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Biomedical subjects

G R Siber

Publications and source records attributed to G R Siber.

At least 91 records · Page 5Linked to original sources
PubMed1993

Antibody response of Navajo children primed with PRP-OMP vaccine to booster doses of PRP-OMP vs. HbOC vaccine.

We compared in 12- to 15-month-old American Indian infants the safety and immunogenicity of two licensed Haemophilus influenzae type b (Hib) conjugate vaccines, PRP-OMP (PedvaxHib) and HbOC (HibTITER), administered as booster vaccinations. All infants previously received PRP-OMP for their primary Hib vaccinations at 2 and 4 months of age. The geometric mean Hib antibody concentrations (microgram/ml) measured by radioactive antigen-binding assay for those receiving PRP-OMP (n = 17) or HbOC (n = 18) were 0.593 and 0.449, respectively, before boosting (P not significant) and 7.46 and 29.5 micrograms/ml, respectively, after boosting (P < 0.05). PRP-OMP recipients also had lower geometric mean IgG anti-Hib antibody concentrations than HbOC recipients (7.21 vs 28 micrograms/ml, P = 0.003) and lower bactericidal titers (3.18 vs. 15.4, not significant). We conclude that HbOC vaccine produced a significantly greater booster response than PRP-OMP vaccine when given at 12 to 15 months of age to children primed with two doses of PRP-OMP vaccine at 2 and 4 months of age.

Antibodies, Bacterial↗
PubMed1992

Utility of serum interleukin-6 for diagnosis of invasive bacterial disease in children.

STUDY OBJECTIVE: To evaluate measurement of interleukin-6 as a diagnostic test for the presence and severity of invasive bacterial disease. DESIGN: Prospective measurement of interleukin-6 in children with signs of sepsis. (Controls, retrospective from serum bank.) SETTING: Emergency department of an urban children's hospital. PARTICIPANTS: Twenty children with clinical signs of sepsis and 50 other febrile infants and toddlers with negative blood cultures. RESULTS: Eleven of the 20 patients had bacteriologically documented infections: four with meningitis and two with bacteremia caused by Neisseria meningitidis, three with meningitis caused by Haemophilus influenzae type b, and one each with meningitis and bacteremia caused by Streptococcus pneumoniae. Ten of these 11 had detectable interleukin-6. The geometric mean interleukin-6 level in these culture-positive patients was 407 pg/mL (95% confidence interval, 108 to 1,545); all three children with levels of more than 300 pg/mL developed septic shock, and one died. One of nine culture-negative patients with clinical signs of sepsis had detectable serum interleukin-6 (166 pg/mL), but none of 50 other febrile children without occult bacteremia did. The detection of interleukin-6 had a sensitivity of 91% and a specificity of 98% for invasive bacterial disease. CONCLUSION: High levels of interleukin-6 occur in children with septic shock, and the presence of interleukin-6 in serum is predictive for the isolation of bacteria from blood and/or spinal fluid.

Bacteremia↗
PubMed1992

Evaluation of bacterial polysaccharide immune globulin for the treatment or prevention of Haemophilus influenzae type b and pneumococcal disease.

A human hyperimmune globulin termed bacterial polysaccharide immune globulin (BPIG) has been prepared from plasma donors immunized with Haemophilus influenzae type b (Hib), pneumococcal, and meningococcal vaccines. At a dose of 0.5 ml/kg, BPIG increased levels of antibody to Hib by greater than 0.15 microgram/ml within 4-6 h and by 2-4 micrograms/ml at 72 h. Thereafter, antibody declined, with a mean half-life of 27 days. BPIG treatment of Apache infants did not impair their active antibody responses to concurrently administered diphtheria-tetanus-pertussis or Hib oligosaccharide-diptheria CRM197 conjugate vaccines. In high-risk Apache infants, BPIG given at 2, 6, and 10 months of age provided significant protection from invasive Hib infection during infancy. Thus, BPIG may have utility in the prevention of Hib infections in high-risk patients who cannot be immunized adequately with Hib conjugate vaccines.

Antibodies, Bacterial↗
PubMed1992

Maternal immunization with the capsular polysaccharide vaccine for Haemophilus influenzae type b.

Maternal immunization with the capsular polysaccharide (PRP) vaccine of Haemophilus influenzae type b has been shown to extend the time that protective levels of maternal antibody are detected in infants. In a randomized, blinded trial, PRP or placebo was administered uneventfully to 213 women in the third trimester of pregnancy. Infants born to PRP recipients had significantly higher levels of antibody to PRP than did infants born to placebo recipients: 2.73 micrograms/ml compared with 0.33 microgram/ml. It was estimated that infants of mothers who received the PRP vaccine would be protected for an average of 4 months compared to an average of only 2 months for those of mothers who received placebo. Infants were followed for invasive H. influenzae type b disease through the first year of life; none was detected.

Antibodies, Bacterial↗
PubMed1992

Prevention of Haemophilus influenzae type b infections in Apache and Navajo children.

Prospective surveillance of Haemophilus influenzae type b (Hib) disease has been done since 1981 in two high-risk populations, White Mountain Apaches and Navajos. The attack rate in children less than 5 years of age is 5-10 times higher than in the general US population. Three vaccines were evaluated. Unconjugated Hib capsular polysaccharide produced lower antibody responses in 18- and 24-month-old Apache infants than in white infants. HbOC (Hib oligosaccharide covalently linked to the nontoxic mutant diphtheria toxin CRM197) produced low antibody responses in Navajo infants after one or two doses but induced responses similar to those in whites after three doses. The responses of 18-month-old Navajos to HbOC were lower than those of whites, but most achieved protective levels. PRP-OMP (Hib capsular polysaccharide linked to the outer membrane protein complex of Neisseria meningitidis) produced good immune responses in 2-month-old Navajo and Apache infants after a single dose. This vaccine was greater than 90% efficacious in protecting Navajo infants from Hib disease when given at 2 and 4 months of age. Even a single dose achieved a high protective efficacy.

Antibodies, Bacterial↗
PubMed1992

Protective activity of a human respiratory syncytial virus immune globulin prepared from donors screened by microneutralization assay.

To explore the feasibility of preparing a human immune globulin specific for respiratory syncytial virus (RSV) by screening plasma donors, the ability of seven RSV antibody assays to identify plasma-yielding IgG with high virus-neutralizing and animal-protective activities was compared. IgG prepared from plasma units selected by microneutralization assay had significantly higher activity in protecting mice from respiratory RSV challenge than did IgGs prepared from plasmas selected by three direct ELISAs using purified F protein, G protein, or RSV-infected cell lysate, by two competitive ELISAs with RSV neutralizing monoclonal antibodies directed to the F2 or F3 epitopes of the F protein, or by plaque reduction neutralization. Relative to IgG made from unselected plasma, microneutralization-screened IgG was enriched fivefold by plaque-reduction neutralization assays done with or without complement. The microneutralization assay identified RSV antibodies with highest animal protective activity. This assay will be useful for identifying plasma donors for the preparation of a human immune globulin with high protective activity against RSV and deserves further evaluation for prediction of protective antibody concentrations in children.

Animals↗
PubMed1992

Limulus antilipopolysaccharide factor protects rabbits from meningococcal endotoxin shock.

Limulus antilipopolysaccharide factor (LALF), an 11.8-kDa peptide isolated from amebocytes of Limulus polyphemus, neutralizes meningococcal lipooligosaccharide (LOS)-induced gelation of limulus amebocyte lysate. Rabbits challenged with an LD90 of LOS (10 micrograms/kg) premixed with LALF in vitro (n = 10) had significantly higher mean arterial pressure, arterial pH, serum bicarbonate concentrations, and survival (90% vs. 8%, P = .005) than did rabbits challenged with LOS alone. Relative to untreated controls, rabbits pretreated with LALF intravenously (iv) at 1.2 mg/kg (n = 21) also had significant improvements in physiologic measurements and higher survival (52% vs. 8%, P = .003). Even when LALF (1.2 mg/kg iv) was given 1/2 h after LOS challenge, animals showed significant improvements in physiologic measurements and survival (33% vs. 8% in untreated controls P = .028). LALF-treated animals also had significantly lower circulating endotoxin activity and tumor necrosis factor concentrations. Thus, LALF attenuates the toxic effects of meningococcal LOS in rabbits even when administered after LOS challenge and deserves further evaluation as a potential therapeutic agent for treating gram-negative septic shock.

Animals↗
PubMed1992

Effect of pertussis toxin on susceptibility of infant rats to Haemophilus influenzae type b.

Pertussis toxin is an important virulence factor of Bordetella pertussis that may also contribute to the toxicity of pertussis vaccines. The effect of low doses of pertussis toxin on response to Haemophilus influenzae type b (Hib) infection was examined in infant rats. Pretreatment of rats with 10 or 100 ng of pertussis toxin increased blood bacterial concentration (P less than .01), serum endotoxin levels (P less than .01), and mortality (P less than .05) relative to saline pretreated controls challenged with 4 x 10(3) Hib intraperitoneally. The 100-ng dose of pertussis toxin, but not the 10-ng dose, increased the leukocyte count. Thus, doses of pertussis toxin less than the threshold dose for inducing leukocytosis may enhance the susceptibility of infant rats to Hib infections.

Animals↗
PubMed1992

Multicenter comparison of levels of antibody to the Neisseria meningitidis group A capsular polysaccharide measured by using an enzyme-linked immunosorbent assay.

There is no standard immunoassay for evaluating immune responses to meningococcal vaccines. We developed an enzyme-linked immunosorbent assay to measure total levels of antibody to Neisseria meningitidis group A capsular polysaccharide. Five laboratories measured the antibody levels in six paired pre- and postvaccination serum samples by using the enzyme-linked immunosorbent assay. Methylated human serum albumin was used to bind native group A polysaccharide to microtiter plate surfaces. The between-laboratory coefficients of variation for pre- and postvaccination sera had ranges of 31 to 91 and 17 to 31, respectively. The mean laboratory coefficients of variation for pre- and postvaccination sera, respectively, were 17 and 11 (Molecular Biology Laboratory, Centers for Disease Control), 12 and 15 (Immunodiagnostic Methods Laboratory, Centers for Disease Control), 22 and 19 (Dana-Farber Cancer Institute), 38 and 38 (Bacterial Polysaccharide Laboratory, U.S. Food and Drug Administration), and 11 and 10 (Praxis Biologics, Inc.). Standardization of this enzyme-linked immunosorbent assay should allow interlaboratory comparison of meningococcal vaccine immunogenicity, thus providing a laboratory-based assessment tool for evaluating meningococcal vaccines.

Adult↗
PubMed1991

Production of cell mass and pertussis toxin by Bordetella pertussis.

The cultivation of Bordetella pertussis affects production of pertussis toxin and biomass. Comparison of batch mode, chemostat operation and pHstat-turbidostatic control showed that productivities for the continuous process were greater than that for the batch operation. Continuous operation in balanced growth at the maximum specific growth rate, provided by the pHstat, resulted in the maximum specific production rate. Because of the strong association of pertussis toxin synthesis and cell growth, the concentration of toxin in the effluent of the continuous processes was greater than the maximum obtained in the batch bioprocess. An expanded Luedeking-Piret model of product formation kinetics fits the observed chemostat data and demonstrates that the production of pertussis toxin from the culture of B. pertussis is predominantly growth associated.

Bordetella pertussis↗
PubMed1991

Safety and immunogenicity of hydrogen peroxide-inactivated pertussis toxoid in 18-month-old children.

The immunogenicity and adverse effects of an acellular pertussis vaccine consisting of a purified pertussis toxin inactivated with hydrogen peroxide (PTxd) was evaluated. Children aged 15 to 30 months were injected with 10 (n = 33) or 50 micrograms (n = 34) of PTxd or with diphtheria and tetanus toxoids and whole cell pertussis vaccine (DTP) (n = 34). All children had previously received three doses of DTP during infancy. Both dosages of PTxd induced higher IgG antibody (p less than 0.05 for 10 micrograms dose and p less than 0.01 for 50 micrograms dose) and pertussis antitoxin responses (p less than 0.01 for 50 micrograms dose) than DTP. The 50 micrograms dose gave slightly higher (though not significantly) antibody responses than the 10 micrograms dose of PTxd. None of the vaccines induced detectable IgM or IgA antibody responses to pertussis toxin. At 24 h, local reactions occurred in none of the children injected with 10 micrograms PTxd, 12% with 50 micrograms PTxd and 78% with DTP. Fever at 24 h occurred in 13% after 10 micrograms PTxd, in none after 50 micrograms PTxd and in 53% after DTP. Recipients of DTP, but not of PTxd, had significant increases in neutrophils and decreases in lymphocytes and haematocrit at 24 h (all p less than 0.05). None of the groups showed changes in blood glucose at 24 h. PTxd induced pertussis toxin antibody levels similar to those observed in patients convalescing from natural pertussis. This acellular pertussis vaccine deserves further evaluation for safety and immunogenicity in infants and for efficacy in preventing pertussis.

Antibodies, Viral↗
PubMed1991

Effect of polymyxin B on experimental shock from meningococcal and Escherichia coli endotoxins.

Meningococcemia is the most frequent cause of septic shock in healthy children. To determine whether polymyxin B (PMB) might improve mortality from meningococcal shock, its protective activity was evaluated in rabbits challenged with an LD90 of meningococcal lipooligosaccharide (LOS) and compared with an LD80 of Escherichia coli O111:B4 lipopolysaccharide (LPS). PMB (5 mg/kg) administered intravenously 30 min before meningococcal LOS challenge had no significant effect on heart rate, mean arterial pressure, serum bicarbonate, serum tumor necrosis factor (TNF) levels, or survival relative to controls. However, PMB premixed with LOS in vitro increased serum bicarbonate levels (P less than .05) and improved 24-h survival (P less than .05). In contrast, PMB given before E. coli LPS challenge increased serum bicarbonate levels, decreased TNF levels, and improved 24-h survival (all, P less than .05). In vitro studies confirmed that PMB at 10 micrograms/ml neutralized E. coli LPS but not meningococcal LOS activity. Thus, pretreatment with PMB apparently protects rabbits against shock induced by E. coli LPS but not by meningococcal LOS.

Animals↗
PubMed1991

Serum anticapsular antibody response in the first week after immunization of adults and infants with the Haemophilus influenzae type b-Neisseria meningitidis outer membrane protein complex conjugate vaccine.

Eight healthy adults and 48 infants 2 and 4 months old were immunized with Haemophilus influenzae type b-Neisseria meningitidis outer membrane protein complex conjugate vaccine (PRP-OMP) to evaluate antibody kinetics in the first days after immunization. Five adults (63%) had some decrease in antibody, although the geometric mean did not decrease significantly. With one exception, the nadir occurred on postimmunization day 3. Seven had an antibody increase by day 7. Of the children, 6 (75%) of 8 and 17 (77%) of 23 had a decrease in antibody in serum obtained on day 2-3 after the first or second dose, respectively, the magnitude of which directly correlated with the preimmunization antibody concentration. However, the geometric mean did not decrease significantly. Within 1 week of immunization, 85% of infants had an increase in antibody, significantly greater after the second dose than after the first. A high concentration of maternally derived antibody before immunization correlated negatively with antibody response. Thus, a transient decrease in antibody occurs in most adults and infants 2-3 days after immunization with PRP-OMP followed by a prompt increase by day 7.

Adult↗
PubMed1990

Impaired antibody response to Haemophilus influenzae type b polysaccharide and low IgG2 and IgG4 concentrations in Apache children.

BACKGROUND AND METHODS: Because Native American children are at much higher risk for invasive Haemophilus influenzae type b infection than white children, we compared the antibody responses to H. influenzae type b polysaccharide vaccine in healthy Apache and white children. RESULTS: The concentrations of H. influenzae type b antibody after immunization with polysaccharide vaccine were approximately 10-fold lower in 24-month-old Apache children than in whites of a similar age (P less than 0.01). The decreased response involved H. influenzae type b antibodies of the IgG, IgM, and IgA classes. Concentrations of IgG antibody to tetanus toxoid did not differ significantly, and IgG antibodies to diphtheria toxoid were only twofold lower (P = 0.028). Although total IgG, IgM, and IgA levels were higher in two-year-old Apaches than in whites (all P less than 0.001), IgG2 and IgG4 subclasses were lower (both P less than 0.001). Among the Apaches, individual immunoglobulin levels and allotypes were not significantly correlated with their antibody responses to H. influenzae type b polysaccharide. CONCLUSIONS: Apache children have significant impairment of their antibody response to H. influenzae type b polysaccharide and little or no impairment of their antibody responses to protein toxoids. This immunodeficiency may explain the high incidence of H. influenzae type b infection in this population.

Antibodies, Bacterial↗