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Pulmonary vaccine lung imaging

Sunita Minz, Ravi Shankar Pandey
Pulmonary vaccination is one of the most promising routes for immunization owing to its noninvasive nature and induction of strong mucosal immunity and systemic response. In the present study, recombinant hepatitis B surface antigen loaded solid fat nanoemulsions (SFNs) as carrier system and monophosphoryl lipid A as an adjuvant-carrier system was prepared and evaluated as multiadjuvanted vaccine system for deep pulmonary vaccination. Deposition and clearance from the deep lung of rats were determined by gamma scintigraphy...
February 15, 2018: Journal of Pharmaceutical Sciences
Astrid E Lammers, Christian Apitz, Peter Zartner, Alfred Hager, Karl-Otto Dubowy, Georg Hansmann
Pulmonary hypertension (PH) is a condition of multiple aetiologies with underestimated prevalence and incidence. Indeed, despite access to modern therapies, pulmonary hypertensive vascular disease (PHVD) remains a progressive, usually life-limiting condition, severely impacting on the patients' well-being. We herein provide practical, expert consensus recommendations on the initial diagnostic work-up, clinical management and follow-up of children and adolescents with PH/PHVD, including a diagnostic algorithm...
May 2016: Heart: Official Journal of the British Cardiac Society
Daniel S Chertow, Jason Kindrachuk, Zong-Mei Sheng, Lindsey M Pujanauski, Kurt Cooper, Daniel Nogee, Marisa St Claire, Jeffrey Solomon, Donna Perry, Philip Sayre, Krisztina B Janosko, Matthew G Lackemeyer, Jordan K Bohannon, John C Kash, Peter B Jahrling, Jeffery K Taubenberger
BACKGROUND: Influenza results in up to 500,000 deaths annually. Seasonal influenza vaccines have an estimated 60% effectiveness, but provide little or no protection against novel subtypes, and may be less protective in high-risk groups. Neuraminidase inhibitors are recommended for the treatment of severe influenza infection, but are not proven to reduce mortality in severe disease. Preclinical models of severe influenza infection that closely correlate to human disease are needed to assess efficacy of new vaccines and therapeutics...
May 2016: Antiviral Research
Igor Kramnik, Gillian Beamer
A key aspect of TB pathogenesis that maintains Mycobacterium tuberculosis in the human population is the ability to cause necrosis in pulmonary lesions. As co-evolution shaped M . tuberculosis (M.tb) and human responses, the complete TB disease profile and lesion manifestation are not fully reproduced by any animal model. However, animal models are absolutely critical to understand how infection with virulent M.tb generates outcomes necessary for the pathogen transmission and evolutionary success. In humans, a wide spectrum of TB outcomes has been recognized based on clinical and epidemiological data...
March 2016: Seminars in Immunopathology
E Domingo-Musibay, C Allen, C Kurokawa, J J Hardcastle, I Aderca, P Msaouel, A Bansal, H Jiang, T R DeGrado, E Galanis
Osteosarcoma (OS) is the most common primary bone tumor affecting children and young adults, and development of metastatic disease is associated with poor prognosis. The purpose of this study was to evaluate the antitumor efficacy of virotherapy with engineered measles virus (MV) vaccine strains in the treatment of OS. Cell lines derived from pediatric patients with OS (HOS, MG63, 143B, KHOS-312H, U2-OS and SJSA1) were infected with MV expressing green fluorescent protein (MV-GFP) and MV-expressing sodium iodide symporter (MV-NIS) strains...
November 2014: Cancer Gene Therapy
Hongmei Nie, Jihong Dai
OBJECTIVE: To explore the value of pleural biopsy in the diagnosis of tuberculous pleurisy in children. METHOD: Fifty-one cases with tuberculous pleurisy, whose diagnosis was established according to the clinical diagnostic criteria of the child pulmonary tuberculosis formulated by the Chinese Medical Association (CMA) in 2006, after pleural biopsy hospitalized in Children's Hospital of Chongqing Medical University from Jan. 1, 2007 to Jan. 1, 2013 were enrolled into this study...
May 2014: Zhonghua Er Ke za Zhi. Chinese Journal of Pediatrics
E L Rayner, G R Pearson, G A Hall, R J Basaraba, F Gleeson, A McIntyre, S Clark, A Williams, M J Dennis, S A Sharpe
As part of a study to investigate early changes following exposure to aerosols of Mycobacterium tuberculosis (Mtb), 10 rhesus macaques (Macaca mulatta) were infected with high (731 colony forming units [cfu]), medium (70 cfu) or low (7 cfu) doses of Mtb, and tissues were examined at 2 and 3 weeks post infection (wpi). Clinical disease was not observed. Results of advanced imaging and pathological findings were compared with respect to the delivered dose and time post infection. Magnetic resonance imaging revealed lesions in the lungs at these early time points ex vivo immediately prior to detailed post-mortem examination in the absence of clinical disease...
November 2013: Journal of Comparative Pathology
J de Blic, A Deschildre, T Chinet
Post-infectious bronchiolitis obliterans (BO) is characterized by inflammatory and fibrotic lesions of small airways following a pulmonary infection and leading to some degree of airway obstruction. It represents a rare cause of chronic obstructive pulmonary disease, and is probably underestimated, especially when the lesions affect small areas of the lungs. The clinical features differ between children and adults. In children, adenovirus is the most frequently involved infectious agent, especially the more virulent serotypes 3, 7 and 21...
February 2013: Revue des Maladies Respiratoires
Edwin J B Veldhuis Kroeze, Koert J Stittelaar, Vera J Teeuwsen, Marcel L Dijkshoorn, Geert van Amerongen, Leon de Waal, Thijs Kuiken, Gabriel P Krestin, Jorma Hinkula, Albert D M E Osterhaus
Preclinical vaccine efficacy studies are generally limited to certain read out parameters such as assessment of virus titers in swabs and organs, clinical signs, serum antibody titers, and pathological changes. These parameters are not always routinely applied and not always scheduled in a logical standardized way. We used computed tomography (CT) imaging as additional and novel read out parameter in a vaccine efficacy study by quantifying alterations in aerated lung volumes in ferrets challenged with the 2009 pandemic A/H1N1 influenza virus...
December 7, 2012: Vaccine
Benedict Daniel Michael, Isabel Syndikus, Alistair Clark, Atik Baborie
UNLABELLED: A 75-year-old man, undergoing treatment for metastatic prostate cancer with a novel cancer cell vaccine, presented with a 4 week history of poor balance, gait disturbance and cognitive decline. Blood tests including HIV and onconeuronal and voltage gated potassium channel antibodies were normal. Computed tomography and two magnetic resonance images of the brain showed possible non-specific meningeal or vascular enhancement. Two cerebrospinal fluid analyses, including cytology, were negative, other than six lymphocytes in the former...
May 4, 2010: BMJ Case Reports
Sayma Rahman, Isabelle Magalhaes, Jubayer Rahman, Raija K Ahmed, Donata R Sizemore, Charles A Scanga, Frank Weichold, Frank Verreck, Ivanela Kondova, Jerry Sadoff, Rigmor Thorstensson, Mats Spångberg, Mattias Svensson, Jan Andersson, Markus Maeurer, Susanna Brighenti
To prevent the global spread of tuberculosis (TB) infection, a novel vaccine that triggers potent and long-lived immunity is urgently required. A plasmid-based vaccine has been developed to enhance activation of major histocompatibility complex (MHC) class I-restricted CD8⁺ cytolytic T cells using a recombinant Bacille Calmette-Guérin (rBCG) expressing a pore-forming toxin and the Mycobacterium tuberculosis (Mtb) antigens Ag85A, 85B and TB10.4 followed by a booster with a nonreplicating adenovirus 35 (rAd35) vaccine vector encoding the same Mtb antigens...
2012: Molecular Medicine
Mark A Miller, Jennifer M Stabenow, Jyothi Parvathareddy, Andrew J Wodowski, Thomas P Fabrizio, Xiaowen R Bina, Lillian Zalduondo, James E Bina
Intranasal instillation is a widely used procedure for pneumonic delivery of drugs, vaccine candidates, or infectious agents into the respiratory tract of research mice. However, there is a paucity of published literature describing the efficiency of this delivery technique. In this report we have used the murine model of tularemia, with Francisella tularensis live vaccine strain (FTLVS) infection, to evaluate the efficiency of pneumonic delivery via intranasal dosing performed either with differing instillation volumes or different types of anesthesia...
2012: PloS One
Ying Kong, Jeffrey D Cirillo
The slow growth rate of Mycobacterium tuberculosis hinders research progress, since estimating the bacterial numbers present in all experiments normally relies on determination of colony forming units on agar plates. M. tuberculosis colonies can take as long as four to six weeks to become visible. Whole animal imaging is an emerging technology that has broad applications in all areas of biological sciences, including monitoring infections. Imaging allows bacterial numbers to be determined in real-time for each infected animal, individually, which allows inter-animal variability to be observed and controlled for...
November 2010: Virulence
Ying Kong, Hequan Yao, Hongjun Ren, Selvakumar Subbian, Suat L G Cirillo, James C Sacchettini, Jianghong Rao, Jeffrey D Cirillo
The slow growth rate and genetic intractability of tubercle bacilli has hindered progress toward understanding tuberculosis, one of the most frequent causes of death worldwide. We overcame this roadblock through development of near-infrared (NIR) fluorogenic substrates for beta-lactamase, an enzyme expressed by tubercle bacilli, but not by their eukaryotic hosts, to allow real-time imaging of pulmonary infections and rapid quantification of bacteria in living animals by a strategy called reporter enzyme fluorescence (REF)...
July 6, 2010: Proceedings of the National Academy of Sciences of the United States of America
S A Sharpe, H McShane, M J Dennis, R J Basaraba, F Gleeson, G Hall, A McIntyre, K Gooch, S Clark, N E R Beveridge, E Nuth, A White, A Marriott, S Dowall, A V S Hill, A Williams, P D Marsh
The establishment of an aerosol challenge model in nonhuman primates (NHPs) for the testing of vaccines against Mycobacterium tuberculosis would assist the global effort to optimize novel vaccination strategies. The endpoints used in preclinical challenge studies to identify measures of disease burden need to be accurate and sensitive enough to distinguish subtle differences and benefits afforded by different tuberculosis (TB) vaccine regimens when group sizes are inevitably small. This study sought to assess clinical and nonclinical endpoints as potentially sensitive measures of disease burden in a challenge study with rhesus macaques by using a new protocol of aerosol administration of M...
August 2010: Clinical and Vaccine Immunology: CVI
S A Sharpe, E Eschelbach, R J Basaraba, F Gleeson, G A Hall, A McIntyre, A Williams, S L Kraft, S Clark, K Gooch, G Hatch, I M Orme, P D Marsh, M J Dennis
Sensitive and reproducible methods are needed to measure the impact on the host following experimental challenge with Mycobacterium tuberculosis, in order to determine the degree of protection conferred by new vaccines. Here we compare how well different clinical and post-mortem measures of disease burden predict the response by the host to increasing doses of M. tuberculosis in rhesus and cynomolgus macaques. The total lung and lesion volume was quantified from magnetic resonance imaging (MRI) digital stacks obtained from lungs of M...
November 2009: Tuberculosis
Martha A Hutchens, Kathryn E Luker, Joanne Sonstein, Gabriel Núñez, Jeffrey L Curtis, Gary D Luker
Innate immune responses are essential for controlling poxvirus infection. The threat of a bioterrorist attack using Variola major, the smallpox virus, or zoonotic transmission of other poxviruses has renewed interest in understanding interactions between these viruses and their hosts. We recently determined that TLR3 regulates a detrimental innate immune response that enhances replication, morbidity, and mortality in mice in response to vaccinia virus, a model pathogen for studies of poxviruses. To further investigate Toll-like receptor signaling in vaccinia infection, we first focused on TRIF, the only known adapter protein for TLR3...
2008: PLoS Pathogens
George Janossy, Simon M Barry, Ronan A M Breen, Gareth A D Hardy, Marc Lipman, Florian Kern
TB remains uncontrolled. In resource-rich countries, only approximately 60% of diagnoses are confirmed by culture. The number is lower in resource-poor environments. Huge scope therefore exists for alternative diagnostic strategies. Counting antigen-specific lymphocytes by virtue of cytokine production following 8-16 h stimulation with tuberculosis antigens is currently the strategy of choice. Several methods exist, including ELISA, ELISpots, and flow cytometry. Although it is clear that blood samples stimulated by ESAT-6 and CFP-10 antigens discriminate between TB infection and BCG vaccination, it is flow-cytometry that seems to be able to distinguish active TB disease from mere TB exposure...
2008: Cytometry. Part B, Clinical Cytometry
Ian M Orme
The tuberculosis vaccine field has blossomed in the past 10 years, with over a hundred new candidates going through animal model testing, and several now entering or approaching clinical trial evaluation. In this brief review the current animal screening models are discussed, as are the various types of new vaccines that have been developed. New approaches, especially in the area of BCG boosting in various prime/boost protocols, are starting to show considerable promise. More sophisticated readouts, including imaging approaches such as magnetic resonance imaging, and better definition of the immunopathology of the lung disease process, should help accelerate vaccine development even further in the next decade...
March 18, 2005: Vaccine
Susan L Kraft, Deanna Dailey, Matthew Kovach, Karen L Stasiak, Jamie Bennett, Christine T McFarland, David N McMurray, Angelo A Izzo, Ian M Orme, Randall J Basaraba
We utilized magnetic resonance imaging to visualize lesions in the lungs of guinea pigs infected by low-dose aerosol exposure to Mycobacterium tuberculosis. Lesions were prominent in such images, and colorized three-dimensional reconstructions of images revealed a very uniform distribution in the lungs. Lesion numbers after 1 month were approximately similar to the aerosol exposure algorithm, suggesting that each was established by a single bacterium. Numbers of lesions in unprotected and vaccinated animals were similar over the first month but increased thereafter in the control animals, indicating secondary lesion development...
October 2004: Infection and Immunity
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