Relevant bibliographies by topics / Nontypeable Haemophilus influenzae

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Academic literature on the topic 'Nontypeable Haemophilus influenzae'

Author: Grafiati
Published: 4 June 2021
Last updated: 20 February 2023

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Journal articles on the topic "Nontypeable Haemophilus influenzae"

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Bakaletz, Lauren O., and Laura A. Novotny. "Nontypeable Haemophilus influenzae (NTHi)." Trends in Microbiology 26, no. 8 (August 2018): 727–28. http://dx.doi.org/10.1016/j.tim.2018.05.001.

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Clemans, Daniel L., Carl F. Marrs, Mayuri Patel, Michelle Duncan, and Janet R. Gilsdorf. "Comparative Analysis of Haemophilus influenzae hifA(Pilin) Genes." Infection and Immunity 66, no. 2 (February 1, 1998): 656–63. http://dx.doi.org/10.1128/iai.66.2.656-663.1998.

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ABSTRACT Adherence of Haemophilus influenzae to epithelial cells plays a central role in colonization and is the first step in infection with this organism. Pili, which are large polymorphic surface proteins, have been shown to mediate the binding of H. influenzae to cells of the human respiratory tract. Earlier experiments have demonstrated that the major epitopes of H. influenzae pili are highly conformational and immunologically heterogenous; their subunit pilins are, however, immunologically homogenous. To define the extent of structural variation in pilins, which polymerize to form pili, the pilin genes (hifA) of 26 type a to f and 16 nontypeable strains of H. influenzae were amplified by PCR and subjected to restriction fragment length polymorphism (RFLP) analysis with AluI and RsaI. Six different RFLP patterns were identified. Four further RFLP patterns were identified from published hifA sequences from five nontypeableH. influenzae strains. Two patterns contained only nontypeable isolates; one of these contained H. influenzaebiotype aegyptius strains F3031 and F3037. Another pattern contained predominantly H. influenzae type f strains. All other patterns were displayed by a variety of capsular and noncapsular types. Sequence analysis of selected hifA genes confirmed the 10 RFLP patterns and showed strong identity among representatives displaying the same RFLP patterns. In addition, the immunologic reactivity of pili with antipilus antisera correlated with the groupings of strains based on hifA RFLP patterns. Those strains that show greater reactivity with antiserum directed againstH. influenzae type b strain M43 pili tend to fall into one RFLP pattern (pattern 3); while those strains that show equal or greater reactivity with antiserum directed against H. influenzae type b strain Eagan pili tend to fall in a different RFLP pattern (pattern 1). Sequence analysis of representative HifA pilins from typeable and nontypeable H. influenzaeidentified several highly conserved regions that play a role in bacterial pilus assembly and other regions with considerable amino acid heterogeneity. These regions of HifA amino acid sequence heterogeneity may explain the immunologic diversity seen in intact pili.
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Rubin, L. G., K. Staiman, and N. Kamani. "Occult bacteremia with nontypeable Haemophilus influenzae." Journal of Clinical Microbiology 25, no. 7 (1987): 1314–15. http://dx.doi.org/10.1128/jcm.25.7.1314-1315.1987.

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LaCross, Nathan C., Carl F. Marrs, and Janet R. Gilsdorf. "Population structure in nontypeable Haemophilus influenzae." Infection, Genetics and Evolution 14 (March 2013): 125–36. http://dx.doi.org/10.1016/j.meegid.2012.11.023.

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Foxwell, A. Ruth, Jennelle M. Kyd, and Allan W. Cripps. "Nontypeable Haemophilus influenzae: Pathogenesis and Prevention." Microbiology and Molecular Biology Reviews 62, no. 2 (June 1, 1998): 294–308. http://dx.doi.org/10.1128/mmbr.62.2.294-308.1998.

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SUMMARY In this paper, we describe the ability of nontypeable Haemophilus influenzae (NTHi) to coexist with the human host and the devastating results associated with disruption of the delicate state of balanced pathogenesis, resulting in both acute and chronic respiratory tract infections. It has been seen that the strains of NTHi causing disease show a marked genetic and phenotypic diversity but that changes in the lipooligosaccharide (LOS) and protein size and antigenicity in chronically infected individuals indicate that individual strains of NTHi can remain and adapt themselves to avoid expulsion from their infective niche. The lack of reliance of NTHi on a single mechanism of attachment and its ability to interact with the host with rapid responses to its environment confirmed the success of this organism as both a colonizer and a pathogen. In vitro experiments on cell and organ cultures, combined with otitis media and pulmonary models in chinchillas, rats, and mice, have allowed investigations into individual interactions between NTHi and the mammalian host. The host-organism interaction appears to be a two-way process, with NTHi using cell surface structures to directly interact with the mammalian host and using secreted proteins and LOS to change the mammalian host in order to pave the way for colonization and invasion. Many experiments have also noted that immune system evasion through antigenic variation, secretion of enzymes and epithelial cell invasion allowed NTHi to survive for longer periods despite a specific immune response being mounted to infection. Several outer membrane proteins and LOS derivatives are discussed in relation to their efficacy in preventing pulmonary infections and otitis media in animals. General host responses with respect to age, genetic makeup, and vaccine delivery routes are considered, and a mucosal vaccine strategy is suggested.
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Kubiet, Martin, Reuben Ramphal, Allan Weber, and Arnold Smith. "Pilus-Mediated Adherence of Haemophilus influenzae to Human Respiratory Mucins." Infection and Immunity 68, no. 6 (June 1, 2000): 3362–67. http://dx.doi.org/10.1128/iai.68.6.3362-3367.2000.

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ABSTRACT Haemophilus influenzae, especially the nontypeable strains, are among the most common pathogens encountered in patients with chronic lung disease and otitis media. We and others have demonstrated that respiratory isolates of nontypeable H. influenzae bind to human mucins, but the mechanism of binding is not entirely clear. We have therefore examined the role of pili in the adherence of both type b and nontypeable H. influenzae to human respiratory mucins. We used isogenic H. influenzaestrains with a mutation in the structural gene for pilin (hifA), a laboratory H. influenzae strain transformed with a type b pilus gene cluster (from strain C54), antibodies raised against H. influenzae HifA, andEscherichia coli strains carrying a cloned type b pilus gene cluster (from strain AM30) in these studies. All bacteria lacking HifA or the pilus gene cluster had decreased adherence of piliatedH. influenzae to mucins, and Fab fragments of anti-HifA antibodies inhibited the adherence. E. coli strains carrying the cloned type b pilus gene cluster were six to seven times more adhesive than strains carrying the vector. The role of other putative adhesins was not examined and thus cannot be excluded, but these studies support a role for pili in the binding of H. influenzae to human respiratory mucins.
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Williams, Bryan J., Miriam Golomb, Thomas Phillips, Joshua Brownlee, Maynard V. Olson, and Arnold L. Smith. "Bacteriophage HP2 of Haemophilus influenzae." Journal of Bacteriology 184, no. 24 (December 15, 2002): 6893–905. http://dx.doi.org/10.1128/jb.184.24.6893-6905.2002.

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ABSTRACT Temperate bacteriophages effect chromosomal evolution of their bacterial hosts, mediating rearrangements and the acquisition of novel genes from other taxa. Although the Haemophilus influenzae genome shows evidence of past phage-mediated lateral transfer, the phages presumed responsible have not been identified. To date, six different H. influenzae phages are known; of these, only the HP1/S2 group, which lyosogenizes exclusively Rd strains (which were originally encapsulated serotype d), is well characterized. Phages in this group are genetically very similar, with a highly conserved set of genes. Because the majority of H. influenzae strains are nonencapsulated (nontypeable), it is important to characterize phages infecting this larger, genetically more diverse group of respiratory pathogens. We have identified and sequenced HP2, a bacteriophage of nontypeable H. influenzae. Although related to the fully sequenced HP1 (and even more so to the partially sequenced S2) and similar in genetic organization, HP2 has a few novel genes and differs in host range; HP2 will not infect or lysogenize Rd strains. Genomic comparisons between HP1/S2 and HP2 suggest recent divergence, with new genes completely replacing old ones at certain loci. Sequence comparisons suggest that H. influenzae phages evolve by recombinational exchange of genes with each other, with cryptic prophages, and with the host chromosome.
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Winter, Linda E., and Stephen J. Barenkamp. "HumanAntibodies Specific for the High-Molecular-Weight Adhesion Proteins ofNontypeable Haemophilus influenzae Mediate OpsonophagocyticActivity." Infection and Immunity 71, no. 12 (December 2003): 6884–91. http://dx.doi.org/10.1128/iai.71.12.6884-6891.2003.

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ABSTRACT The HMW1- and HMW2-like adhesion proteins of nontypeable Haemophilus influenzae are expressed by 75% of these strains, and antibodies directed against these proteins are protective in animal models of infection. The purpose of the present study was to define the functional activity of human antibodies specific for these proteins in an in vitro complement-dependent opsonophagocytic assay. Human promyelocytic cell line HL-60 served as the source of phagocytic cells, and a commercial preparation of intravenous immunoglobulin (IVIG) served as the source of human antibodies. High-molecular-weight (HMW) proteins were purified from four prototype nontypeable H. influenzae strains and used to prepare solid-phase affinity columns. IVIG was adsorbed on each column to remove strain-specific anti-HMW antibodies and to allow recovery of affinity-purified anti-HMW antibody fractions. Unadsorbed IVIG killed each of the prototype strains at titers of 1:80 to 1:320. HMW-adsorbed sera demonstrated fourfold decreases in opsonophagocytic titer against the homologous strains compared to unadsorbed IVIG. Affinity-purified anti-HMW antibody preparations demonstrated opsonophagocytic titers of 1:20 to 1:80 against the respective homologous strains and opsonophagocytic titers as high as 1:80 against heterologous strains. None of the affinity-purified anti-HMW antibody preparations was opsonophagocytic for a representative nontypeable H. influenzae strain that did not express HMW1- or HMW2-like proteins. These data demonstrate that human antibodies specific for the HMW1/HMW2-like adhesion proteins of nontypeable H. influenzae are opsonophagocytic and that such antibodies recognize epitopes shared by the HMW proteins of unrelated nontypeable H. influenzae strains. These results argue for continued investigation of the HMW1/HMW2-like proteins as potential vaccine candidates for prevention of disease due to nontypeable H. influenzae.
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SUNAKAWA, Keisuke, Yuriko TAKEUCHI, and Satoshi IWATA. "Nontypeable Haemophilus influenzae （NTHi） Epidemiology." Kansenshogaku Zasshi 85, no. 3 (2011): 227–37. http://dx.doi.org/10.11150/kansenshogakuzasshi.85.227.

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Smith-Vaughan, H. C., K. S. Sriprakash, J. D. Mathews, and D. J. Kemp. "Long PCR-ribotyping of nontypeable Haemophilus influenzae." Journal of clinical microbiology 33, no. 5 (1995): 1192–95. http://dx.doi.org/10.1128/jcm.33.5.1192-1195.1995.

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Dissertations / Theses on the topic "Nontypeable Haemophilus influenzae"

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Tsao, David L. "Serum resistance of an invasive nontypeable H. influenzae." Diss., Columbia, Mo. : University of Missouri-Columbia, 2004. http://hdl.handle.net/10355/5808.

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Thesis (M.S.)--University of Missouri-Columbia, 2004.
"December, 2004." The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Includes bibliographical references.
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Puig, Pitarch Carmen. "Nontypeable Haemophilus influenzae: colonization, infection and biofilm formation." Doctoral thesis, Universitat de Barcelona, 2015. http://hdl.handle.net/10803/311616.

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Haemophilus influenzae is an opportunistic pathogen that forms part of the human nasopharyngeal microbiota. This microorganism is classified into encapsulated and nonencapsulated or nontypeable (NTHi) isolates, depending on the presence of a polysaccharide capsule. Although H. influenzae is a common respiratory commensal, it is also able to cause several infections, especially in patients with comorbidities. The most common respiratory infections in which H. influenzae can be identified as the main etiological agent are exacerbations in patients with Chronic Obstructive Pulmonary Disease (COPD), community-acquired pneumonia (CAP), cystic fibrosis, and otitis media. In addition, this pathogen is also a common cause of invasive infections such as bacteraemia and meningitis. Before the introduction of the conjugate vaccine, H. influenzae serotype b (Hib) was the main cause of meningitis in children under five years. However, effective childhood vaccination has caused a dramatic reduction in Hib and allowed the expansion of NTHi, which is becoming more relevant in both respiratory and invasive infections. In this thesis, we studied three different aspects of the epidemiology of NTHi since the introduction of the vaccine. Our study focused on molecular genotyping, antimicrobial resistance and adhesion and biofilm formation of NTHi isolates from healthy children and from adult patients with CAP, COPD and invasive diseases. In the first part of this thesis, we set out to characterize the NTHi populations that are involved in adult infections in Bellvitge hospital. Furthermore, as humans are the only reservoir of NTHi, we aimed to identify the oropharyngeal carriage rate in healthy children attending day care centres in Oviedo. The aim of the second part of this thesis was to determine the antimicrobial susceptibility profile of clinical NTHi isolates, placing emphasis on the molecular characterization of B-lactam and fluoroquinolone resistance, the main antimicrobials used in the treatment of NTHi infections. The last part of this thesis focused on adhesion and biofilm formation. Biofilm is one of the mechanisms that microorganisms have developed in order to protect themselves and survive in hostile environments. Once the biofilm structure is formed, it is difficult to eliminate and, as a consequence, biofilm-associated infections commonly show recurrent symptoms. Although biofilm formation by NTHi remains controversial, biofilm-like structures have been observed in middle-ear mucosa in experimental chinchilla models of otitis media. Taken together, all the studies discussed in this thesis can improve our understanding of the clinical epidemiology of NTHi populations since the introduction of vaccination and of the mechanism of biofilm formation in clinical isolates of this microorganism.
Haemophilus influenzae és un patogen oportunista que forma part de la microbiota nasofaríngia humana. Aquest microorganisme es classifica en soques capsulades i no capsulades o no tipables (HiNT) depenent de la presència d’una càpsula polisacarídica. Tot i que H. influenzae és un comensal respiratori comú, posseeix la capacitat de causar diferents infeccions, especialment en pacients amb malalties de base. Les infeccions respiratòries més freqüents causades per H. influenzae són les exacerbacions agudes en pacients amb Malaltia Pulmonar Obstructiva Crònica (MPOC), pneumònia adquirida en la comunitat (PAC), exacerbacions en pacients amb fibrosis quística i otitis mitjana. A més, aquest patogen és també una causa freqüent de malalties invasives com bacterièmia i meningitis. Abans de la introducció de la vacuna conjugada, H. influenzae serotipus b (Hib) fou la causa principal de meningitis en nens/es menors de cinc anys d’edat. No obstant, l'efectiva vacunació ha causat un dramàtic descens del Hib permetent l’expansió dels HiNT, que s’estan convertint en un patogen més rellevant tant en infeccions respiratòries com en infeccions invasives. Els objectius plantejats en aquesta tesis, foren l’estudi de tres aspectes de la epidemiologia dels HiNT en l'etapa posterior a la introducció de la vacuna en Barcelona: la genotipificació molecular, la resistència antibiòtica i la formació de biofilm en soques d’HiNT aïllades de nens/es sans i de pacients adults amb PAC, MPOC i malalties invasives. L’objectiu de la primera part d’aquesta tesis fou caracteritzar les poblacions d’HiNT involucrades en les infeccions en pacients adults de l’hospital de Bellvitge així com la determinació de la freqüència de colonització orofaríngia d’HiNT en nens/es sans que van a llars d’infants en Oviedo. L’objectiu de la segona part de la tesis fou determinar els perfils de susceptibilitat antibiòtica dels aïllats clínics d’HiNT, emfatitzant en la caracterització molecular de la resistencia a B-lactàmics i fluoroquinolones, ja que són els antibiòtics més utilitzats en el tractament de les infeccions per HiNT. L’última part de la tesis està enfocada a l’estudi de l’adhesió i la formació de biofilm. El biofilm és un dels mecanismes que els microorganismes han desenvolupat per a la protecció i supervivència en ambients hostils. Una vegada l’estructura del biofilm està formada és molt difícil d’eliminar i, com a conseqüència, les infeccions associades a biofilm presenten símptomes recurrents. Tot i que la formació de biofilm per HiNT roman controvertida, estructures tipus biofilm s’han observat en la mucosa de l’oïda mitjana en models experimentals d’otitis mitjana en xinxilla. En conjunt, tots els estudis discutits en aquesta tesis contribueixen a ampliar el coneixement de la epidemiologia clínica, la resistència antibiòtica i la formació de biofilm de les poblacions d’HiNT en un període posterior a la introducció de la vacuna.
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Kunthalert, Duangkamol, and n/a. "Immunological and structural characterisation of the nontypeable Haemophilus influenzae vaccine protein OMP26." University of Canberra. Health Sciences, 2004. http://erl.canberra.edu.au./public/adt-AUC20060406.101830.

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Nontypeable Haemophilus influenzas (NTHi) is recognised as a significant human pathogen causing mild to severe respiratory tract infections. At present, no vaccine is available for prevention of infection caused by this pathogen. Several outer membrane proteins (OMPs) of NTHi and its lipooligosaccharide have been investigated as possible vaccine antigens against NTHi infections. Previous investigations in our laboratory have shown that OMP26 from an NTHi 289 strain was able to significantly enhance pulmonary clearance of NTHi in a rat model in which animals were immunised via intestinal Peyer's patches and then boosted intratracheally (Kyd and Cripps, 1998; El- Adhami et al., 1999). In recent studies, the OMP26, when used as a parenteral immunogen, was also highly effective at inducing immune responses that led to significantly enhanced clearance of the chinchilla nasopharynx (Kyd et al., 2003). These studies indicate significant potential of the OMP26 as a candidate vaccine antigen and warrant further investigations for development of a vaccine against NTHi. This thesis focussed on the immunological and structural characterisation of the NTHi vaccine candidate, OMP26. Peptides of OMP26 were used as tools to localise the immunologically important regions of the OMP26. Two different E. coli expression systems, the GST gene fusion and the 6xHis tagged systems, were employed to construct the OMP26 peptides. It was found in this study that, despite efforts to optimise the system, the GST-fusion protein system failed to produce consistent results for the purification and storage of the OMP26 peptides. In contrast, the 6xHis tagged system exhibited more reliable outcomes in the production of the recombinant OMP26 peptides and the stability of the stored purified peptides. As such, the purified OMP26 peptides from the 6xHis tagged system were chosen to map major regions of immunological significance for the OMP26 protein. The regions of the OMP26 which are involved in the induction of the acquired immune responses have been identified in the present study. Based on the antigen specific lymphocyte proliferation assay, the dominant T cell epitopes for OMP26 were located between amino acid residues 95 and 197 (T3+T4 region). These identified T cell epitopes exhibited the capability of efficient T cell activation, suggesting that the epitopes within the T3+T4 region potentially had the highest affinity for binding to the MHC molecules than did any other OMP26 region. Using two different assay systems, ELISA and BIA, the predominant B cell epitopes of OMP26 were located between amino acid residues 45 and 145 (T2+T3 region). This region was also found to be immunodominant across all animal species tested, and with all immunisation regimens used. Flow cytometry analysis also revealed that these particular epitopes were expressed on the surface of NTHi cells. By integration of the data obtained from these current experimental studies and the computational analysis of the OMP26 sequence, two hypothetical models of the OMP26 were also proposed in this study. The significant outcomes obtained in this thesis provide a better understanding of the specificity of the host immune responses to the OMP26 protein These findings provide great benefit not only for the development of a future NTHi vaccine but for the development of the peptide-based immunodiagnostic reagents as well. These diagnostic reagents will be valuable, in particular, for the evaluation of efficacy of an NTHi vaccine in humans that may include OMP26 or specific conformational structures. Future studies are still required to further define the minimum epitope length required for the B and T cell responses identified in this study. The significance of these responses in immune protection against NTHi infection also requires further investigations. Human immune responses also need to be determined, but this can only be achieved following clinical trial studies.
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Foxwell, Alice Ruth, and n/a. "Mechanisms of immunity to nontypeable Haemophilus influenzae in the lung." University of Canberra. Applied Science, 1998. http://erl.canberra.edu.au./public/adt-AUC20060710.142114.

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Pulmonary infection caused by nontypeable Haemophilus influenzae (NTHi) is a significant cause of morbidity and mortality in both industrialised and developing countries. Previous work from this group resulted in the development of a respiratory model in rodents which has precipitated studies into the pathogenesis of infection by NTHi and investigation of the humoral and cellular mechanisms by which the bacteria are cleared from the lung. Comparison of mucosally immunised with non-immunised animals has demonstrated that not only are bacteria cleared more rapidly from the lungs, but there is a more rapid response and resolution of inflammatory factors in the mucosally immunised animals following challenge with NTHi. This inflammatory response is partially regulated by the ability of the mucosally immunised animals to rapidly produce, then control the production of tumour necrosis factor (TNF)-a. The TNF-a is produced by both macrophages and type I pneumocytes in the alveoli and also by the endothelial cells lining the blood vessels in the lungs. Immunocytochemical studies have identified cellular subsets accumulating in the lung at various time points following infection. Marked differences in cellular infiltration into the lung tissue were noted between immunised and non-immunised animals after challenge with NTHi. Immunised animals demonstrated an early influx of macrophages, CD8+ T cells and Y8+ T cells, followed by enhanced expression of the MHC-II marker, cellular infiltration by polymorphonuclear leukocytes and finally an increased number of both B cells and CD4+ T cells. In contrast, non-immunised animals did not demonstrate any proliferation nor extravasation of lymphocytes or increased expression of MHC-II before total bacterial clearance had occurred. Polymorphonuclear leukocyte infiltration occurred in the non-immunised animals, however at a later time than that seen in immunised animals. Challenging rodents to establish persistent infection highlighted the inappropriately aggressive white blood cell response to an initial challenge when bacteria may be masked by other substances, followed by the inability to amplify the polymorphonuclear leukocyte response on repeated challenge with NTHi. This hyporesponsiveness in the macrophage population, shown by lack of detectable TNF-a production, concomitant with low numbers of NTHi resulted in a continuously high number of macrophages in the alveoli and the possibility of increased damage to the lung tissue. The requirement for cell surface TNF-a and CD8+ T cells to enhance the clearance of NTHi from the lungs further strengthens previous in vitro and in vivo findings of the possible significance of cellular invasion as a mechanism of pathogenicity for NTHi. This thesis has contributed to the understanding of both the immune response to and the pathogenicity mechanisms of pulmonary infection with NTHi. Kinetic studies identifying cellular responses and cytokine levels have emphasised the ability of mucosal immunisation to increase the rate of immune response and resolution of inflammation to NTHi infection in the lung. Observations demonstrating a requirement for macrophages and CD8+ T cells in mechanisms associated with enhancing NTHi clearance from the lung will lead to further investigations.
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Staffen, Dana Jean. "Environmental Factors Influence Nontypeable Haemophilus influenzae Biofilm Formation, Maturation and Gene Expression." The Ohio State University, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=osu1385497645.

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Ho, Derek K. "lgtC expression mediates complement resistance in nontypeable Haemophilus influenzae strain R2866 /." Thesis, Connect to this title online; UW restricted, 2006. http://hdl.handle.net/1773/9308.

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McGrath, John Francis, and n/a. "Immunomodulation in the context of developing a nontypeable Haemophilus influenzae vaccine." University of Canberra. Health Sciences, 2007. http://erl.canberra.edu.au./public/adt-AUC20070726.152419.

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One of the major challenges of vaccine development is the conservation of immunogenicity and protective efficacy through the stages of design, production, formulation and delivery. The critical issue is that how and in what form an antigen is taken up by antigen presenting cells for proteolytic processing and presentation to the immune system bound to MHC can have dramatic effects on the activation of Th cells to drive clonal responses and induction of immunological memory. Nontypeable Haemophilus influenzae (NTHi) is a pathogenic commensal of the human respiratory tract that causes diseases with enormous socioeoconomic burdens. There is no licensed vaccine, although the potential for vaccination with outer membrane components to reduce the incidence of disease caused by NTHi has recently been demonstrated in clinical trials. The issue of immunomodulation was explored in this thesis in the context of the further evaluation of a leading NTHi vaccine candidate, the outer membrane protein OMP26. The efficacy of recombinant OMP26 (rOMP26) against NTHi challenge has been previously demonstrated in mice, rats and chinchillas. In rats, efficacy was shown to be restricted to the precursor form (containing the signal peptide) and not the mature form of rOMP26. The immunodulatory effects of changes to the rOMP26 structure were further investigated in this thesis. A range of structural variants of rOMP26 were constructed in view of reducing extraneous plasmid-derived sequence from the antigen and to introduce a unique cysteine residue as a potential conjugate site for multivalent vaccine development (Chapter 2). It was demonstrated that minor structural changes to rOMP26 such as the addition, deletion, modification or relative positioning of a single amino acid or bulky group, designed to increase the efficiency of production or introduce (cysteine) conjugation sites, altered the expression of the protein in E. coli and the immunogenicity in Balb/C mice. Furthermore, in contradiction to the published report (El-Adhami et al. 1999) and a new study in rats (Chapter 3), there was no positive effect of the signal peptide in mice, with precursor and mature forms of rOMP26 equally immunogenic (Chapter 2). Following confirmation of the need to retain the signal peptide for the immunogenicity of rOMP26 in rats, a precursor form (rOMP26VTAL) in which the conserved n-region of the signal peptide was deleted, and shown to reduce the efficiency of the cleavage of the signal peptide by signal peptidase during protein overexpression in E. coli (Chapter 3). Not only did this deletion result in an increase the yield and stability of the purified precursor protein, but rOMP26VTAL was highly immunogenic and enhanced the clearance of NTHi from the lungs of challenged rats. The potential for signal peptides to be exploited as an immune-enhancing moiety in a proteinaceous vaccine is discussed. Following the development of rOMP26VTAL as a production optimised variant of rOMP26, the next step was to test the feasibility of rOMP26VTAL as a component of a multivalent vaccine (Chapter 4). Two chimeras were constructed with LB1(f)2,1,3, a trivalent synthetic B-cell epitope from the extracellular loop 3 region of the P5 fimbrin protein of NTHi, positioned at the N- or C-terminus of rOMP26VTAL. The solubility of rOMP26VTAL was affected by the fusion, with both chimera constructs expressed only in the insoluble fraction, thus requiring a denaturing protocol for purification. Although rLB1(f)2,1,3-OMP26VTAL was expressed and purified as a more stable protein and in greater yield than rOMP26VTAL-LB1(f)2,1,3, the relative positioning of the fusion was important and rOMP26VTAL-LB1(f)2,1,3 was significantly more immunogenic in rats than rLB1(f)2,1,3-OMP26VTAL. In addition, rOMP26VTALLB1( f)2,1,3, but not rLB1(f)2,1,3-OMP26VTAL induced a significant degree of bacterial clearance following pulmonary challenge with NTHi, in levels comparable to the highly efficacious rOMP26VTAL construct. In the third part of the thesis, bacterial ghosts were evaluated as a novel mucosal delivery technology for rOMP26VTAL and rOMP26VTAL-LB1(f)2,1,3, (Chapter 5). To mimic the natural presentation of OMP26 and P5 fimbrin antigens on the cell surface of NTHi, an OmpA� sandwich fusion surface display system was developed for the outer membrane expression of the OMP26 constructs in E. coli ghosts. Following gut immunisation, but not intranasal immunisation even when co-administered with the cholera toxin�derived adjuvant CTA1-DD, bacterial ghosts were successful at presenting OMP26VTAL and rOMP26VTAL-LB1(f)2,1,3 to the immune system for the induction of enhanced clearance of NTHi in the rat pulmonary challenge model. Although this study was the first to demonstrate enhanced bacterial clearance induced by heterologous antigens expressed in the outer membrane of bacterial ghosts, future studies with ghosts will require optimisation of the expression levels of the OmpA� fusion proteins possibly to avoid cross-reactive responses related to high doses of ghosts in the inoculum. This thesis presents data that both supports the further evaluation of rOMP26 constructs for clinical trials, and has demonstrated the significant effects of structural changes, method of production and delivery system can have on the immunogenicity of a candidate vaccine. Such knowledge will contribute to and provide some new approaches for enhancing the efficiency of vaccine development against a range of diseases including those caused by NTHi. Major Outcomes: 1. Demonstration that the immunogenicity of rOMP26 antigen constructs is affected by structural modifications and their positioning within the construct, and by the delivery system. 2. Development of rOMP26VTAL, an rOMP26 construct with the KNIAK sequence deletion of the signal peptide n-region. This protein retains the immunogenicity and protective efficacy of rOMP26, but is produced with reduced cleavage of the signal peptide, resulting in higher yields and a stable protein. Lacks extraneous plasmidderived multiple cloning site sequence, and is produced in high yield as a stable protein. 3. Construction of a NTHi rOMP26VTAL-LB1(f)2,1,3 chimera antigen that induced enhanced clearance of NTHi in an acute pulmonary challenge model in rats. 4. Development of an OmpA� surface display system for the expression of rOMP26 antigen constructs in the outer membrane of E. coli/bacterial ghosts 5. Bacterial ghosts were successful as delivery vehicles for rOMP26 candidate vaccine constructs when delivered in the gut.
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Webb, Dianne, and n/a. "Nontypeable Haemophilus influenzae outer membrane protein analysis, isolation, characterisation and vaccine potential." University of Canberra. Applied Science, 1998. http://erl.canberra.edu.au./public/adt-AUC20061110.105953.

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Heterogeneity in immunodominant outer membrane proteins has been proposed as a significant factor in the failure of an NTHi infection to induce immune protection against subsequent infections. This study has examined the vaccine potential of three outer membrane proteins in an attempt to identify conserved regions that could be targeted by an immune response after vaccination. The three proteins investigated were: TbpB, P5 and P48 (HI0164). The optimal route of immunisation in clearing a bolus inoculum of NTHi to the lung in the rat has been shown to be a combination of gut sensitisation with a respiratory boost and this regime was used in the present study. A panel of NTHi isolates was assessed to determine the frequency with which strains were able to bind transferrin and thus be targeted by a TbpBspecific immune response. A high proportion of strains was able to bind transferrin with similar frequencies in isolates associated with infection and those from normal throat swabs. A protocol was developed to purify nonlipidated recombinant TbpB from NTHi using a glutathione-Stransferase (GST)-rTbpB fusion protein and Glutathione-Sepharose affinity chromatography. Mucosal-directed immunisation with rTbpB significantly enhanced clearance of an NTHi challenge to the lung, however, whilst rTbpB-specific antibodies were cross-reactive on Western immunoblots, the cross-reactivity was variable in both transferrin binding inhibition assays and bactericidal activity. This suggested that the rTbpB-specific humoral response would be variable in the recognition of heterologous NTHi isolates. The secondary structure of P5 has been controversial with several reports suggesting that P5 was a fimbrin protein composed of coiled coils. In this present study the interstrain variation in P5 amongst isolates from diverse anatomical sites, as well as computer prediction methods and spectrophotometric analysis, generated a model of P5 based on the homologous E. coli protein, OmpA. This model suggested a B-barrel conformation with no evidence of coiled coils. Synthetic peptides corresponding to conserved regions of P5 that were thought to be surface exposed, as well as a region (H3) with some homology to a protective epitope in the P. aeruginosa protein, OprF, were then combined with a "promiscuous" T cell epitope from the measles virus F protein (MVF) and used for immunisation studies. Whilst variable protection was seen with the peptides, the MVF/H3 peptide was the most efficacious of the antigens assessed in this study in enhancing clearance of NTHi. This occurred in the absence of detectable peptide- or PS-specific antibody leading to the suggestion that cell mediated responses may have played an important role in enhancing clearance in this model. The highly conserved nature of the region in P5 represented by the H3 peptide suggests that further study should be focused on this peptide as a potential NTHi vaccine candidate. The last antigen, P48, is homologous to a A. pleuropneumoniae antigen, AopA, which has been proposed to have potential as a vaccine component against pleuropneumonia in pigs. Sequence analysis of the gene encoding P48 from several isolates showed that this protein was well conserved. Recombinant P48 was purified from a GST-rP48 fusion protein and used for immunisation, which also conferred significant protection. However, immunisation with rP48 was not as efficacious as immunisation with the MVF/H3 peptide. Whilst immunisation with rP48 induced high antibody titres, no bactericidal activity could be detected indicating that bactericidal antibody had not contributed to the observed clearance. In addition, the rP48- specific serum IgG was predominantly of the IgG2a isotype suggesting that Thl cell mediated responses had been induced by immunisation with rP48.
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Clarke, Jodie Louise, and n/a. "Regulation of Cytokines and Chemokines during Lung Infection with Nontypeable Haemophilus influenzae." University of Canberra. n/a, 2008. http://erl.canberra.edu.au./public/adt-AUC20081210.084252.

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An animal model of respiratory infection was used to determine the effect of various factors, thought to influence the ability of the host to clear bacteria, on the host?s innate response to an NTHi lung infection. Mucosal immunisation with NTHi has previously been shown to enhance the clearance of NTHi from the lung in an animal model of infection through the increased recruitment of phagocytes. Comparisons of cytokine and chemokine kinetic profiles were made in order to determine differences between innate and acquired immune response and the way in which mucosal immunisation controls the innate immune response to NTHi. Increased production of proinflammatory cytokines and chemokines in the early stages of NTHi lung infection enhanced the ability to clear bacteria from the rat lung in the immune animals through the increased recruitment of phagocytes to the site. Mucosal immunisation was found to alter the cytokine and chemokine mRNA profiles of CD4+ and CD8+ cells, with increased levels of MCP-1 protein being detected in both types of immune cells. An antecedent viral infection has been shown to increase the chance of developing a respiratory bacterial infection. The NTHi model of respiratory infection was used to characterise the effect that a viral infection had on the host response to the host?s innate response to a bacterial infection and the ability to clear the bacteria. The host?s ability to clear NTHi from the rat lung was enhanced by an antecedent viral infection through alterations to the innate immune response and the cytokine and chemokine kinetic profiles. The use of a mutant strain of NTHi deficient in a component of Lipooligosaccharide (LOS), Phosphorylcholine (ChoP), was utilised as a tool to characterise the innate immune response to LOS. Animals challenged with the LOS mutant strain had a reduced inflammatory response to NTHi through the decreased production of pro-inflammatory cytokines and chemokines and the reduced recruitment of phagocytes to the site of infection. This thesis has contributed valuable information to enable a better understanding of the host?s innate immune response to respiratory infection. This study has identified the role of cytokines and chemokines in the innate response to a respiratory bacterial infection and the enhanced ability of the host to clear NTHi from the lung.
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Månsson, Martin. "The structural diversity of lipopolysaccharides expressed by genetically defined clinical isolates of nontypeable Haemophilus influenzae /." Stockholm, 2003. http://diss.kib.ki.se/2003/91-7349-584-0.

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Book chapters on the topic "Nontypeable Haemophilus influenzae"

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Thanavala, Yasmin, and Amit A. Lugade. "Role of Nontypeable Haemophilus influenzae in Otitis Media and Chronic Obstructive Pulmonary Disease." In Recent Advances in Tonsils and Mucosal Barriers of the Upper Airways, 170–75. Basel: KARGER, 2011. http://dx.doi.org/10.1159/000324785.

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Spallone, Amy, and Daniel Musher. "Haemophilus." In Schlossberg's Clinical Infectious Disease, edited by Cheston B. Cunha, 931–35. Oxford University Press, 2021. http://dx.doi.org/10.1093/med/9780190888367.003.0138.

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This chapter examines Haemophilus influenzae, an extracellular, fastidious Gram-negative coccobacillus that commonly colonizes the human upper respiratory tract. Until the early 1980’s, an encapsulated form, H. influenzae type b, was the prevalent recognized pathogen, causing invasive disease such as meningitis or bacteteremic pneumonia; since that time, widespread use of a protein-conjugated capsular polysaccharide vaccine has largely eliminated this organism from the population. Most Haenophilus disease at the present time is due to unencapsulated (nontypeable) isolates which are common causes of respiratory tract infections, including otitis media, sinusitis, bronchitis, and pneumonia. These organisms are generally not invasive, i.e., they are not isolated from blood cultures, but morbidity may still be substantial. In the US, about one-third produce beta-lactamase, which is an important consideration in empiric therapy for disease that might be caused by nontypeable H. influenzae.
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Pelton, Stephen I. "Otitis." In Schlossberg's Clinical Infectious Disease, edited by Cheston B. Cunha, 47–55. Oxford University Press, 2021. http://dx.doi.org/10.1093/med/9780190888367.003.0006.

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This chapter looks at otitis. The clinical burden from acute (AOM) and chronic suppurative otitis media (CSOM) and their associated morbidities is substantial, especially in children. In industrialized countries, AOM remains the most frequent reason for pediatric office visits and recurrent otitis media (ROM), or persistent middle ear fluid and associated hearing loss, reduces quality of life. In developing nations, infectious complications of AOM include suppurative intracranial infection and CSOM with severe hearing loss. The prescription of antimicrobials increases bacterial resistance, so the role of antimicrobials in AOM has been reevaluated, using an evidence-based approach. ROM and CSOM usually begin in the first year of life, due to Streptococcus pneumoniae, nontypeable Haemophilus influenzae (NTHi), or Moraxella catarrhalis.
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Kyd, Jennelle M., Ajay Krishnamurthy, and Stephen Kidd. "Interactions and Mechanisms of Respiratory Tract Biofilms Involving Streptococcus Pneumoniae and Nontypeable Haemophilus Influenzae." In Microbial Biofilms - Importance and Applications. InTech, 2016. http://dx.doi.org/10.5772/63500.

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Conference papers on the topic "Nontypeable Haemophilus influenzae"

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Kimura, Genki, Yuki Nishimoto, Takahiro Nakaoki, Kazuhiro Ito, and Yasuo Kizawa. "Establishment of Nontypeable Haemophilus influenzae airway infection murine model." In ERS International Congress 2020 abstracts. European Respiratory Society, 2020. http://dx.doi.org/10.1183/13993003.congress-2020.2322.

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Ackland, Jodie, David Cleary, Myron Christodoulides, Tom Wilkinson, and Karl Staples. "Strain-dependent effects of Nontypeable Haemophilus influenzae (NTHi) on human macrophage function." In Abstracts from the 17th ERS Lung Science Conference: ‘Mechanisms of Acute Exacerbation of Respiratory Disease’. European Respiratory Society, 2019. http://dx.doi.org/10.1183/23120541.lungscienceconference-2019.pp135.

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Freeman, Christine M., Fernando J. Martinez, MeiLan K. Han, Stephen Chensue, Douglas A. Arenberg, Catherine A. Meldrum, Lisa McCloskey, and Jeffrey L. Curtis. "Lung CD8+ T Cells From COPD Subjects Respond To Nontypeable Haemophilus Influenzae Stimulation." In American Thoracic Society 2012 International Conference, May 18-23, 2012 • San Francisco, California. American Thoracic Society, 2012. http://dx.doi.org/10.1164/ajrccm-conference.2012.185.1_meetingabstracts.a1284.

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Kc, Rajendra, Nicholas M. Harkness, Louise A. Cooley, Belinda Mcewan, Graeme Zosky, Gunasegaran Karupiah, and Ronan F. O’Toole. "A simple workflow for comparative analysis of longitudinal isolates of nontypeable Haemophilus influenzae." In ERS International Congress 2019 abstracts. European Respiratory Society, 2019. http://dx.doi.org/10.1183/13993003.congress-2019.pa2899.

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Saliu, Fabio, Giulia Rizzo, Alessandra Bragonzi, Lisa Cariani, Daniela M. Cirillo, Carla Colombo, Valeria Daccò, et al. "The persistence of Nontypeable Haemophilus Influenzae fuels type 17 immunity in the lung." In ERS International Congress 2021 abstracts. European Respiratory Society, 2021. http://dx.doi.org/10.1183/13993003.congress-2021.pa2107.

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Stodden, H. S., F. Ritzmann, C. Herr, R. Bals, and C. Beisswenger. "Nontypeable Haemophilus influenzae supresses SP-B and SP-C expression in alveolar epithelial type II cells." In ERS Lung Science Conference 2021 abstracts. European Respiratory Society, 2021. http://dx.doi.org/10.1183/23120541.lsc-2021.40.

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Desai, Himanshu, Catherine Wrona, Timothy F. Murphy, and Sanjay Sethi. "Mechanisms Of Decline In Serum Bactericidal Activity For Nontypeable Haemophilus Influenzae (NTHI) In COPD Patients Chronically Colonized With NTHI." In American Thoracic Society 2010 International Conference, May 14-19, 2010 • New Orleans. American Thoracic Society, 2010. http://dx.doi.org/10.1164/ajrccm-conference.2010.181.1_meetingabstracts.a2911.

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Roscioli, E., M. Poh, A. Kicic, S. E. Lester, P. Nguyen, H. P. A. Jersmann, P. N. Reynolds, and S. Hodge. "Nontypeable Haemophilus Influenzae (NTHi) Exploits Disease-Related Defects in Xenophagy to Persist and Traffic Within the Epithelial Compartment During COPD." In American Thoracic Society 2019 International Conference, May 17-22, 2019 - Dallas, TX. American Thoracic Society, 2019. http://dx.doi.org/10.1164/ajrccm-conference.2019.199.1_meetingabstracts.a5376.

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Sethi, Sanjay, Catherine Wrona, Ellana Eberhardt, Lori Grove, Ganapathi I. Parameswaran, and Timothy Murphy. "Distinguishing Infecting (New) From Colonizing (Pre-Existing) Nontypeable Haemophilus Influenzae Strains At Exacerbation Of COPD By Molecular And Immunological Assays." In American Thoracic Society 2012 International Conference, May 18-23, 2012 • San Francisco, California. American Thoracic Society, 2012. http://dx.doi.org/10.1164/ajrccm-conference.2012.185.1_meetingabstracts.a4452.

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