Omar Qazi
Imperial College London
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Publication
Featured researches published by Omar Qazi.
Molecular Microbiology | 2009
Robert P. Fagan; David Albesa-Jové; Omar Qazi; Dmitri I. Svergun; Katherine A. Brown; Neil Fairweather
Clostridium difficile expresses a surface layer (S‐layer) which coats the surface of the bacterium and acts as an adhesin facilitating interaction of the bacterium with host enteric cells. The S‐layer contains a high‐molecular‐weight S‐layer protein (HMW SLP) and its low‐molecular‐weight partner protein (LMW SLP). We show that these proteins form a tightly associated non‐covalent complex, the H/L complex, and we identify the regions of both proteins responsible for complex formation. The 2.4 Å X‐ray crystal structure of a truncated derivative of the LMW SLP reveals two domains. Domain 1 has a two‐layer sandwich architecture while domain 2, predicted to orientate towards the external environment, contains a novel fold. Small‐angle X‐ray scattering analysis of the H/L complex shows an elongated molecule, with the two SLPs arranged ‘end‐to‐end’ interacting with each other through a small contact area. Alignment of LMW SLPs, which exhibit high sequence diversity, reveals a core of conserved residues that could reflect functional conservation, while allowing for immune evasion through sequence variation. These structures are the first described for the S‐layer of a bacterial pathogen, and provide insights into the assembly and biogenesis of the S‐layer.
Vaccine | 2011
Wildaliz Nieves; Saja Asakrah; Omar Qazi; Katherine A. Brown; Jonathan R. Kurtz; David P. AuCoin; James B. McLachlan; Chad J. Roy; Lisa A. Morici
Burkholderia pseudomallei, and other members of the Burkholderia, are among the most antibiotic-resistant bacterial species encountered in human infection. Mortality rates associated with severe B. pseudomallei infection approach 50% despite therapeutic treatment. A protective vaccine against B. pseudomallei would dramatically reduce morbidity and mortality in endemic areas and provide a safeguard for the U.S. and other countries against biological attack with this organism. In this study, we investigated the immunogenicity and protective efficacy of B. pseudomallei-derived outer membrane vesicles (OMVs). Vesicles are produced by Gram-negative and Gram-positive bacteria and contain many of the bacterial products recognized by the host immune system during infection. We demonstrate that subcutaneous (SC) immunization with OMVs provides significant protection against an otherwise lethal B. pseudomallei aerosol challenge in BALB/c mice. Mice immunized with B. pseudomallei OMVs displayed OMV-specific serum antibody and T-cell memory responses. Furthermore, OMV-mediated immunity appears species-specific as cross-reactive antibody and T cells were not generated in mice immunized with Escherichia coli-derived OMVs. These results provide the first compelling evidence that OMVs represent a non-living vaccine formulation that is able to produce protective humoral and cellular immunity against an aerosolized intracellular bacterium. This vaccine platform constitutes a safe and inexpensive immunization strategy against B. pseudomallei that can be exploited for other intracellular respiratory pathogens, including other Burkholderia and bacteria capable of establishing persistent infection.
European Journal of Immunology | 2005
John S. Tregoning; Simon Clare; Frances Bowe; Lorna Edwards; Neil Fairweather; Omar Qazi; Peter J. Nixon; Pal Maliga; Gordon Dougan; Tracy Hussell
Plant‐expressed vaccines may provide a unique opportunity for generating anti‐pathogen immunity, especially in countries where cold storage is lacking. In the following study, we show that soluble protein from tobacco leaves expressing fragment C of tetanus toxin protected mice against a lethal tetanus toxin challenge. More importantly, we show that a single intranasal (i.n.) vaccination was as efficient as oral delivery, inducing high levels of activated CD4+ T cells and anti‐toxin antibody. Unlike the oral route, i.n. delivery did not require the presence of adjuvant (cholera toxin). Indeed, addition of cholera toxin induced bystander immune responses to plant proteins as well. This is the first study documenting protective immunity by a single i.n. dose of plant vaccine. Plant‐based vaccines are promising because they are more heat stable, are easy to produce, cheap and do not require needles.
Vaccine | 2010
Sarah A. Ngugi; Valeria V. Ventura; Omar Qazi; Sarah V. Harding; G. Barrie Kitto; D. Mark Estes; Anne Dell; Richard W. Titball; Timothy P. Atkins; Katherine A. Brown; Paul G. Hitchen; Joann L. Prior
Burkholderia thailandensis is a less virulent close relative of Burkholderia pseudomallei, a CDC category B biothreat agent. We have previously shown that lipopolysaccharide (LPS) extracted from B. pseudomallei can provide protection against a lethal challenge of B. pseudomallei in a mouse model of melioidosis. Sugar analysis on LPS from B. thailandensis strain E264 confirmed that this polysaccharide has a similar structure to LPS from B. pseudomallei. Mice were immunised with LPS from B. thailandensis or B. pseudomallei and challenged with a lethal dose of B. pseudomallei strain K96243. Similar protection levels were observed when either LPS was used as the immunogen. This data suggests that B. thailandensis LPS has the potential to be used as part of a subunit based vaccine against pathogenic B. pseudomallei.
Nanomedicine: Nanotechnology, Biology and Medicine | 2015
Anthony E. Gregory; Barbara M. Judy; Omar Qazi; Carla A. Blumentritt; Katherine A. Brown; Andrew M. Shaw; Alfredo G. Torres; Richard W. Titball
UNLABELLED Burkholderia mallei are Gram-negative bacteria, responsible for the disease glanders. B. mallei has recently been classified as a Tier 1 agent owing to the fact that this bacterial species can be weaponised for aerosol release, has a high mortality rate and demonstrates multi-drug resistance. Furthermore, there is no licensed vaccine available against this pathogen. Lipopolysaccharide (LPS) has previously been identified as playing an important role in generating host protection against Burkholderia infection. In this study, we present gold nanoparticles (AuNPs) functionalised with a glycoconjugate vaccine against glanders. AuNPs were covalently coupled with one of three different protein carriers (TetHc, Hcp1 and FliC) followed by conjugation to LPS purified from a non-virulent clonal relative, B. thailandensis. Glycoconjugated LPS generated significantly higher antibody titres compared with LPS alone. Further, they improved protection against a lethal inhalation challenge of B. mallei in the murine model of infection. FROM THE CLINICAL EDITOR Burkholderia mallei is associated with multi-drug resistance, high mortality and potentials for weaponization through aerosol inhalation. The authors of this study present gold nanoparticles (AuNPs) functionalized with a glycoconjugate vaccine against this Gram negative bacterium demonstrating promising results in a murine model even with the aerosolized form of B. Mallei.
Frontiers in Microbiology | 2011
Gregory C. Whitlock; Mark D. Robida; Barbara M. Judy; Omar Qazi; Katherine A. Brown; Arpaporn Deeraksa; Katherine Taylor; Shane Massey; Andrey Loskutov; Alex Y. Borovkov; Kevin Brown; Jose A. Cano; D. Mitchell Magee; Alfredo G. Torres; D. Mark Estes; Kathryn Sykes
Burkholderia are highly evolved Gram-negative bacteria that primarily infect solipeds but are transmitted to humans by ingestion and cutaneous or aerosol exposures. Heightened concern over human infections of Burkholderia mallei and the very closely related species B. pseudomallei is due to the pathogens’ proven effectiveness as bioweapons, and to the increased potential for natural opportunistic infections in the growing diabetic and immuno-compromised populations. These Burkholderia species are nearly impervious to antibiotic treatments and no vaccine exists. In this study, the genome of the highly virulent B. mallei ATCC23344 strain was examined by expression library immunization for gene-encoded protective antigens. This protocol for genomic-scale functional screening was customized to accommodate the unusually large complexity of Burkholderia, and yielded 12 new putative vaccine candidates. Five of the candidates were individually tested as protein immunogens and three were found to confer significant partial protection against a lethal pulmonary infection in a murine model of disease. Determinations of peripheral blood cytokine and chemokine profiles following individual protein immunizations show that interleukin-2 (IL-2) and IL-4 are elicited by the three confirmed candidates, but unexpectedly interferon-γ and tumor necrosis factor-α are not. We suggest that these pathogen components, discovered using genetic immunization and confirmed in a conventional protein format, will be useful toward the development of a safe and effective glanders vaccine.
Transactions of The Royal Society of Tropical Medicine and Hygiene | 2008
Omar Qazi; Joann L. Prior; Barbara M. Judy; Gregory C. Whitlock; G. Barrie Kitto; Alfredo G. Torres; D. Mark Estes; Katherine A. Brown
We report the successful purification of lipopolysaccharide (LPS) from Burkholderia thailandensis, a Gram-negative bacterium, closely related to the highly pathogenic organisms B. pseudomallei and B. mallei. Burkholderia thailandensis LPS is shown to cross-react with rabbit and mouse sera obtained from inoculation with B. pseudomallei or B. mallei, respectively. These data suggest that B. thailandensis LPS shares similar structural features with LPS molecules from highly pathogenic Burkholderia species. This information may prove useful in ongoing efforts to develop novel vaccines and/or diagnostic reagents.
Infection and Immunity | 2006
Omar Qazi; Dorothea Sesardic; Rob Tierney; Zahra Söderbäck; Dennis T Crane; Barbara Bolgiano; Neil Fairweather
ABSTRACT In this study, the immunogenicities of the nontoxic HC fragment of tetanus toxin and derivatives lacking ganglioside binding activity were compared with that of tetanus toxoid after subcutaneous immunization of mice. Wild-type HC (HCWT) protein and tetanus toxoid both elicited strong antibody responses against toxoid and HC antigens and provided complete protection against toxin challenge. Mutants of HC containing deletions essential for ganglioside binding elicited lower responses than HCWT. HCM115, containing two amino acid substitutions within the ganglioside binding site, provided reduced protection against tetanus toxin challenge compared with HCWT, consistent with lower anti-HC and anti-toxoid antibody titers. Circular-dichroism spectroscopy and intrinsic fluorescence spectroscopy showed minimal structural perturbation in HCM115. We conclude that the presence of the ganglioside binding site within HC may be essential for induction of a fully protective anti-tetanus response comparable to that induced by tetanus toxoid by subcutaneous injection.
Procedia in Vaccinology | 2010
Gregory C. Whitlock; Arpaporn Deeraksa; Omar Qazi; Barbara M. Judy; Katherine Taylor; Katie L. Propst; Angie J. Duffy; Kate Johnson; G. Barrie Kitto; Katherine A. Brown; Steven W. Dow; Alfredo G. Torres; D. Mark Estes
Burkholderia mallei and B. pseudomallei are Gram-negative pathogenic bacteria, responsible for the diseases glanders and melioidosis, respectively. Furthermore, there is currently no vaccine available against these Burkholderia species. In this study, we aimed to identify protective proteins against these pathogens. Immunization with recombinant B. mallei Hcp1 (type VI secreted/structural protein), BimA (autotransporter protein), BopA (type III secreted protein), and B. pseudomallei LolC (ABC transporter protein) generated significant protection against lethal inhaled B. mallei ATCC23344 and B. pseudomallei 1026b challenge. Immunization with BopA elicited the greatest protective activity, resulting in 100% and 60% survival against B. mallei and B. pseudomallei challenge, respectively. Moreover, sera from recovered mice demonstrated reactivity with the recombinant proteins. Dendritic cells stimulated with each of the different recombinant proteins showed distinct cytokine patterns. In addition, T cells from immunized mice produced IFN-γ following in vitro re-stimulation. These results indicated therefore that it was possible to elicit cross-protective immunity against both B. mallei and B. pseudomallei by vaccinating animals with one or more novel recombinant proteins identified in B. mallei.
Journal of Mass Spectrometry | 2009
Omar Qazi; Paul G. Hitchen; Bérangère Tissot; Maria Panico; Howard R. Morris; Anne Dell; Neil Fairweather
Like many other bacterial cell surfaces, the cell wall of Clostridium difficile is also encapsulated by a proteinaceous paracrystalline layer, the surface (S)-layer. In many bacterial species, the S-layer proteins (SLPs) have been shown to be glycosylated, whereas in other species glycosylation is absent. Unusually, the S-layer of C. difficile is composed of two distinct proteins, the high-molecular weight (HMW) and low-molecular-weight (LMW) SLPs. Previous investigations have reported that one or both of these SLPs are glycosylated, though no definitive study has been conducted. We have used a variety of mass spectrometric approaches to analyse SLPs from a number of strains of C. difficile for the presence of associated glycans. Analysis of intact SLPs by matrix assisted laser desorption/ionisation time of flight (MALDI-ToF) mass spectrometry demonstrated that the observed molecular masses matched the predicted masses of the LMW and HMW SLPs. Furthermore, analysis of Cyanogen bromide (CNBr) and tryptic peptides displayed no evidence of post-translational modification. In the first in-depth study of its kind, we unequivocally demonstrate that the S-layer proteins from the C. difficile strains investigated are not glycosylated.