RECENT DEVELOPMENTS IN BACTERIAL CONJUGATE VACCINES

Study of the epidemiology of childhood infection reveals that the brun t of disease for a number of invasive bacterial infections is borne by children under the age of 4 years. Haemophilus influenzae type b (Hib ), Neisseria meningitidis and Streptococcus pneumoniae, the three most important causes of childhood meningitis, illustrate this phenomenon, which is caused by the inability of infants and young children to mou nt antibodies to the carbohydrates that form a capsule surrounding the se organisms. Carbohydrates are traditionally viewed as T-independent antigens with a number of unique and important immunological propertie s that are not encountered when inducing an immune response to protein s. These properties include no overt requirement for the presence of T cells to induce an immune response, dominance of IgM, failure to indu ce memory following immunisation, an absence of affinity maturation fo llowing immunisation, and poor immunogenicity in infants, the elderly and the immunocompromised. These properties of carbohydrates have prec luded the use of pure carbohydrate vaccines in those patients most at risk. Conjugate vaccine technology, where a carbohydrate antigen is co upled chemically to a protein carrier, has overcome the limitations of carbohydrates as vaccine antigens by rendering the carbohydrate moiet y of such vaccines immunogenic, even in the very young. The dramatic s uccess of the Hib conjugate vaccines, the first conjugates licensed cl inically for human use, in reducing the incidence of invasive Hib dise ase has demonstrated the potential value of such conjugate vaccines. S imilar technology is, therefore, being applied to a number of other va ccines in development, including N. meningitidis (groups A and C) and S. pneumoniae vaccines. The large number of pneumococcal carbohydrate serotypes that require inclusion in a vaccine makes this conjugate for mulation far more complicated than that for Hib, and it is likely that the dramatic success of the Hib conjugate vaccines will be more diffi cult to repeat for the pneumococcus.