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Vaccine lung pulmonary deposition study studies

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
Yoshita Bhide, Jasmine Tomar, Wei Dong, Jacqueline de Vries-Idema, Henderik W Frijlink, Anke Huckriede, Wouter L J Hinrichs
Administration of influenza vaccines to the lungs could be an attractive alternative to conventional parenteral administration. In this study, we investigated the deposition site of pulmonary delivered liquid and powder influenza vaccine formulations and its relation to their immunogenicity and protective efficacy. In vivo deposition studies in cotton rats revealed that, the powder formulation was mainly deposited in the trachea ( ∼ 65%) whereas the liquid was homogenously distributed throughout the lungs ( ∼ 96%)...
November 2018: Drug Delivery
Vesna Ilic, Vincent Dunet, Alain Le Pape, Mikael Buchs, Marek Kosinski, Angelika Bischof Delaloye, Stefan Gerber, John O Prior
AIMS: Vaccination by aerosol inhalation can be used to efficiently deliver antigen against HPV to mucosal tissue, which is particularly useful in developing countries (simplicity of administration, costs, no need for cold chain). For optimal immunological response, vaccine particles should preferentially be delivered to proximal bronchial airways. We aimed at quantifying the deposition of inhaled particles in central airways and peripheral lung, and to assess administration biosafety...
September 26, 2016: Nuklearmedizin. Nuclear Medicine
Michael G Sugiyama, Asela Gamage, Roman Zyla, Susan M Armstrong, Suzanne Advani, Andrew Advani, Changsen Wang, Warren L Lee
Lung injury after influenza infection is characterized by increased permeability of the lung microvasculature, culminating in acute respiratory failure. Platelets interact with activated endothelial cells and have been implicated in the pathogenesis of some forms of acute lung injury. Autopsy studies have revealed pulmonary microthrombi after influenza infection, and epidemiological studies suggest that influenza vaccination is protective against pulmonary thromboembolism; however, the effect of influenza infection on platelet-endothelial interactions is unclear...
February 15, 2016: Journal of Virology
Nitesh K Kunda, Iman M Alfagih, Eliane N Miyaji, Douglas B Figueiredo, Viviane M Gonçalves, Daniela M Ferreira, Sarah R Dennison, Satyanarayana Somavarapu, Gillian A Hutcheon, Imran Y Saleem
Pneumonia, caused by Streptococcus pneumoniae, mainly affects the immunocompromised, the very young and the old, and remains one of the leading causes of death. A steady rise in disease numbers from non-vaccine serotypes necessitates a new vaccine formulation that ideally has better antigen stability and integrity, does not require cold-chain and can be delivered non-invasively. In this study, a dry powder vaccine containing an important antigen of S. pneumoniae, pneumococcal surface protein A (PspA) that has shown cross-reactivity amongst serotypes to be delivered via the pulmonary route has been formulated...
November 30, 2015: International Journal of Pharmaceutics
Kathleen A Ross, Shannon L Haughney, Latrisha K Petersen, Paola Boggiatto, Michael J Wannemuehler, Balaji Narasimhan
Pulmonary immunization poses the unique challenge of balancing vaccine efficacy with minimizing inflammation in the respiratory tract. While previous studies have shown that mice immunized intranasally with F1-V-loaded polyanhydride nanoparticles are protected from a lethal challenge with Yersinia pestis, little is known about the initial interaction between the nanoparticles and immune cells following intranasal administration. Here, the deposition within the lung and internalization by phagocytic cells of polyanhydride nanovaccines encapsulating F1-V are compared with that of soluble F1-V alone or F1-V adjuvanted with monophosphoryl lipid A (MPLA)...
July 2014: Advanced Healthcare Materials
Simon Heuking, Barbara Rothen-Rutishauser, David Olivier Raemy, Peter Gehr, Gerrit Borchard
BACKGROUND: Plasmid DNA vaccination is a promising approach, but studies in non-human primates and humans failed to achieve protective immunity. To optimise this technology further with focus on pulmonary administration, we developed and evaluated an adjuvant-equipped DNA carrier system based on the biopolymer chitosan. In more detail, the uptake and accompanying immune response of adjuvant Pam3Cys (Toll-like receptor-1/2 agonist) decorated chitosan DNA nanoparticles (NP) were explored by using a three-dimensional (3D) cell culture model of the human epithelial barrier...
2013: Journal of Nanobiotechnology
Shumaila N M Hanif, Lucila Garcia-Contreras
Historically, pharmaceutical aerosols have been employed for the treatment of obstructive airway diseases, such as asthma and chronic obstructive pulmonary disease, but in the past decades their use has been expanded to treat lung infections associated with cystic fibrosis and other respiratory diseases. Tuberculosis (TB) is acquired after inhalation of aerosol droplets containing the bacilli from the cough of infected individuals. Even though TB affects other organs, the lungs are the primary site of infection, which makes the pulmonary route an ideal alternative route to administer vaccines or drug treatments...
2012: Frontiers in Cellular and Infection Microbiology
Huagang Zhang, Laibin Liu, Dong Yu, Ekambar R Kandimalla, Hui Bin Sun, Sudhir Agrawal, Chandan Guha
PURPOSE: Recent studies have shown that a new generation of synthetic agonist of Toll-like receptor (TLR) 9 consisting a 3'-3'-attached structure and a dCp7-deaza-dG dinucultodie shows more potent immunostimulatory effects in both mouse and human than conventional CpG oligonucleotides. Radiation therapy (RT) provides a source of tumor antigens that are released from dying, irradiated, tumor cells without causing systemic immunosuppression. We, therefore, examined effect of combining RT with a designer synthetic agonist of TLR9 on anti-tumoral immunity, primary tumor growth retardation and metastases in a murine model of lung cancer...
2012: PloS One
Georgiana Cheng, Shadi Swaidani, Manisha Sharma, Mark E Lauer, Vincent C Hascall, Mark A Aronica
Asthma is a chronic inflammatory disease of the airways characterized by airway remodeling, which includes changes in the extracellular matrix (ECM). However the role of the ECM in mediating these changes is poorly understood. Hyaluronan (HA), a major component of the ECM, has been implicated in asthma as well as in many other biological processes. Our study investigates the processes involved in HA synthesis, deposition, localization and degradation during an acute and chronic murine model of ovalbumin (OVA)-induced allergic pulmonary inflammation...
March 2011: Matrix Biology: Journal of the International Society for Matrix Biology
Hongbo Zhang, Hao Chen, Jingyi Niu, Yiqiang Wang, Lixin Xie
PURPOSE: Innate immunity had been thought to be critical in the pathogenesis and prognosis of fungal keratitis. This study was conducted to determine whether experimental Candida albicans keratitis (CaK) induces an adaptive immune response. METHODS: Experimental murine CaK was induced by intrastromal injection of C. albicans spores, and fungal pneumonia was induced by intranasal inhalation of spores. Active immunization was accomplished by subcutaneous injection of heat-inactivated spores...
June 2009: Investigative Ophthalmology & Visual Science
Mangalakumari Jeyanathan, Jingyu Mu, Kapilan Kugathasan, Xizhong Zhang, Daniela Damjanovic, Cherrie Small, Maziar Divangahi, Basil J Petrof, Cory M Hogaboam, Zhou Xing
Protection by parenteral immunization with plasmid DNA vaccines against pulmonary tuberculosis (TB) is very modest. In this study, we have investigated the underlying mechanisms for the poor mucosal protective efficacy and the avenues and mechanisms to improve the efficacy of a single i.m. immunization with a monogenic plasmid DNA TB vaccine in a murine model. We show that i.m. DNA immunization fails to elicit accumulation of Ag-specific T cells in the airway lumen despite robust T cell responses in the spleen...
October 15, 2008: Journal of Immunology: Official Journal of the American Association of Immunologists
Randall J Basaraba, Helle Bielefeldt-Ohmann, Ellie K Eschelbach, Claire Reisenhauer, Airn E Tolnay, Lauren C Taraba, Crystal A Shanley, Erin A Smith, Cathy L Bedwell, Elizabeth A Chlipala, Ian M Orme
The growth and virulence of Mycobacterium tuberculosis depends on its ability to scavenge host iron, an essential and limited micronutrient in vivo. In this study, we show that ferric iron accumulates both intra- and extra-cellularly in the primary lung lesions of guinea pigs aerosol-infected with the H37Rv strain of M. tuberculosis. Iron accumulated within macrophages at the periphery of the primary granulomatous lesions while extra-cellular ferric iron was concentrated in areas of lesion necrosis. Accumulation of iron within primary lesions was preceded by an increase in expression of heavy chain (H) ferritin, lactoferrin and receptors for transferrin, primarily by macrophages and granulocytes...
January 2008: Tuberculosis
Antoine Minne, Jamila Louahed, Sybille Mehauden, Benoît Baras, Jean-Christophe Renauld, Rita Vanbever
Pulmonary vaccination is a promising immunization route. However, there still remains a crucial need to characterize the different parameters affecting the efficacy of inhaled vaccination. This study aimed at assessing the impact of antigen distribution within the respiratory tract on the immune response to a monovalent A/Panama/2007/99 H3N2 influenza split virus vaccine administered to BALB/c mice. Varying the administration technique allowed the targeting of the vaccine to different sites of the mouse respiratory tract, i...
November 2007: Immunology
Homer L Twigg
The humoral, or antibody, immune response is essential for host defense against bacterial pathogens. The lung has the ability to respond quickly to some pathogens through stimulation of resident antigen-specific memory B cells. Alternatively, after exposure to a new pathogen, the lung can generate de novo both a systemic and local (mucosal) antibody response. The resulting production of antigen-specific IgG and IgA act in concert to help clear the invading pathogen and reduce subsequent colonization of respiratory epithelium...
2005: Proceedings of the American Thoracic Society
Allan L Coates, Graham Tipples, Kitty Leung, Michael Gray, Emily Louca et al.
OBJECTIVES: This study characterized the performance of the "Classical Mexican Device", which immunized 4 million children against measles, demonstrating the efficacy of aerosol vaccination. METHODS: Using plaque-forming units to quantify virus, the particle size distribution (Next Generation Pharmaceutical Impactor) and rate of output coupled with age specific patterns of breathing allowed the calculation of expected pulmonary deposition. RESULTS: The estimated immunization dose for infants was 30 pfu's, for small children 50, and for older children and adolescents it was 130 and 225, respectively...
March 6, 2006: Vaccine
Maytal Bivas-Benita, Raphaël Zwier, Hans E Junginger, Gerrit Borchard
In this report we present in detail a non-invasive pulmonary application method that can be a useful tool in studying drug and vaccine delivery to the lower airways. In this method the formulation is sprayed directly into the lungs of mice via the endotracheal route using a MicroSprayer aerolizer. Mean droplet size produced was 8 microm, appropriate for deposition in the large airways. Endotracheal application of suspension of fluorescent nanospheres, 200 nm in size, by this method resulted in nanoparticle deposition in the smaller airways (bronchi and bronchioles)...
October 2005: European Journal of Pharmaceutics and Biopharmaceutics
Lisa M Hodge, Jerry W Simecka
This study determined whether respiratory tract immunization protects against mycoplasma infection and compared preferential immunization of the upper respiratory tract (nasal) with upper and lower respiratory tract (nasal-pulmonary) immunization. Small volumes of inoculum preferentially deposited antigen and induced IgA responses in nasal passages. Larger inoculums deposited antigen in both the upper and lower respiratory tracts, generating corresponding IgA responses. Mice were given nasal or nasal-pulmonary immunizations with Mycoplasma pulmonis antigen alone or with cholera toxin (CT), and resistance to infection was determined...
July 15, 2002: Journal of Infectious Diseases
W J Metzger, J W Nyce
The recent increase in the prevalence of and mortality from asthma has inspired several new molecular techniques to improve treatment. Because asthma is a disease of gene polymorphism, gene therapy is unlikely to be effective. Alternative methods use oligonucleotides (ODNs) in the form of (1) DNA vaccination expressing CpG motifs that mimic bacterial DNA or (2) antisense ODNs inhaled and locally deposited into pulmonary airways to specifically modulate receptors for inflammatory mediators. DNA vaccination, a form of "molecular immune surveillance," attenuates a TH2 predominance...
August 1999: Journal of Allergy and Clinical Immunology
S S Botros, B L Doughty, Z A Shaker, M M Akl, R Sharmy, T M Diab, H I Hassanein
This study was undertaken to study the efficacy of praziquantel (PZQ) in potentially tolerized Schistosoma mansoni infected, egg-injected C57BL/6 mice, receiving multiple administrations of soluble egg antigen (SEA) intravenously (i.v.). Four animal groups were studied. Experimental group I received four injections of SEA (10 micrograms) intravenously on days -7, -5, -3 and -2 before infection and PZQ orally (500 mg/kg over two consecutive days 7 weeks post-infection. Three control groups received the following treatment: group II received the same tolerizing dose of SEA without PZQ, group III received PZQ in the same dose and at the same timing...
December 1996: International Journal of Immunopharmacology
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