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David Goldblatt

Publications and source records attributed to David Goldblatt.

At least 19 recordsLinked to original sources
PubMed2006

Clinical and immunologic risk factors for meningococcal C conjugate vaccine failure in the United Kingdom.

BACKGROUND: The meningococcal serogroup C conjugate (MCC) vaccine was introduced into the United Kingdom with licensure based on immunogenicity data not efficacy data. METHODS: All subjects with laboratory-confirmed meningococcal serogroup C (MenC) disease from January 2000 to December 2003 in England and Wales were followed up. A vaccine failure was defined as a laboratory-confirmed case of MenC disease occurring > or =10 days after the subject's last scheduled dose of MCC vaccine. Total immunoglobulins, serum bactericidal antibody (SBA) titers, MCC anticapsular antibody levels, and avidity indices (AIs) were measured in acute and convalescent serum samples from subjects with vaccine failure and unvaccinated subjects with MenC disease. RESULTS: Of 465 subjects with confirmed MenC disease identified among those eligible for vaccination, information on vaccination history was obtained for 462 (99.4%); of these, 53 were subjects with vaccine failure. SBA titers in convalescent serum samples and AIs in acute serum samples were significantly higher in subjects with vaccine failure than in unvaccinated subjects, (6.1-fold higher for SBA titers [P=.03] and 3.2-fold higher for AIs [P=.001]). CONCLUSIONS: The antibody response in the subjects with vaccine failure was consistent with an anamnestic response, suggesting that MenC disease occurred despite the MCC vaccine priming for immune memory. Persistence of antibodies may be a more appropriate correlate of long-term protection for MCC vaccines than the ability to generate a booster response on exposure.

Adolescent↗
PubMed2006

Lack of association between the nasopharyngeal carriage of Streptococcus pneumoniae and Staphylococcus aureus in HIV-1-infected South African children.

We investigated the nasopharyngeal carriage of Streptococcus pneumoniae and Staphylococcus aureus in 355 children hospitalized with severe pneumonia. Of the children, 239 (67.3%) were human immunodeficiency virus (HIV)-1 positive; 169 (47.6%) carried S. pneumoniae, 91 (25.6%) carried S. aureus, and 33 (9.3%) carried both. S. pneumoniae carriage was not related to HIV-1 status. The HIV-1-positive children had a significantly higher rate of S. aureus carriage than did the HIV-1-negative children (31.4% vs. 13.8%; P<.001). The rate of S. aureus carriage in the HIV-1-negative S. pneumoniae carriers was significantly lower than that in the noncarriers (5.5% vs. 21.3%; P=.013), but the rate of S. aureus carriage in the HIV-1-positive S. pneumoniae carriers was not significantly lower than that in the noncarriers (26.3% vs. 36.0%; P=.11). We did not find a negative association between S. pneumoniae and S. aureus carriage in HIV-1-positive hospitalized children with severe pneumonia.

Child, Preschool↗
PubMed2006

Immunogenicity and boosting after a reduced number of doses of a pneumococcal conjugate vaccine in infants and toddlers.

BACKGROUND: The minimum number of doses of pneumococcal conjugate vaccine required for protection is not known. We studied the immunogenicity of a reduced schedule in infants and toddlers. METHODS: U.K. infants were given either 2 or 3 doses (at 2 and 4 or 2/3/4 months of age) of a 9-valent pneumococcal conjugate vaccine (9VPCV) followed by boosting at 12 months of age. In a separate study, toddlers (12 months) received 1 or 2 doses (2 months apart) of 9VPCV followed by pneumococcal polysaccharide vaccine at 18 months of age. RESULTS: For infants, serotype-specific IgG geometric mean concentrations were similar post-primary immunization between the groups with both showing avidity maturation and similar booster responses. For toddlers, the primary response to 4 of the 9 serotypes was lower in the 1- compared with the 2-dose group (type 6B, 0.77 versus 7.1; type 14, 4.67 versus 14.98; type 19F, 5.05 versus 7.75; type 23F, 2.48 versus 5.05), although for all serotypes booster responses were similar between groups, and the postprimary responses in the 1-dose group were at least as high as those after infant immunization. CONCLUSIONS: The 2-dose infant priming schedule of 9VPCV is comparable with the 3-dose schedule and may thus be equally protective, whereas 1 dose in toddlers may suffice for a catch-up.

Antibodies, Bacterial↗
PubMed2006

Effect of month of vaccine administration on antibody responses in The Gambia and Pakistan.

OBJECTIVE: To explore the relationship between calendar month of administration and antibody (Ab) response to vaccination in subjects from The Gambia and Pakistan, two countries with distinct patterns of seasonality. METHODS: Three cohorts were investigated: Responses to rabies and pneumococcal vaccine were assessed in 472 children (mean age 8 years, males 53%) from rural Gambia. Responses to tetanus, diphtheria and hepatitis B (HBsAg) were investigated in 138 infants also from The Gambia (birth to 52 weeks of age, males 54%). Responses to rabies and Vi typhoid vaccines were assessed in 257 adults from Lahore, Pakistan (mean age 29.4 years, males 57%). RESULTS: In Gambian children, significant associations were observed between month of vaccination and Ab response for the pneumococcal and rabies vaccines. As no consistent pattern by month was observed between the responses, it is assumed that different immunomodulatory stimuli or mechanisms were involved. In Pakistani adults, a significant pattern by month of vaccination was observed with both rabies and typhoid vaccine. No monthly influences were observed in the infant study to the tetanus, diphtheria or the HbsAg vaccines. CONCLUSIONS: Antibody responses to certain specific vaccines are influenced by month of administration. Further research is required to elucidate the precise mechanisms explaining these observations, but a co-stimulatory effect of seasonally variable environmental antigens is a likely cause. Future studies of Ab response to vaccination in countries with a seasonally dependent environment should consider month of vaccination when interpreting study findings.

Adult↗
PubMed2006

Critical differences between pneumococcal polysaccharide enzyme-linked immunosorbent assays with and without 22F inhibition at low antibody concentrations in pediatric sera.

A comparative study was conducted between two laboratories in order to evaluate the differences between two enzyme-linked immunosorbent assay (ELISA) techniques for the detection of pneumococcal anti-capsular polysaccharide antibodies. One laboratory used an assay including heterologous 22F polysaccharide inhibition, and the other laboratory employed a non-22F reference assay. After conjugate immunization, 30 pediatric post-primary immunization sera with antipolysaccharide concentrations ranging from <0.05 to 15 mug/ml were analyzed. Aggregate reverse cumulative distribution curves combining concentrations of antibodies against serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F revealed similar results for both methods at antibody levels of >1 microg/ml. However, at antibody levels of <1 microg/ml, the distribution curve measured with the 22F inhibition ELISA shifted toward lower levels. This observation suggests that the 22F inhibition assay is more specific at low antibody concentrations, which was confirmed by heterologous polysaccharide inhibition experiments. Translation of low antibody levels suggested that the proposed threshold concentration of 0.35 mug/ml determined with the non-22F ELISA corresponded to a concentration of 0.20 mug/ml with the 22F inhibition ELISA. Pneumococcal antipolysaccharide ELISA including 22F inhibition can be recommended as a reference method.

Adult↗
PubMed2006

Pneumococcal polysaccharides interact with human dendritic cells.

Dendritic cells (DCs) are critical antigen presentation cells whose influence on murine immune responses to polysaccharide antigens has only recently been elucidated. Little is known about human DC-polysaccharide interactions. We set out to study the interaction between human monocyte-derived DCs and pneumococcal capsular polysaccharides (PPS) in vitro. Immature DCs were generated from peripheral blood monocytes and incubated with fluorescein isothiocyanate-labeled PPS type 9N or 14 for assessment of uptake. DCs were exposed to PPS type 1, 6B, 9N, 14, 19F, or 23F in the absence or presence of Escherichia coli lipopolysaccharide (LPS) for assessment of phenotypic DC maturation and cytokine production. PPS were taken up by immature DCs and proceeded to HLA-DR+ and lysosome-associated membrane protein-1+ late endosomal compartments. Uptake was reduced in the presence of cytochalasin D and wortmannin, suggesting that both cytoskeletal rearrangements and phosphatidylinositol 3-kinase activation may be required for internalization. None of the PPS tested induced DC phenotype changes, maturation, or interleukin-12 (IL-12)/IL-10 production. However, PPS were capable of modulating the response of the DCs to a second signal such as LPS. Exposure of DCs to PPS in the presence of LPS resulted in an altered cytokine balance with significantly increased IL-10 production and reduced IL-12 production compared to LPS alone. This effect was not seen using the control antigen tetanus toxoid. DC-pneumococcus interaction may affect subsequent immune responses to pneumococci, as an altered cytokine balance may have a profound effect on DC-driven T-cell priming.

Dendritic Cells↗
PubMed2005

Antibody responses to nasopharyngeal carriage of Streptococcus pneumoniae in adults: a longitudinal household study.

BACKGROUND: Natural immunity to Streptococcus pneumoniae is thought to be induced by exposure to S. pneumoniae or cross-reactive antigens. No longitudinal studies of carriage of and immune responses to S. pneumoniae have been conducted using sophisticated immunological laboratory techniques. METHODS: We enrolled 121 families with young children into this study. Nasopharyngeal (NP) swabs were collected monthly for 10 months from all family members and were cultured in a standard fashion. Cultured S. pneumoniae isolates were serotyped. At the beginning (month 0) and end (month 10) of the study, venous blood was collected from family members >18 years old. Serotype-specific antipolysaccharide immunoglobulin G (IgG) and functional antibody and antibodies to pneumolysin, pneumococcal surface protein A (PspA), and pneumococcal surface antigen A (PsaA) were measured in paired serum samples. RESULTS: Levels of anticapsular IgG increased significantly after carriage of serotypes 9V, 14, 18C, 19F, and 23F by an individual or family member. For serotype 14, a higher level of anticapsular IgG at the beginning of the study was associated with reduced odds of carriage (P = .006). There was a small (approximately 20%) but significant increase in titers of antibodies to PsaA and pneumolysin but no change in titers of antibody to PspA. CONCLUSIONS: Adults respond to NP carriage by mounting anticapsular and weak antiprotein antibody responses, and naturally induced anticapsular IgG can prevent carriage.

Adult↗
PubMed2005

Light of my life.

Explore the source record for details and available documents.

Education, Medical↗
PubMed2004

Effects of prior polysaccharide vaccination on magnitude, duration, and quality of immune responses to and safety profile of a meningococcal serogroup C tetanus toxoid conjugate vaccination in adults.

Extensive use of meningococcal AC polysaccharide (MACP) vaccines has raised concerns about induction of immunologic hyporesponsiveness to C polysaccharide. We investigated the immunogenicity and safety of a meningococcal C-tetanus conjugate (MCC-TT) vaccine in naive adults and prior MACP vaccinees. Laboratory staff (n = 113) were recruited; 73 were naive to meningococcal vaccination, and 40 had previously received > or =1 dose of MACP vaccine. Blood was taken prior to MCC-TT vaccination and 1 week, 1 month, and 6 months later. At each time point, proportions of subjects with serum bactericidal antibody (SBA) titers of > or =8 or > or =128 were similar (P > 0.46); >94% of subjects achieved titers of > or =128 at 1 month. However, the geometric mean titer (GMT) of SBA at 1 month was higher in the naive (1,757; 95% confidence interval [95% CI], 1,102 to 2,803) than in the previously vaccinated (662; 95% CI, 363 to 1,207) group (P = 0.02), and similarly at 6 months (P < 0.001). Conversely, geometric mean concentrations (GMCs) of serogroup C-specific immunoglobulin G (IgG) were significantly higher in the previously vaccinated group pre-MCC-TT and at 1 week; the groups were similar at 1 month, and there was some evidence that the GMC for the previously vaccinated group was higher at 6 months. Qualitative differences in antibodies between groups were demonstrated by using the SBA/IgG ratio, though avidity measures were similar for the two groups throughout the study. MCC-TT was well tolerated, with similar safety profiles in the two groups. Pain in the arm and headache were the most frequently reported events following vaccination. The study shows that MCC-TT is safe and immunogenic in naive and previously MACP-vaccinated adults, though the magnitude and persistence of postvaccination SBA responses in the latter group were lower.

Adult↗