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A M Tenbergen-Meekes

Publications and source records attributed to A M Tenbergen-Meekes.

10 recordsLinked to original sources
PubMed1995

Immunoglobulin isotype-specific antibody responses to pneumococcal polysaccharide vaccine in patients with recurrent bacterial respiratory tract infections.

Anti-pneumococcal IgM, IgG1, IgG2, and IgA antibody titers were determined in 61 pediatric patients with recurrent bacterial respiratory tract infections. The patients were divided in those with normal serum Ig levels (group 1, n = 46) and patients with dysimmunoglobulinemia (group II, n = 15). antibody titers to five pneumococcal serotypes (3, 4, 6A, 9N, and 19F) of different immunogenicity were determined by ELISA, before and 14 d after immunization with pneumococcal polysaccharide vaccine. In the patients of group I, IgM responses did not vary between the various serotypes. IgG1 antibodies reached high levels for pneumococcal types 3, 4, and 9N compared with an adult reference hyperimmune plasma pool, but remained low for the weak immunogenic types 6A and 19F. IgG2 antibody titers remained low and were nearly absent in 20/46 patients. The fold increase in IgA was high, but the ultimate IgA antibody levels remained low. IgA levels remained low to absent in 10/46 patients. Two patients (4%) of group I failed to show antipneumococcal antibodies of all Ig isotypes. In group II, 6/15 patients (40%) made no anti-pneumococcal antibodies of any isotype, whereas the remaining patients made no IgG2 and/or IgA anti-pneumococcal antibodies. We conclude that the frequency of nonresponders to pneumococcal vaccination in patients with normal serum Ig is low (4%). However, low IgG2 anti-pneumococcal levels are found in approximately 50% of the patients. In patients with dysimmunoglobulinemia, IgA and IgG2 responses were absent in virtually all patients, whereas 40% made no anti-pneumococcal antibodies of any isotype.

Adolescent↗
PubMed1992

Induction of anti-pneumococcal cell wall polysaccharide antibodies by type 4 pneumococcal polysaccharide-protein conjugates.

We have prepared polysaccharide-protein conjugates consisting of type 4 pneumococcal capsular polysaccharide (PS4) coupled to tetanus toxoid. The PS4 preparation used contained 2.5% pneumococcal cell wall polysaccharide (CPs). During the conjugation process, in addition to PS4-protein conjugates, CPs-protein conjugates were also formed. After immunization with PS4-protein conjugates, CPs-protein conjugates that are present as a contaminant induce IgG anti-CPs antibodies in mice. Pneumococcal oligosaccharides, prepared by periodate oxidation of PS4, did not contain detectable amounts of CPs; hence, oligosaccharide-protein conjugates did not induce anti-CPs antibodies.

Animals↗
PubMed1992

Immunogenicity of a Streptococcus pneumoniae type 4 polysaccharide--protein conjugate vaccine is decreased by admixture of high doses of free saccharide.

In this study we report that the priming capacity of a Streptococcus pneumoniae type 4 polysaccharide-protein conjugate to booster immunizations with the native capsular polysaccharide is dose dependent. Furthermore, it is shown by admixture experiments that simultaneous administration of high doses of free saccharide (0.5-25 micrograms) of different chain lengths (varying from M(r) 1.6-120 kDa) decreases the anti-polysaccharide antibody response. Presence of low doses of saccharide (up to 10%), which are usually present in conjugates prepared by the carbodiimide coupling procedure, did not influence the anti-polysaccharide antibody response in adult and neonatal mice.

Animals↗
PubMed1992

In vitro activation of human T lymphocytes by Haemophilus influenzae type b capsular polysaccharides.

Polyribosilribitolphosphate (PRP), the capsular polysaccharide from Haemophilus influenzae type b, is a T-cell-independent type 2 antigen. In vitro culture of adult peripheral blood T cells with 15 micrograms/ml PRP leads to induction of interleukin-2 receptor (IL-2R) expression on up to 10% of T cells. These cells are CD4+ and carry the alpha beta T-cell receptor. PRP, at concentrations above 1-5 micrograms/ml, can also induce in vitro proliferation of both adult and neonatal T cells. We conclude that PRP acts as a human T-cell mitogen. The in vitro proliferative response as well as IL-2R expression was studied in T cells derived from adults after vaccination with native PRP, with PRP conjugated to a carrier protein, or with diphtheria toxoid. Vaccination with conjugated PRP decreased the doses of PRP required for in vitro induction of IL-2R expression and T-cell proliferation. This indicates that vaccination with PRP conjugated to a carrier protein improves the in vitro T-cell response to PRP activation.

Adult↗
PubMed1991

In vitro induction of a Haemophilus influenzae type b polysaccharide-specific antibody response in human peripheral blood lymphocytes of individuals recently vaccinated with an oligosaccharide-protein conjugate.

In this paper an in vitro culture system for the induction of an antibody response to the Haemophilus influenzae type b polysaccharide (PRP) is described. Anti-PRP IgM and IgG antibody-secreting cells (ASC) and anti-diphtheria toxoid (DT) IgG ASC were detected in cultures of blood B and T cells derived from donors 4 to 6 wk after immunization with Haemophilus influenzae type b oligosaccharide-mutant diphtheria toxin (CRM197) conjugate (HbOC) and required in vitro restimulation with HbOC. When lymphocytes from HbOC-vaccinated donors were stimulated with PRP, anti-PRP IgM and IgG ASC could be detected in 50% offGe cases. Lymphocytes from PRP-vaccinated donors or non-vaccinated donors consistently failed to generate anti-PRP antibodies after in vitro stimulation with HbOC. Optimal in vitro responses were observed at concentrations of 0.06 to 0.6 micrograms/ml of Ag. At higher doses of Ag (6 micrograms/ml) anti-PRP and anti-DT antibody responses were suppressed. The in vitro generation of anti-PRP and anti-DT ASC, as detected by a spot-forming cell assay was shown to be T cell dependent, Ag dependent, and Ag specific. This culture system provides a model for the study of human B cell activation and immunoregulation by polysaccharide-protein conjugates and polysaccharides.

Adult↗
PubMed1991

A comparative study of the immunogenicity of pneumococcal type 4 polysaccharide and oligosaccharide tetanus toxoid conjugates in adult mice.

A number of pneumococcal type 4 poly- and oligosaccharide tetanus toxoid conjugates were prepared using identical conjugation methods. Purified conjugates with similar m.w. were injected in mice; polysaccharide conjugates (PS4TT) were more immunogenic than oligosaccharide conjugates (OS4TT). Polysaccharide conjugates with a PS4:TT ratio less than 1 (w/w) appeared to be the most immunogenic conjugates. This was observed in both NIH (outbred) and BALB/c (inbred) strains of mice. Oligosaccharide tetanus toxoid conjugates required w/w ratios of greater than 1 to acquire optimal immunogenicity. Oligosaccharides (12 repeating units) of pneumococcal type 4, obtained by periodate cleavage, appeared to retain full antigenicity as measured by competition ELISA. Both PS4TT and OS4TT conjugates induced an antibody response with the characteristics of a T cell-dependent type of immune response. An anti-PS4 IgG and IgM booster effect could be demonstrated for all conjugates. The IgG subclass response induced by PS4TT and OS4TT conjugates is primarily IgG1 but IgG3 is also detectable. However, the amounts of anti-PS4 IgG3 differed for the various conjugates. We conclude that the immune response induced by pneumococcal type 4 saccharide tetanus toxoid conjugates can be manipulated by variation of the saccharide:protein ratio and the saccharide chain length, whereas keeping the m.w. of such conjugates at constant values.

Animals↗
PubMed1991

Pneumococcal conjugate vaccines.

We have prepared conjugates of pneumococcal type 4 polysaccharides (PS4) or oligosaccharides to tetanus toxoid using the carbodiimide method. The use of a spacer, 6-aminohexanoic acid, resulted in higher incorporation of carrier protein. Conjugates contained up to 10% free polysaccharide, but no free protein. In general, polysaccharide conjugates induced higher anti-PS4 IgG antibody titers than oligosaccharide conjugates. Conjugates with the highest amount of incorporated protein were the most immunogenic. The response to conjugated PS4 does show characteristics of a T cell-dependent antibody response, in terms of both isotype distribution and induction of immunological memory. Repeated immunization with high doses of PS4TT conjugate resulted in a virtually negative anti-PS4 IgG response, suggestive of the induction of high dose tolerance.

Animals↗
PubMed1991

Effect of carrier priming on immunogenicity of saccharide-protein conjugate vaccines.

Previous studies with saccharide-protein conjugates have demonstrated that antibody responses to the saccharide can be improved by the preexistence of carrier immunity. Here we report that prior exposure to the carrier protein can either enhance or suppress antibody response to polysaccharides administered in saccharide-protein conjugates. A dose-dependent role for carrier priming in the antisaccharide antibody response to three saccharide-protein conjugate vaccines, i.e., a Streptococcus pneumoniae type 4 polysaccharide-tetanus toxoid (TT) conjugate (PS4TT), a Neisseria meningitidis group C polysaccharide-TT conjugate (MenCTT), and a N. meningitidis group C oligosaccharide-diphtheria mutant toxin conjugate (MenCCRM), was investigated. The results showed that an increase in the antipolysaccharide antibody response could be obtained for both PS4TT and MenCTT but not for MenCCRM with low-dose carrier priming (0.025 to 0.25 microgram). However, suppression of the antipolysaccharide antibody response was observed with the PS4TT and MenCTT vaccines with high-dose (25-micrograms) carrier priming. There was no suppression effect with MenCCRM. The increase in the antipolysaccharide antibody response was shown to be restricted to the immunoglobulin G1 (IgG1) subclass, whereas suppression with high-dose carrier priming affected all antipolysaccharide subclass antibodies induced by PS4TT (IgG1, IgG2b, and IgG3) and only two of the four subclass antibodies induced by MenCTT (IgG2a and IgG2b). The increase in the antipolysaccharide antibody response was also present at the antipolysaccharide IgM antibody level but was not observed at the anti-carrier IgG antibody level.

Animals↗