Vaccination is arguably the most economical and efficacious part of preventive health care. Often life-long immunity and even eradication of the infectious agent is possible to achieve with no or very minor side-effects. Commercial glycoconjugate vaccines, constructed from a bacterial polysaccharide conjugated to a carrier protein, have proven to be most efficient against a variety of bacteria causing meningitis, Haemophilus influenzae type b, Neisseria meningitidis type A, C, Y, and W, and Streptococcus pneumoniae (up to thirteen serotypes). However, sometimes there are complications with the use of native polysaccharides in construction and development of a vaccine. Examples are problems with instability, heterogeneity, conjugation, and molecular mimicry. In these instances an attractive alternative is to use chemically synthesized glycan structures, which allows for analogues and part structures to be constructed to circumvent complications with the native polysaccharide. Conjugate vaccines based on well defined synthetic oligosaccharides further provide tools for SAR studies to define size and structures of protective carbohydrate epitopes. With access also to synthetic T-antigen peptides and (if required) adjuvants, fully synthetic vaccine candidates can be assembled and tested. Synthesis of oligosaccharide structures corresponding to Streptococcus pneumonia type 1 and 14, Cryptococcus neoformans serotype A and D, Moraxella catarrhalis, and Neisseria meningitidis capsular- and lipopolysaccharide structures will be presented as well as immunological evaluation of libraries of S. pneumonia type 14 and C. neoformans serotype A and D structures to determine protective epitopes of these polysaccharides. Furthermore, the construction and immunological testing of a fully synthetic vaccine based on S. pneumoniae type 14 structures assembled on to gold nanoparticles will be discussed.
