19 research outputs found

    The Effect of Human Factor H on Immunogenicity of Meningococcal Native Outer Membrane Vesicle Vaccines with Over-Expressed Factor H Binding Protein

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    The binding of human complement inhibitors to vaccine antigens in vivo could diminish their immunogenicity. A meningococcal ligand for the complement down-regulator, factor H (fH), is fH-binding protein (fHbp), which is specific for human fH. Vaccines containing recombinant fHbp or native outer membrane vesicles (NOMV) from mutant strains with over-expressed fHbp are in clinical development. In a previous study in transgenic mice, the presence of human fH impaired the immunogenicity of a recombinant fHbp vaccine. In the present study, we prepared two NOMV vaccines from mutant group B strains with over-expressed wild-type fHbp or an R41S mutant fHbp with no detectable fH binding. In wild-type mice in which mouse fH did not bind to fHbp in either vaccine, the NOMV vaccine with wild-type fHbp elicited 2-fold higher serum IgG anti-fHbp titers (P = 0.001) and 4-fold higher complement-mediated bactericidal titers against a PorA-heterologous strain than the NOMV with the mutant fHbp (P = 0.003). By adsorption, the bactericidal antibodies were shown to be directed at fHbp. In transgenic mice in which human fH bound to the wild-type fHbp but not to the R41S fHbp, the NOMV vaccine with the mutant fHbp elicited 5-fold higher serum IgG anti-fHbp titers (P = 0.002), and 19-fold higher bactericidal titers than the NOMV vaccine with wild-type fHbp (P = 0.001). Thus, in mice that differed only by the presence of human fH, the respective results with the two vaccines were opposite. The enhanced bactericidal activity elicited by the mutant fHbp vaccine in the presence of human fH far outweighed the loss of immunogenicity of the mutant protein in wild-type animals. Engineering fHbp not to bind to its cognate complement inhibitor, therefore, may increase vaccine immunogenicity in humans

    Meningococcal Factor H Binding Proteins in Epidemic Strains from Africa: Implications for Vaccine Development

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    Epidemics of meningococcal meningitis are common in sub-Saharan Africa. Most are caused by encapsulated serogroup A strains, which rarely cause disease in industrialized countries. A serogroup A polysaccharide protein conjugate vaccine recently was introduced in some countries in sub-Saharan Africa. The antibodies induced, however, may allow replacement of serogroup A strains with serogroup W-135 or X strains, which also cause epidemics in this region. Protein antigens, such as factor H binding protein (fHbp), are promising for prevention of meningococcal serogroup B disease. These proteins also are present in strains with other capsular serogroups. Here we report investigation of the potential of fHbp vaccines for prevention of disease caused by serogroup A, W-135 and X strains from Africa. Four fHbp amino acid sequence variants accounted for 81% of the 106 African isolates studied. While there was little cross-protective activity by antibodies elicited in mice by recombinant fHbp vaccines from each of the four sequence variants, a prototype native outer membrane vesicle (NOMV) vaccine from a mutant with over-expressed fHbp elicited antibodies with broad protective activity. A NOMV vaccine has the potential to supplement coverage by the group A conjugate vaccine and help prevent emergence of disease caused by non-serogroup A strains

    Investigation of punchout distress of continuously reinforced concrete pavement

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    An in-depth study of factors and causes of punchout distress is presented. The study is based on a review of CRC pavement behavior under contraction restraint that encompassed several structural response models including two numerical models developed for CRC pavement structural response analysis. Each model was categorized according to different assumptions with regard to the bond stress distribution. Slab bending analysis models were also discussed in terms of transverse and longitudinal bending stresses under load. One of the models, the ILLI-SLAB program, was found to be versatile and provide accurate results. Other comparisons were also made with the structural response models on the basis of crack width, steel stresses, and concrete stresses. Distinct differences were noted between the TTICRCP model and the models which assume a uniformly distributed bond stress.Causes of punchout distress were investigated by punchout surveys conducted under this study of in service pavements. Various phases of the punchout distress were noted. Field data was also obtained from a coring program, a non-destructive testing program, and a pavement instrumentation program. All the collected data was summarized from which an account of a progressive mechanism of punchout distress was developed. Subbase erosion was found to be the primary cause of the punchout distress.Current design procedures were reviewed in light of the punchout study and several deficiencies noted. Failure modes representing various stages of punchout distress were formulated based on the punchout investigation. The failure modes provide a basis for thickness design in light of the punchout mechanism.Major findings from this study include: (1) fundamental cause of punchout distress is attributed to loss of subbase or non-uniform support, (2) loss of load transfer (which is primarily due to crack spalling) occurs as a part of the mechanism leading to the development of the punchout, and (3) large variability is associated with the cracking behavior of CRC pavement which is influenced by the intrinsic material properties of the concrete and by the environmental conditions.U of I OnlyETDs are only available to UIUC Users without author permissio

    Aggregate dilatometer device and methods of testing

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    Methods and devices for improved measurement of the thermal expansion and/or chemical reactivity of aggregates used in concrete and for similar substances. Aggregate is placed into the chamber of a metallic container having an enlarged opening. The aggregate is placed in a water bath, and a tightly sealable lid is placed onto the container. The lid carries a linear variable differential transducer (LVDT). A thermocouple for sensing temperature is also retained within the lid so that a sensor on the thermocouple contacts the water bath when the lid is secured onto the container. The LVDT is operationally interconnected with a storage or recording device. In a preferred construction the lid retains a tower member having a float that is freely moveably mounted upon a guide rod. Movement of the float is indicative of a volumetric change in the aggregate and water. In operation, the dilatometer device is used to determine the information relating to the amount of expansion or contraction of the aggregate in response to thermal changes. In addition, the devices and methods of the present invention are useful for determining the degree of reactivity of the aggregate. The degree of volumetric change for the aggregate alone maybe determined using equations that isolate and remove the expansion quotient of the water.U

    Aggregate dilatometer device and methods of testing

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    Methods and devices for improved measurement of the thermal expansion and/or chemical reactivity of aggregates used in concrete and for similar substances. Aggregate is placed into the chamber of a metallic container having an enlarged opening. The aggregate is placed in a water bath, and a tightly sealable lid is placed onto the container. The lid carries a linear variable differential transducer (LVDT). A thermocouple for sensing temperature is also retained within the lid so that a sensor on the thermocouple contacts the water bath when the lid is secured onto the container. The LVDT is operationally interconnected with a storage or recording device. In a preferred construction the lid retains a tower member having a float that is freely moveably mounted upon a guide rod. Movement of the float is indicative of a volumetric change in the aggregate and water. In operation, the dilatometer device is used to determine the information relating to the amount of expansion or contraction of the aggregate in response to thermal changes. In addition, the devices and methods of the present invention are useful for determining the degree of reactivity of the aggregate. The degree of volumetric change for the aggregate alone maybe determined using equations that isolate and remove the expansion quotient of the water.U

    Aggregate dilatometer device and methods of testing

    No full text
    Methods and devices for improved measurement of the thermal expansion and/or chemical reactivity of aggregates used in concrete and for similar substances. Aggregate is placed into the chamber of a metallic container having an enlarged opening. The aggregate is placed in a water bath, and a tightly sealable lid is placed onto the container. The lid carries a linear variable differential transducer (LVDT). A thermocouple for sensing temperature is also retained within the lid so that a sensor on the thermocouple contacts the water bath when the lid is secured onto the container. The LVDT is operationally interconnected with a storage or recording device. In a preferred construction the lid retains a tower member having a float that is freely moveably mounted upon a guide rod. Movement of the float is indicative of a volumetric change in the aggregate and water. In operation, the dilatometer device is used to determine the information relating to the amount of expansion or contraction of the aggregate in response to thermal changes. In addition, the devices and methods of the present invention are useful for determining the degree of reactivity of the aggregate. The degree of volumetric change for the aggregate alone maybe determined using equations that isolate and remove the expansion quotient of the water.U

    Precast Prestressed Concrete Pavement to Abate Settlement Problems Under Bridge Approach Slabs (FHWA-OK-16-08 2265)

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    The well-known bump-at-the-end-of-the-bridge often involving the joint between a bridge approach slab (BAS) and a bridge deck (as well as the associated slab cracking) has been a recurring issue over the years in many states. DOTs have reported differential settlement and cracking issues at this joint which has significantly reduced ride quality. Previous experience indicates that any Ònon-removalÓ conventional method of repair would not work well once erosion has set in; however, removing and replacing distressed BAS with cast-in-place (CIP) concrete usually require significant amount of time for curing, which leads to high costs of lane-closure and user delays. Therefore, a long-lasting and rapid repair method is needed to address this issue. This research focuses in part on the introduction of the precast concrete pavement slab for repairing distressed BASs and the elaboration of the design and construction procedures for precast BASs. Key elements within a BAS system are identified and design considerations provided for these elements for the prevention of erosion damage that may occur underneath the BASs. In addition, this research also provides a detailed design procedure for the stone column technique in order to address the potential for large settlement in the foundation of bridge embankments and proposes a procedure using non-destructive testing methods to rapidly characterize soil properties. This report contains three parts. The first part, ÒFinal ReportÓ, consists of Chapter 1 through Appendix D; the second part, from Chapter 9 to Appendix H, is the ÒBridge Approach Design GuidelineÓ; the third part is the ÒStone Column and Embankment Design GuidelineÓ which consists of Chapter 14 to Appendix N.Final Report, November 2014-October 2016N
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