Capsular Polysaccharide Vaccines and Protein Carriers (Conjugate Vaccines)

Haemophilus influenzae type b (HIb) and Neisseria meningitidis are the major cause of bacterial meningitis in infants, toddlers and young adults. Phagocytosis is the primary defence mechanism against extracellular pathogens. A major pathogenic feature of Haemophilus influenzae type b (HIb), Neisseria meningitidis and Streptococcus pneumoniae is the presence of hydrophilic polysaccharides which possess anti-phagocytic properties. This feature allows the pathogens to establish infection within the host. The production of opsonising antibodies of the IgG isotype that promote phagocytosis is a key process in eliminating these pathogens. This is the basis of the current vaccines.
However, polysaccharides are generally weak inducers of antibody responses due to poor T-helper cell responses to polysaccharides. This leads to poor immunological memory and diminished antibody class switching to IgG. Poor immune responses were a feature of the first polysaccharide-based vaccines. This problem has been overcome by the use of carrier proteins conjugated to the polysaccharides. Such vaccines are referred to as conjugate vaccines and are now routinely used in vaccination against Haemophilus influenzae type b (HIb) and Neisseria
meningitides. The use of carrier proteins has greatly enhanced the immunogenicity of these vaccines. The basis for this is that the carrier protein is processed by host cells and activates T-helper cells resulting in the cytokines required to produce memory and antibody isotype switching. The carrier proteins used are inactivated bacterial exotoxins (toxoids), in particular tetanus toxoid. This exploits the fact that individual will have been immunised against tetanus  and will have memory T cells to the carrier protein, in turn increasing the effectiveness of the T cell contribution.
S. pneumoniae displays considerable variability in the polysaccharide capsule. The vaccine contains up to 23 different polysaccharides from the major serovars. Alternatively, a conjugate vaccine containing major polysaccharides is available. A polysaccharide-based typhoid vaccine is also available.