Carbohydrate-Based Vaccines

Julia Hütter, Bernd Lepenies, Hütter, Julia, Lepenies, Bernd

Vaccination is one of the key developments in the fight against infectious diseases. It is based on the principle that immunization with pathogen-derived antigens provides protection from the respective infection by inducing an antigen-specific immune response. The discovery by Avery and Heidelberger in the 1920s that capsular polysaccharides (CPS) from Streptococcus pneumoniae are immunoreactive was the starting point of the development of carbohydrate-based vaccines. CPS-specific neutralizing antibodies were found to mediate protection against S. pneumoniae infection. Since the majority of bacterial pathogens carry a dense array of polysaccharides on their surface, the carbohydrate-based vaccine approach was applied to a variety of bacterial strains. The first CPS-based vaccines against S. pneumoniae were licensed in the 1940s. The increasing emergence of antibiotic-resistant bacterial strains since the 1960s boosted the development of carbohydrate-based vaccines and led to the approval of CPS-based vaccines against Neisseria meningitidis, Haemophilus influenzae type b (Hib), and Salmonella typhi. Meanwhile, it was observed that CPS generally do not elicit protective antibody responses in children below the age of 2 years who are at the greatest risk of infection. As a consequence, studies refocused on the conjugation of oligosaccharides to proteins in order to increase vaccine immunogenicity which led to the introduction of the first glycoconjugate vaccine against Hib in 1987. Due to the success of the first glycoconjugate vaccines, higher valent formulations were developed against numerous bacterial infections to achieve broad serotype coverage. Current research also focuses on the development of carbohydrate-based vaccines against other pathogens such as viruses, fungi, protozoan parasites, or helminths.