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Pulmonary vaccine delivery

Mohammad Nasiruddin, Md Kausar Neyaz, Shilpi Das
Tuberculosis, commonly known as TB, is the second most fatal infectious disease after AIDS, caused by bacterium called Mycobacterium tuberculosis. Prolonged treatment, high pill burden, low compliance, and stiff administration schedules are factors that are responsible for emergence of MDR and XDR cases of tuberculosis. Till date, only BCG vaccine is available which is ineffective against adult pulmonary TB, which is the most common form of disease. Various unique antibodies have been developed to overcome drug resistance, reduce the treatment regimen, and elevate the compliance to treatment...
2017: Tuberculosis Research and Treatment
Kristin L Griffiths, Mushtaq Ahmed, Shibali Das, Radha Gopal, William Horne, Terry D Connell, Kelly D Moynihan, Jay K Kolls, Darrell J Irvine, Maxim N Artyomov, Javier Rangel-Moreno, Shabaana A Khader
The development of a tuberculosis (TB) vaccine that induces sterilizing immunity to Mycobacterium tuberculosis infection has been elusive. Absence of sterilizing immunity induced by TB vaccines may be due to delayed activation of mucosal dendritic cells (DCs), and subsequent delay in antigen presentation and activation of vaccine-induced CD4(+) T-cell responses. Here we show that pulmonary delivery of activated M. tuberculosis antigen-primed DCs into vaccinated mice, at the time of M. tuberculosis exposure, can overcome the delay in accumulation of vaccine-induced CD4(+) T-cell responses...
December 22, 2016: Nature Communications
Swarna Bale, Amit Khurana, A Shiva Shankar Reddy, Mandip Singh, Chandraiah Godugu
Research in novel drug delivery systems is being explored competitively in order to attain maximum therapeutic effect while minimizing the adverse effects. Despite several advancements in pharmaceutical formulations, one of the major challenges still persisting is sustained drug release. Microencapsulation enacts as an intelligent approach with a strong therapeutic impact and is in demand globally in medical technology due to its specific and attractive properties, including biocompatibility, stability, target specificity, uniform encapsulation, better compliance, and controlled and sustained release patterns that are responsible for diminishing the toxicity and dosage frequency...
2016: Critical Reviews in Therapeutic Drug Carrier Systems
Guixiang Dai, Hamada F Rady, Weitao Huang, Judd E Shellito, Carol Mason, Alistair J Ramsay
Tuberculosis remains a major public health hazard worldwide, with neonates and young infants potentially more susceptible to infection than adults. BCG, the only vaccine currently available, provides some protection against tuberculous meningitis in children but variable efficacy in adults, and is not safe to use in immune compromised individuals. A safe and effective vaccine that could be given early in life, and that could also potentiate subsequent booster immunization, would represent a significant advance...
December 7, 2016: Vaccine
Umesh Wadgave, L Nagesh
Today tobacco use is the single greatest preventable cause of death in the world. Tobacco use is often incorrectly perceived to be solely a personal choice. This is contradicted by the fact that when fully aware of the health impact, most tobacco users want to quit but find it difficult to stop due to the addictiveness of nicotine. Henceforth, Nicotine replacement therapy (NRT) came into existence which temporarily replaces much of the nicotine from tobacco to reduce motivation to consume tobacco and nicotine withdrawal symptoms, thus easing the transition from cigarette smoking to complete abstinence...
July 2016: International Journal of Health Sciences
Nazrul Islam, Vito Ferro
The advent of biodegradable polymer-encapsulated drug nanoparticles has made the pulmonary route of administration an exciting area of drug delivery research. Chitosan, a natural biodegradable and biocompatible polysaccharide has received enormous attention as a carrier for drug delivery. Recently, nanoparticles of chitosan (CS) and its synthetic derivatives have been investigated for the encapsulation and delivery of many drugs with improved targeting and controlled release. Herein, recent advances in the preparation and use of micro-/nanoparticles of chitosan and its derivatives for pulmonary delivery of various therapeutic agents (drugs, genes, vaccines) are reviewed...
August 14, 2016: Nanoscale
Mengying Zhou, Mingjuan Jiang, Chenyan Ren, Sijing Liu, Qikang Pu, Howard Goldfine, Hao Shen, Chuan Wang
Listeria monocytogenes (LM) vectors have shown much promise in delivery of viral and tumor antigens for the development of vaccines. L. ivanovii (LI) is a closely related bacterium with a similar intracellular life cycle that may offer advantages over LM because it is not a human pathogen, but can infect other animal species. Recent studies show that recombinant LI expressing Mycobacterium tuberculosis antigens is effective in inducing protective immunity in mouse models, demonstrating the potential of LI as a live vaccine vector...
2016: Frontiers in Microbiology
Abdul Muheem, Faiyaz Shakeel, Mohammad Asadullah Jahangir, Mohammed Anwar, Neha Mallick, Gaurav Kumar Jain, Musarrat Husain Warsi, Farhan Jalees Ahmad
In the modern world, a number of therapeutic proteins such as vaccines, antigens, and hormones are being developed utilizing different sophisticated biotechnological techniques like recombinant DNA technology and protein purification. However, the major glitches in the optimal utilization of therapeutic proteins and peptides by the oral route are their extensive hepatic first-pass metabolism, degradation in the gastrointestinal tract (presence of enzymes and pH-dependent factors), large molecular size and poor permeation...
July 2016: Saudi Pharmaceutical Journal: SPJ: the Official Publication of the Saudi Pharmaceutical Society
Daryan A Kaveh, M Carmen Garcia-Pelayo, Paul R Webb, Esen E Wooff, Véronique S Bachy, Philip J Hogarth
Boosting BCG using heterologous prime-boost represents a promising strategy for improved tuberculosis (TB) vaccines, and adenovirus (Ad) delivery is established as an efficacious boosting vehicle. Although studies demonstrate that intranasal administration of Ad boost to BCG offers optimal protection, this is not currently possible in cattle. Using Ad vaccine expressing the mycobacterial antigen TB10.4 (BCG/Ad-TB10.4), we demonstrate, parenteral boost of BCG immunised mice to induce specific CD8(+) IFN-γ producing T cells via synergistic priming of new epitopes...
July 25, 2016: Vaccine
Thaigarajan Parumasivam, Rachel Yoon Kyung Chang, Sharif Abdelghany, Tian Tian Ye, Warwick John Britton, Hak-Kim Chan
Tuberculosis (TB) is an intracellular infectious disease caused by the airborne bacterium, Mycobacterium tuberculosis. Despite considerable research efforts, the treatment of TB continues to be a great challenge in part due to the requirement of prolonged therapy with multiple high-dose drugs and associated side effects. The delivery of pharmacological agents directly to the respiratory system, following the natural route of infection, represents a logical therapeutic approach for treatment or vaccination against TB...
July 1, 2016: Advanced Drug Delivery Reviews
Kelly A Prendergast, Claudio Counoupas, Lisa Leotta, Carolina Eto, Wilbert Bitter, Nathalie Winter, James A Triccas
Defining the function and protective capacity of mycobacterial antigens is crucial for progression of tuberculosis (TB) vaccine candidates to clinical trials. The Ag85B protein is expressed by all pathogenic mycobacteria and is a component of multiple TB vaccines under evaluation in humans. In this report we examined the role of the BCG Ag85B protein in host cell interaction and vaccine-induced protection against virulent Mycobacterium tuberculosis infection. Ag85B was required for macrophage infection in vitro, as BCG deficient in Ag85B expression (BCG:(Δ85B)) was less able to infect RAW 264...
May 17, 2016: Vaccine
Lina Shi, Lianying Zhang, Changcai Li, Xiaoyan Hu, Xiaolei Wang, Qing Huang, Gengyin Zhou
BACKGROUND: Besides being the world's most widely used vaccine, BCG is the most controversial vaccine in current use. Estimates of protection impaired by BCG against pulmonary TB vary from nil to 80%. Dietary zinc deficiency has been confirmed to impair the immune function of animals. However, knowledge about effects of mild dietary zinc deficiency and the time of vaccination on BCG vaccine responsiveness in offspring and adult rats is limited. This work investigated the consequences of feeding zinc deficient and normal zinc diets to rats during gestation, infancy or adulthood on the immune responses to BCG vaccination...
March 2016: Tuberculosis
Sandra Jesus, Edna Soares, João Costa, Gerrit Borchard, Olga Borges
Among new strategies to increase hepatitis B virus (HBV) vaccination, especially in developing countries, the development of self-administered vaccines is considered one of the most valuable. Nasal vaccination using polymeric nanoparticles (NPs) constitutes a valid approach to this issue. In detail, poly-ε-caprolactone (PCL)/chitosan NPs present advantages as a mucosal vaccine delivery system: the high resistance of PCL against degradation in biological fluids and the mucoadhesive and immunostimulatory properties of chitosan...
May 17, 2016: International Journal of Pharmaceutics
Ikwo K Oboho, Carrie Reed, Paul Gargiullo, Michelle Leon, Deborah Aragon, James Meek, Evan J Anderson, Patricia Ryan, Ruth Lynfield, Craig Morin, Marisa Bargsten, Shelley M Zansky, Brian Fowler, Ann Thomas, Mary Lou Lindegren, William Schaffner, Ilene Risk, Lyn Finelli, Sandra S Chaves
BACKGROUND: We describe the impact of early initiation of influenza antiviral treatment among pregnant women hospitalized with laboratory-confirmed influenza during the 2010-2014 influenza seasons. METHODS: Severe influenza was defined as illness with ≥1 of the following: intensive care unit admission, need for mechanical ventilation, respiratory failure, pulmonary embolism, sepsis, or death. Within severity stratum, we used parametric survival analysis to compare length of stay by timing of antiviral treatment, adjusting for underlying conditions, influenza vaccination, and pregnancy trimester...
August 15, 2016: Journal of Infectious Diseases
Arman Mosavat, Saman Soleimanpour, Hadi Farsiani, Hamid Sadeghian, Kiarash Ghazvini, Mojtaba Sankian, Saeid Amel Jamehdar, Seyed Abdolrahim Rezaee
Tuberculosis (TB) remains a major health problem worldwide. Currently, the Bacilli Calmette-Guérin (BCG) is the only available licensed TB vaccine, which has low efficacy in protection against adult pulmonary TB. Therefore, the development of a safe and effective vaccine against TB needs global attention. In the present study, a novel multi-stage subunit vaccine candidate from culture filtrate protein-10 (CFP-10) and heat shock protein X (HspX) of Mycobacterium tuberculosis fused to the Fc domain of mouse IgG2a as a selective delivery system for antigen-presenting cells (APCs) was produced and its immunogenicity assessed...
April 2016: Infection, Genetics and Evolution
Camilla Foged
In the past century, vaccines have contributed to a significant improvement in global public health by preventing a number of infectious diseases. Despite this, the vaccine field is still facing challenges related to incomplete vaccine coverage and persistent difficult vaccine targets, such as influenza, tuberculosis, and Ebola, for which no good universal vaccines exist. At least two pharmaceutical improvements are expected to help filling this gap: i) The development of thermostable vaccine dosage forms, and ii) the full exploitation of the adjuvant technology for subunit vaccines to potentiate strong immune responses...
2016: Current Pharmaceutical Design
Farideh Shiehzadeh, Mohsen Tafaghodi
Delivery to the lungs is an efficient way to deliver drugs directly to the site of action or to the blood circulation. Because of limitations of direct administration of free drugs, particulate drug delivery systems such as DPI formulations based on nanoparticles (NPs) have been of interest for pulmonary drug delivery. The prolonged residence of NPs in the lungs due to ability to escape from the clearance mechanisms such as mucociliary escalator, macrophage uptake (a size of 1-2 µm is ideal for macrophage phagocytosis), and translocation to the systemic circulation is amongst the key advantages of NPs...
2016: Current Pharmaceutical Design
Catherine A Fromen, Tojan B Rahhal, Gregory R Robbins, Marc P Kai, Tammy W Shen, J Christopher Luft, Joseph M DeSimone
UNLABELLED: Engineered nanoparticles have the potential to expand the breadth of pulmonary therapeutics, especially as respiratory vaccines. Notably, cationic nanoparticles have been demonstrated to produce superior local immune responses following pulmonary delivery; however, the cellular mechanisms of this increased response remain unknown. To this end, we investigated the cellular response of lung APCs following pulmonary instillation of anionic and cationic charged nanoparticles. While nanoparticles of both surface charges were capable of trafficking to the draining lymph node and were readily internalized by alveolar macrophages, both CD11b and CD103 lung dendritic cell (DC) subtypes preferentially associated with cationic nanoparticles...
April 2016: Nanomedicine: Nanotechnology, Biology, and Medicine
Gillian S Dean, Derek Clifford, Adam O Whelan, Elma Z Tchilian, Peter C L Beverley, Francisco J Salguero, Zhou Xing, Hans M Vordermeier, Bernardo Villarreal-Ramos
The incidence of bovine tuberculosis (bTB) in the GB has been increasing since the 1980s. Immunisation, alongside current control measures, has been proposed as a sustainable measure to control bTB. Immunisation with Mycobacterium bovis bacillus Calmette-Guerin (BCG) has been shown to protect against bTB. Furthermore, much experimental data indicates that pulmonary local immunity is important for protection against respiratory infections including Mycobacterium tuberculosis and that pulmonary immunisation is highly effective...
2015: PloS One
Mark T Orr, Elyse A Beebe, Thomas E Hudson, David Argilla, Po-Wei D Huang, Valerie A Reese, Christopher B Fox, Steven G Reed, Rhea N Coler
Pulmonary tuberculosis (TB) remains one of the leading causes of infectious disease death despite widespread usage of the BCG vaccine. A number of new TB vaccines have moved into clinical evaluation to replace or boost the BCG vaccine including ID93+GLA-SE, an adjuvanted subunit vaccine. The vast majority of new TB vaccines in trials are delivered parenterally even though intranasal delivery can augment lung-resident immunity and protective efficacy in small animal models. Parenteral immunization with the adjuvanted subunit vaccine ID93+GLA-SE elicits robust TH1 immunity and protection against aerosolized Mycobacterium tuberculosis in mice and guinea pigs...
November 27, 2015: Vaccine
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