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Pulmonary vaccine delivery

Anneliese S Ashhurst, Thaigarajan Parumasivam, John Gar Yan Chan, Leon C W Lin, Manuela Flórido, Nicholas P West, Hak-Kim Chan, Warwick J Britton
Tuberculosis places a staggering burden on human health globally. The new World Health Organisation End-TB Strategy has highlighted the urgent need for more effective TB vaccines to improve control of the disease. Protein-based subunit vaccines offer potential as safe and effective generators of protective immunity, and the use of particulate vaccine formulation and delivery by the pulmonary route may enhance local immunogenicity. In this study, novel particulate subunit vaccines were developed utilising biodegradable poly(lactic-co-glycolic acid) (PLGA) slow-release particles as carriers for the Mycobacterium tuberculosis lipoprotein MPT83, together with the adjuvants trehalose-dibehenate (TDB) or Monophosphoryl lipid A (MPL)...
2018: PloS One
Ka Pang Chan, Deirdre B Fitzgerald, Y C Gary Lee
PURPOSE OF REVIEW: Pleural infection remains an important pulmonary disease, causing significant morbidity and mortality. There is a resurgence of disease burden despite introduction of antibiotics and pneumococcal vaccines. A revisit of the pathogenesis and update on intervention may improve the care of pleural infection. RECENT FINDINGS: Recent studies have uncovered the prognostic implication of the presence of a pleural effusion in patients with pneumonia. Identifying where the bacteria lives may have diagnostic and therapeutic implications...
March 13, 2018: Current Opinion in Pulmonary Medicine
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
Hyejin Kim, Takashi Kimoto, Satoko Sakai, Etsuhisa Takahashi, Hiroshi Kido
We reported previously that intranasal instillation of a synthetic human pulmonary surfactant with a carboxy vinyl polymer as a viscosity improver, named SF-10, shows potent adjuvanticity for humoral immunity in mice and cynomolgus monkeys. SF-10 effectively induces influenza hemagglutinin vaccine (HAv)-specific IgA in nasal and lung washes and IgG in sera with their neutralizing activities. Since CD8+ T cell-mediated protection is an important requirement for adaptive immunity, we investigated in this study the effects of SF-10 with antigen on local and systemic cell-mediated immunity...
2018: PloS One
Pia Steigler, Naomi J Daniels, Tim R McCulloch, Brin M Ryder, Sarah K Sandford, Joanna R Kirman
The tuberculosis (TB) vaccine bacille Calmette-Guérin (BCG) prevents disseminated childhood TB, however fails to protect against the more prevalent pulmonary TB. Limited understanding of the immune response to Mycobacterium tuberculosis, the causative agent of TB, has hindered development of improved vaccines. Although memory CD4 T cells are considered the main mediators of protection against TB, recent studies suggest there are other key subsets that contribute to anti-mycobacterial immunity. To that end, innate cells may be involved in the protective response...
January 9, 2018: Immunology and Cell Biology
Prachi Nangpal, Ritika Kar Bahal, Anil K Tyagi
Tuberculosis (TB) is one of the major causes of mortality all over the globe. BCG, the only vaccine available against this disease has been successful in preventing the severe forms of childhood TB. However, the unsatisfactory performance of BCG in controlling the adult pulmonary tuberculosis has made the development of an effective vaccine against M. tuberculosis a prime objective of the TB research. In this study, a genetically stable, marker-free recombinant MVA expressing α-crystallin of M. tuberculosis (rMVA...
December 11, 2017: Scientific Reports
S Beg, Jaya Agnihotri, Shibhna Singh, Mohammad Wais
Newly developed vaccine VPM1002 confers paradigm swing in the prophylactic treatment of tuberculosis (TB).Multi drug resistant and latent TB in adults as well as in underprivileged patients is instigating menace over world population if the host is immune-compromised. One third of the world's population is infected with TB. Recently it is estimated around 9.6 million people around the world became sick with TB disease. There were 1.5 million TB-related deaths worldwide. Therefore with the advent in biotechnology and Nano engineering, newly adapted survival molecular mechanism of Mycobacterium tuberculosis, new targets receptors on alveolar macrophages must be explored out for eradication of TB from the globe...
December 7, 2017: Recent Patents on Anti-infective Drug Discovery
Arshad Khan, Shailbala Singh, Gloria Galvan, Chinnaswamy Jagannath, K Jagannadha Sastry
Infection by Mycobacterium tuberculosis (Mtb) remains a major global concern and the available Bacillus Calmette-Guerin (BCG) vaccine is poorly efficacious in adults. Therefore, alternative vaccines and delivery strategies focusing on Mtb antigens and appropriate immune stimulating adjuvants are needed to induce protective immunity targeted to the lungs, the primary sites of infections and pathology. We present here evidence in support of mucosal vaccination by the sublingual route in mice using the subunit Mtb antigens Ag85B and ESAT-6 adjuvanted with the glycolipid alpha-galactosylceramide (α-GalCer), a potent natural killer T (NKT) cell agonist...
December 6, 2017: Vaccines
Charles A Specht, Chrono K Lee, Haibin Huang, Maureen M Hester, Jianhua Liu, Bridget A Luckie, Melanie A Torres Santana, Zeynep Mirza, Payam Khoshkenar, Ambily Abraham, Zu T Shen, Jennifer K Lodge, Ali Akalin, Jane Homan, Gary R Ostroff, Stuart M Levitz
Development of a vaccine to protect against cryptococcosis is a priority given the enormous global burden of disease in at-risk individuals. Using glucan particles (GPs) as a delivery system, we previously demonstrated that mice vaccinated with crude Cryptococcus -derived alkaline extracts were protected against lethal challenge with Cryptococcus neoformans and Cryptococcus gattii The goal of the present study was to identify protective protein antigens that could be used in a subunit vaccine. Using biased and unbiased approaches, six candidate antigens (Cda1, Cda2, Cda3, Fpd1, MP88, and Sod1) were selected, recombinantly expressed in Escherichia coli , purified, and loaded into GPs...
November 28, 2017: MBio
Bruce G Weniger, Ian E Anglin, Tina Tong, Michael Pensiero, Jeffrey K Pullen
On May 21st, 2015, the U.S. National Institute of Allergy and Infectious Diseases (NIAID) convened a workshop on delivery devices for nucleic acid (NA) as vaccines in order to review the landscape of past and future technologies for administering NA (e.g., DNA, RNA, etc.) as antigen into target tissues of animal models and humans. Its focus was on current and future applications for preventing and treating human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome (AIDS) disease, among other infectious-disease priorities...
January 25, 2018: Vaccine
Yunfeng Yan, Hu Xiong, Xinyi Zhang, Qiang Cheng, Daniel J Siegwart
Messenger RNA (mRNA) has recently come into focus as an emerging therapeutic class with great potential for protein replacement therapy, cancer immunotherapy, regenerative medicine, vaccines, and gene editing. However, the lack of effective and safe delivery methods impedes the broad application of mRNA-based therapeutics. We report a robust approach to develop efficient polymeric delivery carriers for mRNA. Lead polyesters were identified by in vitro screening of a 480-member combinatorially modified poly(trimethylolpropane allyl ether-co-suberoyl chloride) library for the delivery of luciferase encoding mRNA (Luc mRNA) to IGROV1 cells...
December 11, 2017: Biomacromolecules
Sema Sevimli, Frances C Knight, Pavlo Gilchuk, Sebastian Joyce, John T Wilson
Vaccine design has undergone a shift towards the use of purified protein subunit vaccines, which offer increased safety and greater control over antigen specificity, but at the expense of immunogenicity. Here we report the development of a new polymer-based vaccine delivery platform engineered to enhance immunity through the co-delivery of protein antigens and the Toll-like receptor 7 (TLR7) agonist imiquimod (IMQ). Owing to the preferential solubility of IMQ in fatty acids, a series of block copolymer micelles with a fatty acid-mimetic core comprising lauryl methacrylate (LMA) and methacrylic acid (MAA), and a poly(ethylene glycol) methyl ether methacrylate (PEGMA) corona decorated with pyridyl disulfide ethyl methacrylate (PDSM) moieties for antigen conjugation were synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization...
February 13, 2017: ACS Biomaterials Science & Engineering
Jesse Q Nguyen, Xhavit Zogaj, Aanuoluwa A Adelani, Ping Chu, Jieh-Juen Yu, Bernard P Arulanandam, Karl E Klose
Pulmonary infection with the bacterium Francisella tularensis can lead to the serious and potentially fatal disease, tularemia, in humans. Due to the current lack of an approved tularemia vaccine for humans, research is focused on vaccine development utilizing appropriate animal models. The Fischer 344 rat has emerged as a model that reflects human susceptibility to F. tularensis infection, and thus is an attractive model for tularemia vaccine development. Intratracheal inoculation of the Fischer 344 rat with F...
September 30, 2017: Journal of Visualized Experiments: JoVE
Bahar Barani, Sheeja Rajasingh, Johnson Rajasingh
Cardiovascular diseases are the number one cause of death globally with an estimated 7.4 million people dying from coronary heart disease. Studies have been conducted to identify the therapeutic utility of exosomes in many diseases, including cardiovascular diseases. It has been demonstrated that exosomes are immune modulators, can be used to treat cardiac ischemic injury, pulmonary hypertension and many other diseases, including cancers. Exosomes can be used as a biomarker for disease and cell-free drug delivery system for targeting the cells...
2017: Advances in Experimental Medicine and Biology
Mangalakumari Jeyanathan, Sam Afkhami, Amandeep Khera, Talveer Mandur, Daniela Damjanovic, Yushi Yao, Rocky Lai, Siamak Haddadi, Anna Dvorkin-Gheva, Manel Jordana, Steven L Kunkel, Zhou Xing
Although most novel tuberculosis (TB) vaccines are designed for delivery via the muscle or skin for enhanced protection in the lung, it has remained poorly understood whether systemic vaccine-induced memory T cells can readily home to the lung mucosa prior to and shortly after pathogen exposure. We have investigated this issue by using a model of parenteral TB immunization and intravascular immunostaining. We find that systemically induced memory T cells are restricted to the blood vessels in the lung, unable to populate either the lung parenchymal tissue or the airway under homeostatic conditions...
October 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
Silvia Moreno-Mendieta, Jorge Barrios-Payán, Dulce Mata-Espinosa, Sergio Sánchez, Rogelio Hernández-Pando, Romina Rodríguez-Sanoja
The main challenge for vaccine development or improvement is the lack of safe adjuvants or immunostimulants that induce protective immune responses and can be used for mucosal immunization, which is a highly desirable strategy for vaccination against infectious diseases acquired by oral or intranasal routes. One promising alternative is the use of biodegradable and biocompatible polymeric microparticles. Recently, we developed an immobilization and delivery system with starch microparticles (SMPs) and a starch-binding domain (SBDtag) suitable for the mucosal administration of antigens and the induction of antigen-specific immune responses...
August 14, 2017: Vaccine
Sanjay Mukherjee, Renuka Subramaniam, Han Chen, Anthony Smith, Shiva Keshava, Homayoun Shams
Efferocytosis by alveolar phagocytes (APs) is pivotal in maintenance of lung homeostasis. Increased efferocytosis by APs results in protection against lethal acute lung injury due to pulmonary infections whereas defective efferocytosis by APs results in chronic lung inflammation. In this report, we show that pulmonary delivery of Bacillus Calmette-Guerin (BCG) significantly enhances efferocytosis by APs. Increased efferocytosis by APs maintains lung homeostasis and protects mice against lethal influenza pneumonia...
2017: PloS One
Daniella Calderon-Nieva, Kalhari Bandara Goonewardene, Susantha Gomis, Marianna Foldvari
Veterinary vaccine development has several similarities with human vaccine development to improve the overall health and well-being of species. However, veterinary goals lean more toward feasible large-scale administration methods and low cost to high benefit immunization. Since the respiratory mucosa is easily accessible and most infectious agents begin their infection cycle at the mucosa, immunization through the respiratory route has been a highly attractive vaccine delivery strategy against infectious diseases...
August 2017: Drug Delivery and Translational Research
Kosuke Kataoka, Yoshiko Fukuyama, David E Briles, Tatsuro Miyake, Kohtaro Fujihashi
To develop safe vaccines for inducing mucosal immunity to major pulmonary bacterial infections, appropriate vaccine antigens (Ags), delivery systems and nontoxic molecular adjuvants must be considered. Such vaccine constructs can induce Ag-specific immune responses that protect against mucosal infections. In particular, it has been shown that simply mixing the adjuvant with the bacterial Ag is a relatively easy means of constructing adjuvant-based mucosal vaccine preparations; the resulting vaccines can elicit protective immunity...
June 2017: Microbiology and Immunology
Trevor R F Smith, Katherine Schultheis, Matthew P Morrow, Kimberly A Kraynyak, Jay R McCoy, Kevin C Yim, Karuppiah Muthumani, Laurent Humeau, David B Weiner, Niranjan Y Sardesai, Kate E Broderick
Respiratory syncytial virus (RSV) is a massive medical burden in infants, children and the elderly worldwide, and an effective, safe RSV vaccine remains an unmet need. Here we assess a novel vaccination strategy based on the intradermal delivery of a SynCon® DNA-based vaccine encoding engineered RSV-F antigen using a surface electroporation device (SEP) to target epidermal cells, in clinically relevant experimental models. We demonstrate the ability of this strategy to elicit robust immune responses. Importantly we demonstrate complete resistance to pulmonary infection at a single low dose of vaccine in the cotton rat RSV/A challenge model...
May 15, 2017: Vaccine
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