to ensure manufacturing and clinical consistency. New and challenging targets for conjugate vaccines are represented by cancer and other non-infectious diseases.
Novartis Vaccines, Via Fiorentina 1, Siena 53100 ,  Italy   rino.rappuoli@novartis.com.
Paolo
P
Costantino
Rino
R
Rappuoli
Francesco
F
Berti