Carbohydrates and Immunology: Synthetic Oligosaccharide Antigens for Vaccine Formulation

Despite the enormous progress achieved by modern medicine, numerous diseases still have a profound impact on public health. Infectious diseases caused by a variety of microorganisms (viruses, fungi and parasites) and bacteria are a global major concern and, because of the emergence, for instance, of multidrug resistance, not only in developing countries. The development of preventative therapies, such as the rational design of novel and more efficient vaccines, might offer a solution to this state of affairs and other associated drawbacks. Vaccination is considered by the World Health Organization to be the most cost-effective strategy for controlling infectious disease, because it should confer long-term protective immunity in the population. A second consideration involves cancer. The outstanding progress achieved in the identification and structural characterization of tumour-associated antigens has prompted their employment in tumour immunotherapy, on the basis of the observation that tumour cells possess specific antigens that can be recognized by an immune system appropriately conditioned to the task. Carbohydrates play key roles in many molecular recognition phenomena and they can affect any kind of interaction with the immune system. Saccharide-based antigens (bacterial capsular polysaccharides or tumour-associated carbohydrate antigens, for instance) have therefore been studied and employed in the formulation of vaccines. In recent years there has been increasing use of synthetic saccharide antigens for the formulation of vaccine candidates. These structures are indeed chemically well defined, devoid of biologic contaminants and, in principle, available in large amounts, relative to materials extracted from natural sources. In addition, synthetic saccharide antigens can also serve as haptens in protein conjugates, eliciting highly specific antibodies in animal models and humans. The great potential of synthetic saccharide antigens is attested to by the spectacular success of the Cuban vaccine against Haemophilus influenzae type b. Here we review the major advances in the development of synthetic carbohydrate-based vaccines targeted against infectious diseases and cancer.