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.Protection against infections with encapsulated bacteria such as Streptococcus pneumoniae depends on the presence of antibodies against capsular polysaccharides. These serotypespecific antibodies facilitate phagocytosis, the main mode of host defense against S. pneumoniae. The spleen is an important organ in the immune response to S. pneumoniae, since it contains both antibody-producing B cells and phagocytes (4, 26). Asplenic patients are therefore at increased risk for invasive infections with S. pneumoniae (13). Although most infections occur within the first few years after splenectomy, the risk of overwhelming postsplenectomy infections is lifelong (9, 36). Therefore, vaccination against S. pneumoniae is indicated for this group. At present, the vaccine available for this aim is the 23-valent pneumococcal polysaccharide (PPS) vaccine (1). The immunogenicity of PPS vaccine in splenectomized patients has been assessed in a number of trials. Some studies have shown the effectiveness of vaccination in inducing protective concentrations of specific antibodies (5, 10, 24, 33), while others have shown limited serological responses (15). As the initiation of the antibody response to polysaccharides seems to depend on the presence of splenic tissue, and in particular on a functional marginal-zone B-cell compartment (3,14,18,34), it may be expected that polysaccharide vaccines are of limited use in asplenic patients.The physical coupling of a polysaccharide to a carrier protein greatly improves the immunogenicity of the polysaccharide, a principle first described in 1929 (11). Conjugated polysaccharides overcome the antipolysaccharide unresponsiveness in early life (2, 8), which is thought to be due to a still immature splenic marginal-zone B-cell compartment (2). The induction of antipolysaccharide antibodies by conjugate vaccines at a young age suggests that conjugates might initiate the antipolysaccharide anti...

Depletion of Complement Has Distinct Effects on the Primary and Secondary Antibody Responses to a Conjugate of Pneumococcal Serotype 14 Capsular Polysaccharide and a T-Cell-Dependent Protein Carrier

“…Our results also confirm reports that immunization with PPS conjugate vaccines can induce a strong antibody response in the absence of a spleen (3,54). The means by which conjugation of TD carriers to PPS bypasses the requirement for the spleen in the anti-PPS antibody response is currently unknown, but likely involves enhancement of the anti-PPS14 immune response in extrasplenic locations.…”

Immune Response to Meningococcal Serogroup C Conjugate Vaccine in Asplenic Individuals

“…The extended period between vaccination and sample collection for several individuals did not account for any of the patients who failed to achieve an SBA titer of Ն8. The importance of a functional spleen in the response to polysaccharide vaccines has previously been demonstrated (4,20). However, polysaccharide-protein conjugate vaccines have been shown to overcome dependence upon the presence of a functional spleen (4,14,30).…”

“…The importance of a functional spleen in the response to polysaccharide vaccines has previously been demonstrated (4,20). However, polysaccharide-protein conjugate vaccines have been shown to overcome dependence upon the presence of a functional spleen (4,14,30). Hib conjugate vaccines have been shown to be immunogenic in splenectomized children and adolescents (14) and in children with congenital asplenia (30).…”

Enhanced vulnerability for Streptococcus pneumoniae sepsis during asplenia is determined by the bacterial capsule

“…The spleen is especially important for IgM and IgG2 antibody responses to polysaccharide antigens, generated by B cells in the marginal zone (Breukels et al 2001). After splenectomy this antibody response is attenuated, resulting in a reduced recognition of carbohydrate neoantigens and a delayed bacterial clearance upon entry in the circulation (Altamura et al 2001).…”