Pneumococcal conjugate vaccines overcome splenic dependency of antibody response to pneumococcal polysaccharides

Abstract

Protection against infections with Streptococcus pneumoniae depends on the presence of antibodies against capsular polysaccharides that facilitate phagocytosis. Asplenic patients are at increased risk for pneumococcal infections, since both phagocytosis and the initiation of the antibody response to polysaccharides take place in the spleen. Therefore, vaccination with pneumococcal polysaccharide vaccines is recommended prior to splenectomy, which, as in the case of trauma, is not always feasible. We show that in rats, vaccination with a pneumococcal conjugate vaccine can induce good antibody responses even after splenectomy, particularly after a second dose. The spleen remains necessary for a fast, primary response to (blood-borne) polysaccharides, even when they are presented in a conjugated form. Coadministration of a conjugate vaccine with additional nonconjugated polysaccharides of other serotypes did not improve the response to the nonconjugated polysaccharides. We conclude that pneumococcal conjugate vaccines can be of value in protecting asplenic or hyposplenic patients against pneumococcal infections.

FIG. 1

IgG responses to vaccination with PPSs (left panels) and PPS-protein conjugates (right panels) in control and splenectomized rats. Control rats (filled symbols) and splenectomized rats (open symbols) were vaccinated i.v. and s.c. at days 0 and 28 either with 2.5 μg of each of PPS serotypes 4, 6B, 9V, 14, 19F, and 23F or with a tetravalent, PCV consisting of polysaccharides of pneumococcal serotypes 6B, 14, 19F, and 23F conjugated to tetanus toxoid. Left panels show IgG responses at days 0, 5, 28, 33, and 56 after vaccination with PPS. Antibody responses to serotypes 4 and 9V are not shown but displayed a course similar to that for serotype 6B. Right panels show IgG responses at days 0, 5, 28, 33, and 56 after vaccination with PCV. Antibody titers are expressed in units per milliliter. Shown are geometric mean antibody titers and standard errors of the means.

FIG. 2

Antipneumococcal IgG response after s.c. vaccination (left panels) compared with that of combined s.c. and i.v. vaccination with PCV (right panels). Control rats (filled symbols) and splenectomized rats (open symbols) were vaccinated s.c. (broken lines) or i.v. as well as s.c. (solid lines) at days 0 and 28 with PCV. See Fig. 1 legend for further details.

FIG. 3

Antibody response to serotype 4 and 9V polysaccharides mixed with native or conjugated polysaccharides. Control rats (filled symbols) and splenectomized rats (open symbols) were i.v. and s.c. vaccinated on days 0 and 28 with 2.5 μg of the PPS serotypes 4 and 9V mixed with conjugated (broken lines) or native (solid lines) polysaccharides of serotypes 6B, 14, 19F, and 23F. See Fig. 1 legend for further details.