Improving efficacy of glycoconjugate vaccines: from chemical conjugates to next generation constructs.

Glycoconjugate vaccines are among the safest and most successful vaccines developed during the past 30 years. Since the first semisynthetic chemical conjugate vaccine licensed in the 1980's to protect human against Haemophilus influenzae type b infection, conjugate vaccines against Neisseria meningitidis and Streptococcus pneumoniae have been developed and registered using the same approach (i.e. bacterial growth to produce capsular polysaccharide antigen and chemical coupling to carrier protein). Other types of conjugate vaccines have been recently developed and tested in clinical trials, prepared by coupling chemically synthesized oligosaccharides to proteins, by engineering Escherichia coli to directly produce bioconjugates or by delivering the native carbohydrate antigen in engineered membrane vesicles (i.e. Generalized Modules for Membrane Antigens, GMMA). Through this review, the reader will have an insight regarding the history and the characteristics of different types of conjugate vaccines, and the attributes that might affect their immunogenicity and their potential for future applications.