Serum anticapsular polysaccharide antibodies confer immunity to invasive diseases

Serum anticapsular polysaccharide antibodies confer immunity to invasive diseases caused by Haemophdus influenzae type b (HIB) t (1-10). These anti-type b antibodies exert their protective effect by initiating complement-mediated activities including opsonization and bacterial lysis (2-5, 11). A protective level of ~0.15 #g of anti-type b antibodies/ml serum was estimated based upon analyses of patients with X-linked hypogammaglobulinemia who were passively immunized with immunoglobulin and on analyses of vaccinees injected with the purified HIB capsular polysaccharide (HIB Ps) (6-8, 11-13). In two field trials the HIB Ps induced a protective immune response only in children older than 18-24 mo (6-8). Reinjection of the HIB Ps did not induce a booster effect at any age (8, 13, 14). This age-related immunological behavior to HIB Ps in humans is similar to that observed with other purified bacterial capsular polysaccharides (14-17) and has been characterized as "thymic-independent" (12, 18, 19). To achieve immunoprophylactic control of meningitis caused by HIB and other encapsulated bacteria, a more effective vaccine for infants, perhaps with "thymicdependent" properties, must be developed. Goebel (20) and Avery and Goebel (21, 22) prepared protein conjugates of the pneumococcus type 3 polysaccharide as well as of its repeating dissacharide unit, cellobiuronic acid. In contrast to the poor immunogenicity of the purified type 3 polysaccharide in rabbits, these protein-carbohydrate conjugates induced high levels of serum antibodies that increased in concentration with reinjection and were protective against challenge with the live organisms (23, 24). Other investigators, using carbohydrates derived from pathogenic bacteria, have prepared covalently bound conjugates with proteins, noncovalently bound protein-polysaccharide complexes, or polysaccharide-erythrocyte conjugates. These products revealed enhanced immunogenicity of the carbohydrate moiety (25-36). In some cases, the conjugate-induced anti-carbohydrate antibodies were shown to have a protective effect against the bacteria from which they were derived. Many investigators injected these conjugates