Antibody response and protective immunity were evaluated in mice immunized with pneumococcal
glycoconjugate vaccines using two pneumococcal
protein carriers. Mice injected with type 9V
polysaccharide (PS) conjugated to inactivated
pneumolysin (Ply) or
autolysin (Aly) produced high levels of
IgG and
IgM antibodies to both the PS and the
protein carrier. Higher PS antibody titers to the pneumococcal PS conjugates were measured by ELISA using PS-Ply or PS-
tetanus toxoid (TT) conjugate as a coating
antigen compared with PS mixed with methylated
human serum albumin. Type 9V PS (10 microg) inhibited most of the 9V
IgM and
IgG antibody binding to the 9V-TT coated plate. In contrast, absorption with 19F PS did not inhibit 9V antibody binding. The avidity index of
IgG antibodies in the 9V PS-Ply serum was 55.5 +/- 0.9, compared with 47.8 +/- 1.4 for 9V PS-Aly serum. Thus, high avidity of serum
antibodies in conjugate-immunized mice can provide more effective functional activity for protection against
pneumococcal infection. Mice immunized with these
glycoconjugates exhibited rapid bacterial clearance from blood and provided cross-protection against challenge with heterologous serotypes of virulent pneumococci. These results reveal that conjugates using pneumococcal
protein carriers can induce opsonophagocytic activity to destroy homologous and heterologous pneumococci, indicating that such conjugates can confer broader protective immunity than conjugates using non-pneumococcal
proteins.