Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0348321 (Haemophilus)
 15,372 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Haemophilus influenzae vaccine consisting of purified type b capsular polysaccharide (polyribosylribitol-phosphate [PRP]) was shown in Finland to be protective, with 90% efficacy in children older than 18 to 23 months of age. However, a wide range of estimates of vaccine efficacy has been reported in the United States after its licensure in 1985. These estimates range from -55% to +89%. In addition, the PRP vaccine was not effective in children younger than 18 months of age, in whom 70% to 80% of meningitis cases occur. A further development was the introduction of H influenzae type b polysaccharide-protein conjugate vaccines such as the PRP-D. These conjugate vaccines were found to be more immunogenic than PRP vaccine in children of all ages. Two doses of PRP-D in infants 7 months of age and older induced antibody levels equal to or greater than levels in infants 24 months of age who received the PRP vaccine alone. Recently, Eskola et al reported that repeat vaccinations with PRP-D at 3, 4, 6, and 14 months of age was 83% protective (95% confidence interval, 26% to 96%). Yet PRP-D vaccine elicits only low serum antibody levels in infants younger than 7 months of age. Because of the discrepancy in efficacy results for the PRP vaccine in the United States and Finland and the lack of data about the protective efficacy of PRP-D vaccine in infants in the United States, the PRP-D vaccine is currently recommended only for children 18 months of age or older.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Haemophilus influenzae type b conjugate vaccine (meningococcal protein conjugate): immunogenicity and safety at various doses. 210 20

Immunization with Haemophilus influenzae type b capsular polysaccharide (polyribosylribitol-phosphate [PRP]) has resulted in limited and variable antibody radioimmunoassay in infants younger than 2 years of age. Although an H influenzae type B vaccine has been in use for several years, it is not used now for the age group at greatest risk for disease. In an effort to enhance immunogenicity, PRP has been coupled to various carrier proteins and to an outer membrane protein complex (OMPC) from Neisseria meningitidis group B. The latter approach has yielded a vaccine that elicits a good antibody response after a single 15-micrograms dose of vaccine in infants as young as 2 months of age, as measured by radioimmunoassay and immune bacteriolysis. In this report we describe the results of a pilot study using this H influenzae type B conjugate vaccine, PedvaxHIB, in children from 2 months to 4 years of age. Three different vaccine lots were examined for consistency of response. Sera were measured for antibody levels by radioimmunoassay and for functional activity using an opsonophagocytic assay using human adult neutrophils. These assays correlated well and demonstrated the excellent immune response and biologic activity of sera from infants vaccinated with this unique H influenzae type B conjugate vaccine.
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PMID:Opsonophagocidal activity in sera from infants and children immunized with Haemophilus influenzae type b conjugate vaccine (meningococcal protein conjugate). 210 21

A cost-benefit analysis of Haemophilus influenzae type b disease preventive strategies was updated to consider evaluation of the H. influenzae type b polysaccharide-diphtheria toxoid conjugate vaccine (PRP-D) and H. influenzae type b oligosaccharide-mutant diphtheria toxin conjugate vaccine (HbOC) for children at 18 months of age. The analysis was done from the perspective of society as a whole. The economic costs of H. influenzae type b disease in the 1988 United States birth cohort would be $2.546 billion (1988 U.S. dollars) in the absence of preventive efforts. If 60% of all children could be vaccinated with PRP-D or HbOC at 18 months of age, this strategy would save $207.1 million ($88.22 savings/vaccinee; $43,605 cost/case prevented; 3.57/1 benefit-to-cost ratio) under base case model assumptions. Universal PRP-D or HbOC vaccination at 18 months of age would prevent 1845 cases of invasive H. influenzae type b disease. The break-even efficacy for universal PRP-D or HbOC vaccination at 18 months of age was 22.7%. We conclude that, under the model base case assumptions, universal PRP-D or HbOC vaccination at 18 months of age is sufficiently efficacious so that the costs of vaccination would be more than offset by decreased medical care costs for treating H. influenzae type b disease.
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PMID:Cost-benefit analysis of Haemophilus influenzae type b prevention: conjugate vaccination at eighteen months of age. 211 Jun 51

To find a wide spectrum vaccine against bacteraemic disease in childhood, we immunized 293 Finnish children at 24 months of age intramuscularly with different combinations of the currently available vaccines, namely Haemophilus influenzae type b polysaccharide-protein conjugate vaccine (PRP-D) mixed with meningococcal and/or pneumococcal capsular polysaccharide vaccines. All the vaccines were immunogenic. The increase in antibody concentration after vaccinations was not affected by the number of polysaccharide antigens. Although no serious reactions were seen, the frequency of both local and fever reactions was greater in groups that received several vaccine antigens. Halving of the vaccine dose decreased the reactogenicity without impairing the immunogenicity.
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PMID:Reactogenicity and immunogenicity of combined vaccines for bacteraemic diseases caused by Haemophilus influenzae type b, meningococci and pneumococci in 24-month-old children. 211 Jul 3

Polysaccharide-protein conjugate vaccines made with different carriers vary in their ability to elicit antipolysaccharide IgG antibody responses in young infants and an adult mouse model, suggesting that the carrier proteins used in the conjugate vaccines differ in their ability to act as carriers, or that additional mechanisms of immunogenicity play a role. A conjugate vaccine of Haemophilus influenzae PRP coupled to the outer membrane protein complex (OMPC) of Neisseria meningitidis serogroup B is immunogenic in children as young as 2 mo of age and is immunogenic in infant rhesus monkeys, an animal model for infant humans. In the present study, PRP-OMPC was found to induce efficient IgM to IgG switching of anti-PRP serum antibody in adult mice, whereas PRP conjugated to two other protein carriers did not. Thus the PRP-OMPC conjugate was examined in order to determine why PRP coupled to OMPC was so immunogenic, even more immunogenic than conjugates made with other carrier proteins. The OMPC carrier differs from the other protein carriers in that the proteins are present in a liposomal form containing lipids (including LPS) derived from the outer membrane of N. meningitidis. We studied the OMPC to see whether the different components or the nature of the OMPC carrier could contribute to its enhanced immunogenicity. Specifically we evaluated the OMPC for both classic Th cell carrier activity and adjuvanticity, and the LPS component of OMPC for systemic polyclonal B cell activation. Carrier recognition of the OMPC moiety of PRP-OMPC was demonstrated. In addition the PRP-OMPC conjugate vaccine was observed to have adjuvant properties for both T cell-dependent and T cell-independent Ag in the absence of LPS-induced systemic polyclonal B cell activation. These observations suggest that in addition to functioning as a classic protein carrier whereby the proteins in OMPC provide Th cell epitopes, the OMPC also has adjuvant activity that distinguishes it from other protein carriers and may contribute to the increased immunogenicity of PRP-OMPC conjugates in animal models.
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PMID:Immunogenicity of a Haemophilus influenzae polysaccharide-Neisseria meningitidis outer membrane protein complex conjugate vaccine. 212 Mar 44

The affinities of IgG antibodies to Haemophilus influenzae b capsular polysaccharide (polyribosyl ribitol phosphate [PRP]) elicited 1 month after immunization of 47 infants 2-greater than 18 months of age with a PRP-outer membrane protein conjugate (PRP-OMP) were measured by ELISA. Thirty-four sera had affinities distributed normally about a logarithmic mean of 3.2 x 10(5) l/mol, but 13 samples had undetectable affinities (less than 10(4) l/mol). Median affinities of sera from children 2-6 (1.5 x 10(5) l/mol) and 7-11 months of age (1.6 x 10(5) l/mol) were significantly greater than the median affinities of sera from infants 12-18 (1.8 x 10(4) l/mol) or greater than 18 months of age (4.2 x 10(4) l/mol). Sera from children greater than 18 months of age vaccinated with PRP conjugated to diphtheria toxoid had a median affinity of 6.1 x 10(4) l/mol, equivalent to that of the same age group vaccinated with PRP-OMP. Children vaccinated with PRP conjugate vaccines may produce antibodies of very low affinity, a finding that may have significance for protection from invasive disease.
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PMID:Antibody affinity in infants after immunization with conjugated capsular polysaccharide from Haemophilus influenzae type b. 223 Feb 42

To evaluate the persistence of antibody after Haemophilus influenzae type b polysaccharide vaccine (PRP) and H influenzae type b polysaccharide diphtheria toxoid conjugate vaccine (PRP-D), a group of 141 infants initially immunized between 15 and 24 months of age were studied 1 year later. One month after immunization with PRP, the man anti-PRP antibody level was 0.27 microgram/mL and 1 year later was 0.29 microgram/mL (not significant). In the group immunized with PRP-D, the levels were 1.34 micrograms/mL and 1.20 micrograms/mL (not significant), respectively. To evaluate immunogenicity and safety of a booster immunization 1 year after initial vaccination, subjects were randomly assigned to receive saline, PRP, or PRP-D. In addition, 73 age-matched previously unimmunized subjects were vaccinated with PRP or PRP-D. In all groups, adverse reactions were minor and resolved by 48 hours. Subjects receiving booster immunization with PRP or PRP-D had significantly greater antibody responses than children of the same age receiving their first dose of vaccine. The highest antibody levels were achieved in children initially immunized with PRP-D, regardless of whether the booster vaccine was PRP (112.8 micrograms/mL) or PRP-D (122.0 micrograms/mL) (not significant). Antibody levels after booster vaccine were significantly lower in those initially given PRP compared with those initially given PRP-D but significantly higher than in age-matched previously unimmunized control subjects (PRP booster 3.16 micrograms/mL vs control of 0.62 microgram/mL [P less than .05]; PRP-D booster 12.31 micrograms/mL vs control 2.31 micrograms/mL [P less than .01]).
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PMID:Persistence of antibody and booster responses to reimmunization with Haemophilus influenzae type b polysaccharide and polysaccharide diphtheria toxoid conjugate vaccines in children initially immunized at 15 to 24 months of age. 230 81

We estimated the relative protective efficacy of Haemophilus influenzae type b polysaccharide (PRP) vaccine and PRP-diphtheria toxoid-conjugate (PRP-D) vaccine using data from reports of cases of invasive Haemophilus disease occurring in vaccinated children submitted to the Food and Drug Administration, Rockville, Md, and Washington University, St Louis, Mo. During the first 13 months following licensure of each of the vaccines, there were 127 cases reported in recipients of PRP vaccine vs 17 cases in recipients of PRP-D vaccine. The total number of reported cases for each vaccine is not necessarily comparable, since the extent of vaccine use in the population and the extent of reporting of cases may have been different during the two periods. However, the proportion of reported cases occurring equal to or 14 days or more after vaccination (a period considered sufficient to develop immunity) was significantly greater for PRP vaccine (106 [83%] of 127 cases) compared with PRP-D vaccine (7 [41%] of 17 cases). Based on the ratio of late-onset to early-onset cases observed for PRP vaccine, we would have expected 50 late-onset cases after PRP-D vaccination. Since only 7 late-onset PRP-D vaccine failures were reported (86% fewer than expected), the data suggest that PRP-D vaccine was more effective in preventing disease 14 days or more after vaccination than was PRP vaccine.
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PMID:Protective efficacy of Haemophilus influenzae type b polysaccharide-diphtheria toxoid-conjugate vaccine. 230 34

A defect in antibody response to immunization with Haemophilus influenzae type b (Hib) capsular polysaccharide vaccine has been reported in children with recurrent infections and normal immunoglobin levels. We identified 15 children, aged 2 to 6 years, with this defect, and we evaluated their response to immunization with an Hib capsular oligosaccharide diphtheria CRM197 protein-conjugate vaccine (HbOC). The children received a series of three vaccines: HbOC at 0 and 8 weeks, and the Hib polysaccharide vaccine at 16 weeks. Levels of antibody to the Hib capsular polysaccharide (polyribosyl ribitol phosphate, PRP) and to diphtheria toxoid were obtained before and 4 weeks after each vaccination. The geometric mean serum anti-PRP concentration was 0.17 microgram/ml before immunization and 29.3 micrograms/ml after the second HbOC immunization (week 12). All 15 children had postvaccination anti-PRP antibody levels greater than 1.0 microgram/ml after receiving the second HbOC (week 12). In addition, booster responses were observed after the second Hib conjugate in 13 of the patients and after the Hib polysaccharide in four of the patients. All patients with low preimmunization diphtheria titers had a response to the diphtheria toxoid. These results suggest that conjugation of Hib polysaccharide with diphtheria CRM197 overcomes the defective antibody response to Hib oligosaccharide in children who are initially observed with recurrent infections and inability to respond to the Hib polysaccharide vaccine.
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PMID:Response to a Haemophilus influenzae type b diphtheria CRM197 conjugate vaccine in children with a defect of antibody production to Haemophilus influenzae type b polysaccharide. 233 68

Complement-mediated bactericidal and opsonic activity of IgG1 and IgG2 antibodies to Haemophilus influenzae type b polysaccharide (polyribosyl ribitol phosphate [PRP]) were investigated. The antibody sources were IgG1 or IgG2 subclass polyclonal antibody fractions prepared by immunoabsorption of sera from adults immunized with PRP or PRP-diphtheria toxoid conjugate vaccine or clonally purified anti-PRP antibodies from eight adults immunized with PRP vaccine. In bactericidal assays using an inoculum of 3 x 10(3) colony-forming units (cfu)/ml, twofold lower concentrations of IgG1 compared with IgG2 antibody were required for 50% killing. With approximately 10(6) cfu/ml, IgG1 antibody killed 3 logs more of bacteria than were killed by comparable concentrations of IgG2 antibody. The IgG1 antibody also required lower concentrations of complement than did the IgG2 antibody for comparable bacteriolytic activity. Clonally purified IgG1 and IgG2 anti-PRP antibodies from most individuals showed similar relative differences in bactericidal activity. IgG1 anti-PRP antibody was also more efficient than IgG2 anti-PRP antibody in enhancing the uptake of radiolabeled type b H. influenzae by human polymorphonuclear leukocytes in the presence of complement and in protecting infant rats from developing bacteremia. However, the differences in opsonic or protective activity of the two subclasses were smaller than the differences in bactericidal activity. Thus, IgG1 anti-PRP antibody is functionally more effective than IgG2 antibody, but it is likely that both subclasses can confer protection against disease.
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PMID:Bactericidal and opsonic activity of IgG1 and IgG2 anticapsular antibodies to Haemophilus influenzae type b. 235 93


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