Characteristics of Immune Responses to Native and Protein Conjugated Pneumococcal Polysaccharide Type 14

Dobbelsteen, Germie P. J. M. van den; Kroes, Hilde; Rees, E. P. Van

doi:10.1111/j.1365-3083.1995.tb03564.x

Cited by 9 publications

(6 citation statements)

References 41 publications

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“…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.…”

Section: Discussionsupporting

confidence: 79%

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

Test¹,

Mitsuyoshi²,

Hu³

2005

Infect Immun

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Complement activation plays a critical role in the immune response to T-cell-dependent and T-cell-independent antigens. However, the effect of conjugation of T-cell-dependent protein carriers to T-cell-independent type 2 antigens on the requirement for complement in the humoral immune response to such antigens remains unknown. We studied the role of complement activation on the antibody response of BALB/c mice immunized with the T-cell-independent type 2 antigen serotype 14 pneumococcal capsular polysaccharide (PPS14), either in unmodified form or conjugated to ovalbumin (OVA). In mice immunized with either PPS14 or PPS14-OVA, depletion of endogenous complement at the time of primary immunization by treatment with cobra venom factor (CVF) diminished serum anti-PPS14 concentrations after primary immunization but enhanced antibody responses after secondary immunization. The secondary immunoglobulin G (IgG) anti-PPS14 antibody response after immunization with PPS14-OVA was especially enhanced by complement depletion, was observed at doses as low as 0.2 g of antigen, and was maximal when CVF was administered within 2 days of immunization. The avidity and opsonophagocytic functions of IgG anti-PPS14 antibodies were comparable in mice immunized with PPS14-OVA with or without complement depletion. Serum anti-PPS14 antibody concentrations were near normal, and the enhancing effects of CVF treatment on the secondary anti-PPS14 antibody response were also apparent in splenectomized mice immunized with PPS14-OVA. These results demonstrate that complement activation can have distinct effects on the primary and secondary antibody responses to a T-cell-independent type 2 antigen, either unmodified or conjugated to a T-cell-dependent protein carrier. These differences should be taken into consideration when using complement to modulate the immune response to vaccines.

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Section: Discussionsupporting

confidence: 79%

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

Test¹,

Mitsuyoshi²,

Hu³

2005

Infect Immun

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“…Asplenic or hyposplenic patients might benefit from vaccination with PCV because polysaccharide-protein conjugates can initiate an antibody response to the polysaccharide without the need for a functional spleen (19,35,37). We therefore tested the immunogenicity of PCV in splenectomized rats and showed that a series of two doses of PCV given 6 weeks after splenectomy resulted in antibody titers that were at least as high as in control rats but that the antibody response to PPS was impaired by splenectomy (Fig.…”

Section: Discussionmentioning

confidence: 99%

Pneumococcal Conjugate Vaccines Overcome Splenic Dependency of Antibody Response to Pneumococcal Polysaccharides

Breukels

Zandvoort²,

Dobbelsteen

et al. 2001

Infect Immun

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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...

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“…This induces helper T cells to stimulate PS-specific B cells that have taken up the conjugate molecules. These B cells then produce specific antibodies and mature into memory cells (51,52).…”

Section: B Streptococcus Pneumoniaementioning

confidence: 99%

Bacterial Polysaccharides as Vaccines — Immunity and Chemical Characterization

Lee

et al. 2001

The Molecular Immunology of Complex Carbohydrates —2

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Studies on protective inununity and biochemical characterization of bacterial capsular polysaccharides (PSs) have led to many significant contributions to understanding the mechanisms of infectious diseases, host defense, and development of effective vaccines. The discovery of a specific soluble substance produced by pneumococci as a carbohydrate, provided evidence regarding the specificity of PS antigens for antibody production. It was the first non-protein antigen found to induce antibody response in humans (1). The molecular basis of inununogenicity to many PS antigens has been elucidated. Antibody responses to PS immunogens can be greatly affected by their physical and chemical properties including molecular size, specific determinants, and conformation (2).Encapsulated bacterial pathogens still cause most prevalent and serious bacterial infections in the United States and many other areas of the world. The mortality and morbidity of bacteremia, meningitis, and pneumonia caused by these organisms are particularly high in children, the elderly, and immunodeficient patients (3-7). Several factors, including the high mortality and morbidity, endemic and epidemic diseases, and expanding incidence of antibiotic-resistance strains have emphasized the importance of vaccine development for prevention of bacterial infections.The development of bacterial PS vaccines has demonstrated the full cycle of scientific discovery from laboratory on chemical structure of virulence factors to the clinical diagnosis, treatment, and eventual prevention of infectious diseases. During each stage, significant knowledge has brought forth further understanding on basic biology of bacterial infections, and importance ofinununization with PS vaccines for control of infectious diseases.

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Characteristics of Immune Responses to Native and Protein Conjugated Pneumococcal Polysaccharide Type 14

Cited by 9 publications

References 41 publications

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

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

Pneumococcal Conjugate Vaccines Overcome Splenic Dependency of Antibody Response to Pneumococcal Polysaccharides

Bacterial Polysaccharides as Vaccines — Immunity and Chemical Characterization

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