Synthesis of a conjugate vaccine composed of pneumococcus type 14 capsular polysaccharide bound to pertussis toxin

Schneerson, Rachel; Levi, Lily; Robbins, John B.; Bryla, Dolores A.; Schiffman, Gerald; Lagergård, Teresa

doi:10.1128/iai.60.9.3528-3532.1992

Cited by 32 publications

(6 citation statements)

References 36 publications

(70 reference statements)

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“…This IgG subclass imbalance with defective PS Ag response might be explained by a delayed development of B cell maturation, suggestive of transient hypogammaglobulinemia. Schneerson et al 27 have recently proposed the enhanced effect of a conjugate vaccine of pneumococcal PS bound to PT on the specific Ab response to PS. The combined vaccination of DPT and pneumovax might be advantageous for the patients with IgG subclass deficiency.…”

Section: Discussionmentioning

confidence: 99%

Recurrent pneumococcal meningitis in a patient with transient IgG subclass deficiency

Ohga

Okada

Asahi

et al. 1995

Pediatrics International

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We report the case of a 3 year old boy who exhibited recurrent serious infections with a transient imbalance of IgG subclass in the second year of life. He suffered from pneumococcal meningitis at 3 months, hepatitis at 9 months, and purulent arthritis at 11 months of age. The second episode of pneumococcal meningitis occurred at 14 months. Serum IgG level was normal for age. Low level of IgG2, undetectable level of IgG4 and negligible level of pneumococcus‐specific IgG1‐G2 antibodies were found. No other primary immunodeficiency was apparent. Serum IgG2‐G4 levels but not pneumococcus‐specific IgG1‐G2 titers increased by the age of 30 months. At that time, he was inoculated with a polyvalent pneumococcal vaccine along with acellular diphtheria‐pertussis‐tetanus vaccine. He acquired the immunity against these agents, and had no episodic infections in the following 2 years. This observation stresses the existence of transient IgG subclass deficiency associated with delayed development of the anti‐polysaccharide antibody response.

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Section: Discussionmentioning

confidence: 99%

Recurrent pneumococcal meningitis in a patient with transient IgG subclass deficiency

Ohga

Okada

Asahi

et al. 1995

Pediatrics International

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“…In accordance with this observation, preliminary studies showed that the vaccine responses of the aged mice can be enhanced by supplementation with IL-10, a cytokine that can antagonize IFN-␥ production (29a, 34). Also, strategies to make the vaccine T-cell dependent may not be as important for older individuals (6,38,44), since the necessary T-cell-derived cytokine, IL-5, is already high in aged mice but is unable to help the vaccine response. In summary, these studies showed for the first time that the hyporesponsiveness of older animals to pneumococcal PS vaccine is due to an accessory cell deficiency and have suggested strategies to increase the vaccine efficacy for this population.…”

Section: Downloaded Frommentioning

confidence: 99%

Cellular basis of decreased immune responses to pneumococcal vaccines in aged mice

et al. 1996

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Previously, model systems were developed in our laboratory to study murine immune responses to the 23-valent pneumococcal polysaccharide vaccine Pnu-Imune, both in vivo and in vitro (M. Garg and B. Subbarao, Infect. Immun. 60:2329-2336, 1992; M. Garg, A. M. Kaplan, and S. Bondada, J. Immunol. 152: [1589][1590][1591][1592][1593][1594][1595][1596] 1994). Using these systems, we found that aged mice did not respond to the vaccine in vivo or in vitro. Cell separation studies showed that the unresponsiveness of the aged spleen cells to the vaccine was not due to an intrinsic B-cell defect or to T-cell-mediated immunosuppression but resulted from an accessory cell deficiency. Irradiated spleen cells from young mice enabled the old mouse spleen cells to respond to the vaccine. Interestingly, irradiated spleen cells from old mice also restored the vaccine responsiveness in old mice but were required in greater numbers than the young mouse spleen cells to induce similar levels of response. The accessory cell was an adherent cell that could be removed by passage through Sephadex G-10 and thus may be a macrophage. Accessory function could also be provided by the cytokine interleukin-1 (IL-1), IL-4, or IL-5 but not IL-2 or IL-6. Thus, one reason for the deficient immune response to pneumococcal vaccine in aged mice is a quantitative defect in adherent accessory cells.

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“…CPS expression for naturally occurring phase variants of V. vulnificus, as well as for genetically defined mutants, was evaluated by ELISA, IEM, or FC analyses with a CPS-specific monoclonal antibody. Difficulties in obtaining monoclonal or polyclonal antibodies to purified capsule preparations have been reported (29), but increased antibody responses can be achieved by the use of protein carriers (6). Previously described tetanus toxoid conjugates to purified V. vulnificus CPS elicit the greatest polyclonal response in mice (10) and were used to produce monoclonal antibodies in mice.…”

Section: Discussionmentioning

confidence: 99%

Differential Expression ofVibrio vulnificusCapsular Polysaccharide

et al. 1999

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Vibrio vulnificus is a human pathogen whose virulence has been associated with the expression of capsular polysaccharide (CPS). Multiple CPS types have been described; however, virulence does not appear to correlate with a particular CPS composition. Reversible-phase variation for opaque and translucent colony morphologies is characterized by changes in CPS expression, as suggested by electron microscopy of cells stained nonspecifically with ruthenium red. Isolates with opaque colony morphologies are virulent and appear to be more thickly encapsulated than naturally occurring translucent-phase variants, which have reduced, patchy, or absent CPS. Previously, we have shown that the virulence of translucent-phase variants was intermediate between opaque-phase variants and acapsular transposon mutants, suggesting a correlation between virulence and the amount of CPS expressed. In the present study, CPS expression of phase variants and genetically defined mutants of V. vulnificusM06-24/O was examined by using a CPS-specific monoclonal antibody with an enzyme-linked immunosorbent assay, flow cytometry, and immunoelectron microscopy. Semiquantitative analyses of CPS expression correlated well among these assays, confirming that the translucent-phase variant was intermediate in CPS expression and retained type I CPS-specific epitopes. Cell surface expression of CPS varied with the growth phase, increasing during logarithmic growth and declining in stationary culture. Significantly greater CPS expression (P = 0.026) was observed for cells grown at 30°C than for those at 37°C. These studies confirm that phase variation and virulence in V. vulnificus correlate with the amount of CPS expressed and demonstrate the fluidity of bacterial polysaccharide expression in response to environmental conditions.

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Synthesis of a conjugate vaccine composed of pneumococcus type 14 capsular polysaccharide bound to pertussis toxin

Cited by 32 publications

References 36 publications

Recurrent pneumococcal meningitis in a patient with transient IgG subclass deficiency

Recurrent pneumococcal meningitis in a patient with transient IgG subclass deficiency

Cellular basis of decreased immune responses to pneumococcal vaccines in aged mice

Differential Expression ofVibrio vulnificusCapsular Polysaccharide

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