Developments in the formulation and delivery of spray dried vaccines.

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Kanojia, Gaurav; Have, Rimko Ten; Soema, Peter C; Frijlink, Henderik; Amorij, Jean-Pierre; Kersten, Gideon

2017-10-03

Spray drying is a promising method for the stabilization of vaccines, which are usually formulated as liquids. Usually, vaccine stability is improved by spray drying in the presence of a range of excipients. Unlike freeze drying, there is no freezing step involved, thus the damage related to this step is avoided. The edge of spray drying resides in its ability for particles to be engineered to desired requirements, which can be used in various vaccine delivery methods and routes. Although several spray dried vaccines have shown encouraging preclinical results, the number of vaccines that have been tested in clinical trials is limited, indicating a relatively new area of vaccine stabilization and delivery. This article reviews the current status of spray dried vaccine formulations and delivery methods. In particular it discusses the impact of process stresses on vaccine integrity, the application of excipients in spray drying of vaccines, process and formulation optimization strategies based on Design of Experiment approaches as well as opportunities for future application of spray dried vaccine powders for vaccine delivery.

Developments in the formulation and delivery of spray dried vaccines

Science.gov (United States)

Kanojia, Gaurav; Have, Rimko ten; Soema, Peter C.; Frijlink, Henderik; Amorij, Jean-Pierre; Kersten, Gideon

2017-01-01

ABSTRACT Spray drying is a promising method for the stabilization of vaccines, which are usually formulated as liquids. Usually, vaccine stability is improved by spray drying in the presence of a range of excipients. Unlike freeze drying, there is no freezing step involved, thus the damage related to this step is avoided. The edge of spray drying resides in its ability for particles to be engineered to desired requirements, which can be used in various vaccine delivery methods and routes. Although several spray dried vaccines have shown encouraging preclinical results, the number of vaccines that have been tested in clinical trials is limited, indicating a relatively new area of vaccine stabilization and delivery. This article reviews the current status of spray dried vaccine formulations and delivery methods. In particular it discusses the impact of process stresses on vaccine integrity, the application of excipients in spray drying of vaccines, process and formulation optimization strategies based on Design of Experiment approaches as well as opportunities for future application of spray dried vaccine powders for vaccine delivery. PMID:28925794

Preliminary results from direct-to-facility vaccine deliveries in Kano, Nigeria.

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Aina, Muyi; Igbokwe, Uchenna; Jegede, Leke; Fagge, Rabiu; Thompson, Adam; Mahmoud, Nasir

2017-04-19

As part of its vaccine supply chain redesign efforts, Kano state now pushes vaccines directly from 6 state stores to primary health centers equipped with solar refrigerators. Our objective is to describe preliminary results from the first 20months of Kano's direct vaccine delivery operations. This is a retrospective review of Kano's direct vaccine delivery program. We analyzed trends in health facility vaccine stock levels, and examined the relationship between stock-out rates and each of cascade vaccine deliveries and timeliness of deliveries. Analysis of vaccination trends was based on administrative data from 27 sentinel health facilities. Costs for both the in-sourced and out-sourced approaches were estimated using a bottoms-up model-based approach. Overall stock adequacy increased from 54% in the first delivery cycle to 68% by cycle 33. Conversely, stock-out rates decreased from 41% to 10% over the same period. Similar trends were observed in the out-sourced and in-sourced programs. Stock-out rates rose incrementally with increasing number of cascade facilities, and delays in vaccine deliveries correlated strongly with stock-out rates. Recognizing that stock availability is one of many factors contributing to vaccinations, we nonetheless compared pre- and post- direct deliveries vaccinations in sentinel facilities, and found statistically significant upward trends for 4 out of 6 antigens. 1 antigen (measles) showed an upward trend that was not statistically significant. Hepatitis b vaccinations declined during the period. Overall, there appeared to be a one-year lag between commencement of direct deliveries and the increase in number of vaccinations. Weighted average cost per delivery is US$29.8 and cost per child immunized is US$0.7 per year. Direct vaccine delivery to health facilities in Kano, through a streamlined architecture, has resulted in decreased stock-outs and improved stock adequacy. Concurrent operation of insourced and outsourced programs has

Comparison of vaccine efficacy for different antigen delivery systems for infectious pancreatic necrosis virus vaccines in Atlantic salmon (Salmo salar L.) in a cohabitation challenge model.

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Munang'andu, Hetron M; Fredriksen, Børge N; Mutoloki, Stephen; Brudeseth, Bjørn; Kuo, Tsun-Yung; Marjara, Inderjit S; Dalmo, Roy A; Evensen, Øystein

2012-06-08

Two strains of IPNV made by reverse genetics on the Norwegian Sp strain NVI-015 (GenBank AY379740) backbone encoding the virulent (T(217)A(221)) and avirulent (P(217)T(221)) motifs were used to prepare inactivated whole virus (IWV), nanoparticle vaccines with whole virus, Escherichia coli subunit encoding truncated VP2-TA and VP2-PT, VP2-TA and VP2-PT fusion antigens with putative translocating domains of Pseudomonas aeruginosa exotoxin, and plasmid DNA encoding segment A of the TA strain. Post challenge survival percentages (PCSP) showed that IWV vaccines conferred highest protection (PCSP=42-53) while nanoparticle, sub-unit recombinant and DNA vaccines fell short of the IWV vaccines in Atlantic salmon (Salmo salar L.) postsmolts challenged with the highly virulent Sp strain NVI-015 (TA strain) of IPNV after 560 degree days post vaccination. Antibody levels induced by these vaccines did not show antigenic differences between the virulent and avirulent motifs for vaccines made with the same antigen dose and delivery system after 8 weeks post vaccination. Our findings show that fish vaccinated with less potent vaccines comprising of nanoparticle, DNA and recombinant vaccines got infected much earlier and yielded to higher infection rates than fish vaccinated with IWV vaccines that were highly potent. Ability of the virulent (T(217)A(221)) and avirulent (P(217)T(221)) motifs to limit establishment of infection showed equal protection for vaccines made of the same antigen dose and delivery systems. Prevention of tissue damage linked to viral infection was eminent in the more potent vaccines than the less protective ones. Hence, there still remains the challenge of developing highly efficacious vaccines with the ability to eliminate the post challenge carrier state in IPNV vaccinology. Copyright © 2012 Elsevier Ltd. All rights reserved.

Polyethylenimine-based polyplex delivery of self-replicating RNA vaccines.

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Démoulins, Thomas; Milona, Panagiota; Englezou, Pavlos C; Ebensen, Thomas; Schulze, Kai; Suter, Rolf; Pichon, Chantal; Midoux, Patrick; Guzmán, Carlos A; Ruggli, Nicolas; McCullough, Kenneth C

2016-04-01

Self-amplifying replicon RNA (RepRNA) are large molecules (12-14 kb); their self-replication amplifies mRNA template numbers, affording several rounds of antigen production, effectively increasing vaccine antigen payloads. Their sensitivity to RNase-sensitivity and inefficient uptake by dendritic cells (DCs) - absolute requirements for vaccine design - were tackled by condensing RepRNA into synthetic, nanoparticulate, polyethylenimine (PEI)-polyplex delivery vehicles. Polyplex-delivery formulations for small RNA molecules cannot be transferred to RepRNA due to its greater size and complexity; the N:P charge ratio and impact of RepRNA folding would influence polyplex condensation, post-delivery decompaction and the cytosolic release essential for RepRNA translation. Polyplex-formulations proved successful for delivery of RepRNA encoding influenza virus hemagglutinin and nucleocapsid to DCs. Cytosolic translocation was facilitated, leading to RepRNA translation. This efficacy was confirmed in vivo, inducing both humoral and cellular immune responses. Accordingly, this paper describes the first PEI-polyplexes providing efficient delivery of the complex and large, self-amplifying RepRNA vaccines. The use of self-amplifying replicon RNA (RepRNA) to increase vaccine antigen payloads can potentially be useful in effective vaccine design. Nonetheless, its use is limited by the degradation during the uptake process. Here, the authors attempted to solve this problem by packaging RepRNA using polyethylenimine (PEI)-polyplex delivery vehicles. The efficacy was confirmed in vivo by the appropriate humoral and cellular immune responses. This novel delivery method may prove to be very useful for future vaccine design. Copyright © 2015 Elsevier Inc. All rights reserved.

Self-Amplifying Replicon RNA Vaccine Delivery to Dendritic Cells by Synthetic Nanoparticles

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Kenneth C. McCullough

2014-10-01

Full Text Available Dendritic cells (DC play essential roles determining efficacy of vaccine delivery with respect to immune defence development and regulation. This renders DCs important targets for vaccine delivery, particularly RNA vaccines. While delivery of interfering RNA oligonucleotides to the appropriate intracellular sites for RNA-interference has proven successful, the methodologies are identical for RNA vaccines, which require delivery to RNA translation sites. Delivery of mRNA has benefitted from application of cationic entities; these offer value following endocytosis of RNA, when cationic or amphipathic properties can promote endocytic vesicle membrane perturbation to facilitate cytosolic translocation. The present review presents how such advances are being applied to the delivery of a new form of RNA vaccine, replicons (RepRNA carrying inserted foreign genes of interest encoding vaccine antigens. Approaches have been developed for delivery to DCs, leading to the translation of the RepRNA and encoded vaccine antigens both in vitro and in vivo. Potential mechanisms favouring efficient delivery leading to translation are discussed with respect to the DC endocytic machinery, showing the importance of cytosolic translocation from acidifying endocytic structures. The review relates the DC endocytic pathways to immune response induction, and the potential advantages for these self-replicating RNA vaccines in the near future.

Dissolving Microneedle Arrays for Transdermal Delivery of Amphiphilic Vaccines.

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An, Myunggi; Liu, Haipeng

2017-07-01

Amphiphilic vaccine based on lipid-polymer conjugates is a new type of vaccine capable of self-delivering to the immune system. When injected subcutaneously, amphiphilic vaccines efficiently target antigen presenting cells in the lymph nodes (LNs) via a unique albumin-mediated transport and uptake mechanism and induce potent humoral and cellular immune responses. However, whether this new type of vaccine can be administrated via a safe, convenient microneedle-based transdermal approach remains unstudied. For such skin barrier-disruption systems, a simple application of microneedle arrays (MNs) is desired to disrupt the stratum corneum, and for rapid and pain-free self-administration of vaccines into the skin, the anatomic place permeates with an intricate mesh of lymphatic vessels draining to LNs. Here the microneedle transdermal approach is combined with amphiphilic vaccines to create a simple delivery approach which efficiently traffic molecular vaccines into lymphatics and draining LNs. The rapid release of amphiphilic vaccines into epidermis upon application of dissolving MNs to the skin of mice generates potent cellular and humoral responses, comparable or superior to those elicited by traditional needle-based immunizations. The results suggest that the amphiphilic vaccines delivered by dissolving MNs can provide a simple and safer vaccination method with enhanced vaccine efficacy. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Intranasal and sublingual delivery of inactivated polio vaccine.

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Kraan, Heleen; Soema, Peter; Amorij, Jean-Pierre; Kersten, Gideon

2017-05-09

Polio is on the brink of eradication. Improved inactivated polio vaccines (IPV) are needed towards complete eradication and for the use in the period thereafter. Vaccination via mucosal surfaces has important potential advantages over intramuscular injection using conventional needle and syringe, the currently used delivery method for IPV. One of them is the ability to induce both serum and mucosal immune responses: the latter may provide protection at the port of virus entry. The current study evaluated the possibilities of polio vaccination via mucosal surfaces using IPV based on attenuated Sabin strains. Mice received three immunizations with trivalent sIPV via intramuscular injection, or via the intranasal or sublingual route. The need of an adjuvant for the mucosal routes was investigated as well, by testing sIPV in combination with the mucosal adjuvant cholera toxin. Both intranasal and sublingual sIPV immunization induced systemic polio-specific serum IgG in mice that were functional as measured by poliovirus neutralization. Intranasal administration of sIPV plus adjuvant induced significant higher systemic poliovirus type 3 neutralizing antibody titers than sIPV delivered via the intramuscular route. Moreover, mucosal sIPV delivery elicited polio-specific IgA titers at different mucosal sites (IgA in saliva, fecal extracts and intestinal tissue) and IgA-producing B-cells in the spleen, where conventional intramuscular vaccination was unable to do so. However, it is likely that a mucosal adjuvant is required for sublingual vaccination. Further research on polio vaccination via sublingual mucosal route should include the search for safe and effective adjuvants, and the development of novel oral dosage forms that improve antigen uptake by oral mucosa, thereby increasing vaccine immunogenicity. This study indicates that both the intranasal and sublingual routes might be valuable approaches for use in routine vaccination or outbreak control in the period after

Microneedles for drug and vaccine delivery

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Kim, Yeu-Chun; Park, Jung-Hwan; Prausnitz, Mark R.

2012-01-01

Microneedles were first conceptualized for drug delivery many decades ago, but only became the subject of significant research starting in the mid-1990’s when microfabrication technology enabled their manufacture as (i) solid microneedles for skin pretreatment to increase skin permeability, (ii) microneedles coated with drug that dissolves off in the skin, (iii) polymer microneedles that encapsulate drug and fully dissolve in the skin and (iv) hollow microneedles for drug infusion into the skin. As shown in more than 350 papers now published in the field, microneedles have been used to deliver a broad range of different low molecular weight drugs, biotherapeutics and vaccines, including published human studies with a number of small-molecule and protein drugs and vaccines. Influenza vaccination using a hollow microneedle is in widespread clinical use and a number of solid microneedle products are sold for cosmetic purposes. In addition to applications in the skin, microneedles have also been adapted for delivery of bioactives into the eye and into cells. Successful application of microneedles depends on device function that facilitates microneedle insertion and possible infusion into skin, skin recovery after microneedle removal, and drug stability during manufacturing, storage and delivery, and on patient outcomes, including lack of pain, skin irritation and skin infection, in addition to drug efficacy and safety. Building off a strong technology base and multiple demonstrations of successful drug delivery, microneedles are poised to advance further into clinical practice to enable better pharmaceutical therapies, vaccination and other applications. PMID:22575858

Vaccine vial stopper performance for fractional dose delivery of vaccines.

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Jarrahian, Courtney; Myers, Daniel; Creelman, Ben; Saxon, Eugene; Zehrung, Darin

2017-07-03

Shortages of vaccines such as inactivated poliovirus and yellow fever vaccines have been addressed by administering reduced-or fractional-doses, as recommended by the World Health Organization Strategic Advisory Group of Experts on Immunization, to expand population coverage in countries at risk. We evaluated 3 kinds of vaccine vial stoppers to assess their performance after increased piercing from repeated withdrawal of doses needed when using fractional doses (0.1 mL) from presentations intended for full-dose (0.5 mL) delivery. Self-sealing capacity and fragmentation of the stopper were assessed via modified versions of international standard protocols. All stoppers maintained self-sealing capacity after 100 punctures. The damage to stoppers measured as the fragmentation rate was within the target of ≤ 10% of punctures resulting in a fragment after as many as 50 punctures. We concluded that stopper failure is not likely to be a concern if existing vaccine vials containing up to 10 regular doses are used up to 50 times for fractional dose delivery.

Vaccine delivery system for tuberculosis based on nano-sized hepatitis B virus core protein particles

Directory of Open Access Journals (Sweden)

Dhanasooraj D

2013-02-01

Full Text Available Dhananjayan Dhanasooraj, R Ajay Kumar, Sathish MundayoorMycobacterium Research Group, Rajiv Gandhi Centre for Biotechnology, Kerala, IndiaAbstract: Nano-sized hepatitis B virus core virus-like particles (HBc-VLP are suitable for uptake by antigen-presenting cells. Mycobacterium tuberculosis antigen culture filtrate protein 10 (CFP-10 is an important vaccine candidate against tuberculosis. The purified antigen shows low immune response without adjuvant and tends to have low protective efficacy. The present study is based on the assumption that expression of these proteins on HBc nanoparticles would provide higher protection when compared to the native antigen alone. The cfp-10 gene was expressed as a fusion on the major immunodominant region of HBc-VLP, and the immune response in Balb/c mice was studied and compared to pure proteins, a mixture of antigens, and fusion protein-VLP, all without using any adjuvant. The humoral, cytokine, and splenocyte cell proliferation responses suggested that the HBc-VLP bearing CFP-10 generated an antigen-specific immune response in a Th1-dependent manner. By virtue of its self-adjuvant nature and ability to form nano-sized particles, HBc-VLPs are an excellent vaccine delivery system for use with subunit protein antigens identified in the course of recent vaccine research.Keywords: Mycobacterium tuberculosis, VLP, hepatitis B virus core particle, CFP-10, self-adjuvant, vaccine delivery

Mucosal vaccines: a paradigm shift in the development of mucosal adjuvants and delivery vehicles.

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Srivastava, Atul; Gowda, Devegowda Vishakante; Madhunapantula, SubbaRao V; Shinde, Chetan G; Iyer, Meenakshi

2015-04-01

Mucosal immune responses are the first-line defensive mechanisms against a variety of infections. Therefore, immunizations of mucosal surfaces from which majority of infectious agents make their entry, helps to protect the body against infections. Hence, vaccinization of mucosal surfaces by using mucosal vaccines provides the basis for generating protective immunity both in the mucosal and systemic immune compartments. Mucosal vaccines offer several advantages over parenteral immunization. For example, (i) ease of administration; (ii) non-invasiveness; (iii) high-patient compliance; and (iv) suitability for mass vaccination. Despite these benefits, to date, only very few mucosal vaccines have been developed using whole microorganisms and approved for use in humans. This is due to various challenges associated with the development of an effective mucosal vaccine that can work against a variety of infections, and various problems concerned with the safe delivery of developed vaccine. For instance, protein antigen alone is not just sufficient enough for the optimal delivery of antigen(s) mucosally. Hence, efforts have been made to develop better prophylactic and therapeutic vaccines for improved mucosal Th1 and Th2 immune responses using an efficient and safe immunostimulatory molecule and novel delivery carriers. Therefore, in this review, we have made an attempt to cover the recent advancements in the development of adjuvants and delivery carriers for safe and effective mucosal vaccine production. © 2015 APMIS. Published by John Wiley & Sons Ltd.

Intranasal DNA Vaccine for Protection against Respiratory Infectious Diseases: The Delivery Perspectives

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Yingying Xu

2014-07-01

Full Text Available Intranasal delivery of DNA vaccines has become a popular research area recently. It offers some distinguished advantages over parenteral and other routes of vaccine administration. Nasal mucosa as site of vaccine administration can stimulate respiratory mucosal immunity by interacting with the nasopharyngeal-associated lymphoid tissues (NALT. Different kinds of DNA vaccines are investigated to provide protection against respiratory infectious diseases including tuberculosis, coronavirus, influenza and respiratory syncytial virus (RSV etc. DNA vaccines have several attractive development potential, such as producing cross-protection towards different virus subtypes, enabling the possibility of mass manufacture in a relatively short time and a better safety profile. The biggest obstacle to DNA vaccines is low immunogenicity. One of the approaches to enhance the efficacy of DNA vaccine is to improve DNA delivery efficiency. This review provides insight on the development of intranasal DNA vaccine for respiratory infections, with special attention paid to the strategies to improve the delivery of DNA vaccines using non-viral delivery agents.

Hydrogel nanoparticles and nanocomposites for nasal drug/vaccine delivery.

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Salatin, Sara; Barar, Jaleh; Barzegar-Jalali, Mohammad; Adibkia, Khosro; Milani, Mitra Alami; Jelvehgari, Mitra

2016-09-01

Over the past few years, nasal drug delivery has attracted more and more attentions, and been recognized as the most promising alternative route for the systemic medication of drugs limited to intravenous administration. Many experiments in animal models have shown that nanoscale carriers have the ability to enhance the nasal delivery of peptide/protein drugs and vaccines compared to the conventional drug solution formulations. However, the rapid mucociliary clearance of the drug-loaded nanoparticles can cause a reduction in bioavailability percentage after intranasal administration. Thus, research efforts have considerably been directed towards the development of hydrogel nanosystems which have mucoadhesive properties in order to maximize the residence time, and hence increase the period of contact with the nasal mucosa and enhance the drug absorption. It is most certain that the high viscosity of hydrogel-based nanosystems can efficiently offer this mucoadhesive property. This update review discusses the possible benefits of using hydrogel polymer-based nanoparticles and hydrogel nanocomposites for drug/vaccine delivery through the intranasal administration.

Increase in DNA vaccine efficacy by virosome delivery and co-expression of a cytolytic protein.

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Gargett, Tessa; Grubor-Bauk, Branka; Miller, Darren; Garrod, Tamsin; Yu, Stanley; Wesselingh, Steve; Suhrbier, Andreas; Gowans, Eric J

2014-06-01

The potential of DNA vaccines has not been realised due to suboptimal delivery, poor antigen expression and the lack of localised inflammation, essential for antigen presentation and an effective immune response to the immunogen. Initially, we examined the delivery of a DNA vaccine encoding a model antigen, luciferase (LUC), to the respiratory tract of mice by encapsulation in a virosome. Virosomes that incorporated influenza virus haemagglutinin effectively delivered DNA to cells in the mouse respiratory tract and resulted in antigen expression and systemic and mucosal immune responses to the immunogen after an intranasal (IN) prime/intradermal (ID) boost regimen, whereas a multidose ID regimen only generated systemic immunity. We also examined systemic immune responses to LUC after ID vaccination with a DNA vaccine, which also encoded one of the several cytolytic or toxic proteins. Although the herpes simplex virus thymidine kinase, in the presence of the prodrug, ganciclovir, resulted in cell death, this failed to increase the humoral or cell-mediated immune responses. In contrast, the co-expression of LUC with the rotavirus non-structural protein 4 (NSP4) protein or a mutant form of mouse perforin, proteins which are directly cytolytic, resulted in increased LUC-specific humoral and cell-mediated immunity. On the other hand, co-expression of LUC with diphtheria toxin subunit A or overexpression of perforin or NSP4 resulted in a lower level of immunity. In summary, the efficacy of DNA vaccines can be improved by targeted IN delivery of DNA or by the induction of cell death in vaccine-targeted cells after ID delivery.

STRATEGIES AND PROSPECTS OF NASAL DRUG DELIVERY SYSTEMS

OpenAIRE

Gannu Praveen Kumar

2012-01-01

The recent advancement of nasal drug delivery systems has increased enormously and is gaining significant importance. Intranasal therapy has been an accepted form of treatment in the Ayurvedic system of Indian Medicine. The non-invasive delivery of nasal drug delivery systems made to exploit for the development of successful treatment. The advantages, disadvantages, mechanism of action and application of nasal drug delivery system in local delivery, systematic delivery, nasal vaccines and CNS...

Oral Cholera Vaccination Delivery Cost in Low- and Middle-Income Countries: An Analysis Based on Systematic Review.

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Mogasale, Vittal; Ramani, Enusa; Wee, Hyeseung; Kim, Jerome H

2016-12-01

Use of the oral cholera vaccine (OCV) is a vital short-term strategy to control cholera in endemic areas with poor water and sanitation infrastructure. Identifying, estimating, and categorizing the delivery costs of OCV campaigns are useful in analyzing cost-effectiveness, understanding vaccine affordability, and in planning and decision making by program managers and policy makers. To review and re-estimate oral cholera vaccination program costs and propose a new standardized categorization that can help in collation, analysis, and comparison of delivery costs across countries. Peer reviewed publications listed in PubMed database, Google Scholar and World Health Organization (WHO) websites and unpublished data from organizations involved in oral cholera vaccination. The publications and reports containing oral cholera vaccination delivery costs, conducted in low- and middle-income countries based on World Bank Classification. Limits are humans and publication date before December 31st, 2014. No participants are involved, only costs are collected. Oral cholera vaccination and cost estimation. A systematic review was conducted using pre-defined inclusion and exclusion criteria. Cost items were categorized into four main cost groups: vaccination program preparation, vaccine administration, adverse events following immunization and vaccine procurement; the first three groups constituting the vaccine delivery costs. The costs were re-estimated in 2014 US dollars (US$) and in international dollar (I$). Ten studies were identified and included in the analysis. The vaccine delivery costs ranged from US$0.36 to US$ 6.32 (in US$2014) which was equivalent to I$ 0.99 to I$ 16.81 (in I$2014). The vaccine procurement costs ranged from US$ 0.29 to US$ 29.70 (in US$2014), which was equivalent to I$ 0.72 to I$ 78.96 (in I$2014). The delivery costs in routine immunization systems were lowest from US$ 0.36 (in US$2014) equivalent to I$ 0.99 (in I$2014). The reported cost categories

Development of a Multivalent Subunit Vaccine against Tularemia Using Tobacco Mosaic Virus (TMV Based Delivery System.

Directory of Open Access Journals (Sweden)

Sukalyani Banik

Full Text Available Francisella tularensis is a facultative intracellular pathogen, and is the causative agent of a fatal human disease known as tularemia. F. tularensis is classified as a Category A Biothreat agent by the CDC based on its use in bioweapon programs by several countries in the past and its potential to be used as an agent of bioterrorism. No licensed vaccine is currently available for prevention of tularemia. In this study, we used a novel approach for development of a multivalent subunit vaccine against tularemia by using an efficient tobacco mosaic virus (TMV based delivery platform. The multivalent subunit vaccine was formulated to contain a combination of F. tularensis protective antigens: OmpA-like protein (OmpA, chaperone protein DnaK and lipoprotein Tul4 from the highly virulent F. tularensis SchuS4 strain. Two different vaccine formulations and immunization schedules were used. The immunized mice were challenged with lethal (10xLD100 doses of F. tularensis LVS on day 28 of the primary immunization and observed daily for morbidity and mortality. Results from this study demonstrate that TMV can be used as a carrier for effective delivery of multiple F. tularensis antigens. TMV-conjugate vaccine formulations are safe and multiple doses can be administered without causing any adverse reactions in immunized mice. Immunization with TMV-conjugated F. tularensis proteins induced a strong humoral immune response and protected mice against respiratory challenges with very high doses of F. tularensis LVS. This study provides a proof-of-concept that TMV can serve as a suitable platform for simultaneous delivery of multiple protective antigens of F. tularensis. Refinement of vaccine formulations coupled with TMV-targeting strategies developed in this study will provide a platform for development of an effective tularemia subunit vaccine as well as a vaccination approach that may broadly be applicable to many other bacterial pathogens.

Oral delivery of human biopharmaceuticals, autoantigens and vaccine antigens bioencapsulated in plant cells.

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Kwon, Kwang-Chul; Verma, Dheeraj; Singh, Nameirakpam D; Herzog, Roland; Daniell, Henry

2013-06-15

Among 12billion injections administered annually, unsafe delivery leads to >20million infections and >100million reactions. In an emerging new concept, freeze-dried plant cells (lettuce) expressing vaccine antigens/biopharmaceuticals are protected in the stomach from acids/enzymes but are released to the immune or blood circulatory system when plant cell walls are digested by microbes that colonize the gut. Vaccine antigens bioencapsulated in plant cells upon oral delivery after priming, conferred both mucosal and systemic immunity and protection against bacterial, viral or protozoan pathogens or toxin challenge. Oral delivery of autoantigens was effective against complications of type 1 diabetes and hemophilia, by developing tolerance. Oral delivery of proinsulin or exendin-4 expressed in plant cells regulated blood glucose levels similar to injections. Therefore, this new platform offers a low cost alternative to deliver different therapeutic proteins to combat infectious or inherited diseases by eliminating inactivated pathogens, expensive purification, cold storage/transportation and sterile injections. Copyright © 2012 Elsevier B.V. All rights reserved.

Coated microneedle arrays for transcutaneous delivery of live virus vaccines.

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Vrdoljak, Anto; McGrath, Marie G; Carey, John B; Draper, Simon J; Hill, Adrian V S; O'Mahony, Conor; Crean, Abina M; Moore, Anne C

2012-04-10

Vaccines are sensitive biologics that require continuous refrigerated storage to maintain their viability. The vast majority of vaccines are also administered using needles and syringes. The need for cold chain storage and the significant logistics surrounding needle-and-syringe vaccination is constraining the success of immunization programs. Recombinant live viral vectors are a promising platform for the development of vaccines against a number of infectious diseases, however these viruses must retain infectivity to be effective. Microneedles offer an effective and painless method for delivery of vaccines directly into skin that in the future could provide solutions to current vaccination issues. Here we investigated methods of coating live recombinant adenovirus and modified vaccinia virus Ankara (MVA) vectors onto solid microneedle arrays. An effective spray-coating method, using conventional pharmaceutical processes, was developed, in tandem with suitable sugar-based formulations, which produces arrays with a unique coating of viable virus in a dry form around the shaft of each microneedle on the array. Administration of live virus-coated microneedle arrays successfully resulted in virus delivery, transcutaneous infection and induced an antibody or CD8(+) T cell response in mice that was comparable to that obtained by needle-and-syringe intradermal immunization. To our knowledge, this is the first report of successful vaccination with recombinant live viral vectored vaccines coated on microneedle delivery devices. Copyright © 2011 Elsevier B.V. All rights reserved.

Coated microneedle arrays for transcutaneous delivery of live virus vaccines

Science.gov (United States)

Vrdoljak, Anto; McGrath, Marie G.; Carey, John B.; Draper, Simon J.; Hill, Adrian V.S.; O’Mahony, Conor; Crean, Abina M.; Moore, Anne C.

2016-01-01

Vaccines are sensitive biologics that require continuous refrigerated storage to maintain their viability. The vast majority of vaccines are also administered using needles and syringes. The need for cold chain storage and the significant logistics surrounding needle-and-syringe vaccination is constraining the success of immunization programs. Recombinant live viral vectors are a promising platform for the development of vaccines against a number of infectious diseases, however these viruses must retain infectivity to be effective. Microneedles offer an effective and painless method for delivery of vaccines directly into skin that in the future could provide solutions to current vaccination issues. Here we investigated methods of coating live recombinant adenovirus and modified vaccinia virus Ankara (MVA) vectors onto solid microneedle arrays. An effective spray-coating method, using conventional pharmaceutical processes, was developed, in tandem with suitable sugar-based formulations, which produces arrays with a unique coating of viable virus in a dry form around the shaft of each microneedle on the array. Administration of live virus-coated microneedle arrays successfully resulted in virus delivery, transcutaneous infection and induced an antibody or CD8+ T cell response in mice that was comparable to that obtained by needle-and-syringe intradermal immunization. To our knowledge, this is the first report of successful vaccination with recombinant live viral vectored vaccines coated on microneedle delivery devices. PMID:22245683

Vaccine delivery to disease control: a paradigm shift in health policy.

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John, T Jacob; Jain, Yogesh; Nadimpally, Sarojini; Jesani, Amar

2017-01-01

India's Universal Immunisation Programme (UIP) has resulted in the creation of infrastructure, human resources and systems for the procurement and delivery of vaccines. Recently, new vaccines have been added and there are plans for the introduction of more. However, the outcomes in terms of reduction of the diseases for which the vaccines are being administered remain ambiguous. This is evident from the persistent health issues that children continue to experience, despite immunisation. This situation raises a fundamental ethical question for public health: vaccinations are one of the tools of disease control, but are they properly aligned to the control of disease so as to produce the expected public health utility or benefit?

Oral Cholera Vaccination Delivery Cost in Low- and Middle-Income Countries: An Analysis Based on Systematic Review

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Ramani, Enusa; Wee, Hyeseung; Kim, Jerome H.

2016-01-01

routine immunization systems were lowest from US$ 0.36 (in US$2014) equivalent to I$ 0.99 (in I$2014). Limitations The reported cost categories are not standardized at collection point and may lead to misclassification. Costs for some OCV campaigns are not available and analysis does not include direct and indirect costs to vaccine recipients. Conclusions and implications of key findings Vaccine delivery cost estimation is needed for budgeting and economic analysis of vaccination programs. The cost categorization methodology presented in this study is helpful in collecting OCV delivery costs in a standardized manner, comparing delivery costs, planning vaccination campaigns and informing decision-making. PMID:27930668

A Novel Vaccine Delivery Model of the Apicomplexan Eimeria tenella Expressing Eimeria maxima Antigen Protects Chickens against Infection of the Two Parasites

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Tang, Xinming; Liu, Xianyong; Yin, Guangwen; Suo, Jingxia; Tao, Geru; Zhang, Sixin; Suo, Xun

2018-01-01

Vaccine delivery is critical in antigen discovery and vaccine efficacy and safety. The diversity of infectious diseases in humans and livestock has required the development of varied delivery vehicles to target different pathogens. In livestock animals, previous strategies for the development of coccidiosis vaccines have encountered several hurdles, limiting the development of multiple species vaccine formulations. Here, we describe a novel vaccine delivery system using transgenic Eimeria tenella expressing immunodominant antigens of Eimeria maxima. In this delivery system, the immune mapped protein 1 of E. maxima (EmIMP1) was delivered by the closely related species of E. tenella to the host immune system during the whole endogenous life cycle. The overexpression of the exogenous antigen did not interfere with the reproduction and immunogenicity of transgenic Eimeria. After immunization with the transgenic parasite, we detected EmIMP1’s and E. maxima oocyst antigens’ specific humoral and cellular immune responses. In particular, we observed partial protection of chickens immunized with transgenic E. tenella against subsequent E. maxima infections. Our results demonstrate that the transgenic Eimeria parasite is an ideal coccidia antigen delivery vehicle and represents a new type of coccidiosis vaccines. In addition, this model could potentially be used in the development of malaria live sporozoite vaccines, in which antigens from different strains can be expressed in the vaccine strain. PMID:29375584

A Novel Vaccine Delivery Model of the Apicomplexan Eimeria tenella Expressing Eimeria maxima Antigen Protects Chickens against Infection of the Two Parasites.

Science.gov (United States)

Tang, Xinming; Liu, Xianyong; Yin, Guangwen; Suo, Jingxia; Tao, Geru; Zhang, Sixin; Suo, Xun

2017-01-01

Vaccine delivery is critical in antigen discovery and vaccine efficacy and safety. The diversity of infectious diseases in humans and livestock has required the development of varied delivery vehicles to target different pathogens. In livestock animals, previous strategies for the development of coccidiosis vaccines have encountered several hurdles, limiting the development of multiple species vaccine formulations. Here, we describe a novel vaccine delivery system using transgenic Eimeria tenella expressing immunodominant antigens of Eimeria maxima . In this delivery system, the immune mapped protein 1 of E. maxima (EmIMP1) was delivered by the closely related species of E. tenella to the host immune system during the whole endogenous life cycle. The overexpression of the exogenous antigen did not interfere with the reproduction and immunogenicity of transgenic Eimeria . After immunization with the transgenic parasite, we detected EmIMP1's and E. maxima oocyst antigens' specific humoral and cellular immune responses. In particular, we observed partial protection of chickens immunized with transgenic E. tenella against subsequent E. maxima infections. Our results demonstrate that the transgenic Eimeria parasite is an ideal coccidia antigen delivery vehicle and represents a new type of coccidiosis vaccines. In addition, this model could potentially be used in the development of malaria live sporozoite vaccines, in which antigens from different strains can be expressed in the vaccine strain.

Dissolving and biodegradable microneedle technologies for transdermal sustained delivery of drug and vaccine

Science.gov (United States)

Hong, Xiaoyun; Wei, Liangming; Wu, Fei; Wu, Zaozhan; Chen, Lizhu; Liu, Zhenguo; Yuan, Weien

2013-01-01

Microneedles were first conceptualized for drug delivery many decades ago, overcoming the shortages and preserving the advantages of hypodermic needle and conventional transdermal drug-delivery systems to some extent. Dissolving and biodegradable microneedle technologies have been used for transdermal sustained deliveries of different drugs and vaccines. This review describes microneedle geometry and the representative dissolving and biodegradable microneedle delivery methods via the skin, followed by the fabricating methods. Finally, this review puts forward some perspectives that require further investigation. PMID:24039404

Evaluation of the effects of biodegradable nanoparticles on a vaccine delivery system using AFM, SEM, and TEM.

Science.gov (United States)

Kim, Bum-Gil; Kang, Ik-Joong

2008-09-01

Hepatitis B is a deadly disease, and is carried by 30% of the world's population. Antibodies are produced through a series of three manual vaccinations during infancy and childhood. However, the current needle vaccination not only induces pain in patients, but also can be inconvenient to administer. This is particularly true for the case of newborn babies. Intranasal vaccination is emerging as an alternative parenteral drug delivery method that facilitates drug delivery without causing pain. Chitosan, which is obtained through the deacetylation of chitin from crustacea, is a cationic polymer that is biodegradable, avirulent, and highly absorptive. In this study, ionic gelation between chitosan and TPP was conducted to synthesize chitosan nanoparticles with sizes of 200-400 nm and a surface potential of 55-60 mV, and which can be used as Hepatitis B vaccine carriers. Then, Hepatitis B antigen protein was impregnated to manufacture chitosan-recombinant gene vaccine protein (RGVP) nanoparticles. AFM, SEM, TEM, and STEM were used to analyze the manufactured nanoparticles, whose function as drug carriers and whose usefulness for intranasal vaccination were confirmed through in vivo tests with SD rats.

Chitosan-coated poly(lactic-co-glycolic acid nanoparticles as an efficient delivery system for Newcastle disease virus DNA vaccine

Directory of Open Access Journals (Sweden)

Zhao K

2014-09-01

Full Text Available Kai Zhao,1,* Yang Zhang,1,2,* Xiaoyan Zhang,1,* Ci Shi,1,2 Xin Wang,1 Xiaohua Wang,1 Zheng Jin,3 Shangjin Cui2 1Laboratory of Microbiology, School of Life Science, Heilongjiang University, 2Division of Swine Infectious Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, 3Key Laboratory of Chemical Engineering Process and Technology for High-efficiency Conversion, Heilongjiang University, Harbin, People’s Republic of China *These authors contributed equally to this work Abstract: We determined the efficacy and safety of chitosan (CS-coated poly(lactic-co-glycolic acid (PLGA nanoparticles (NPs as a delivery system for a vaccine to protect chickens against Newcastle disease virus (NDV. The newly constructed vaccine contained DNA (the F gene of NDV. The Newcastle disease virus (NDV F gene deoxyribonucleic acid (DNA plasmid (pFDNA-CS/PLGA-NPs were spherical (diameter =699.1±5.21 nm [mean ± ­standard deviation] and smooth, with an encapsulation efficiency of 98.1% and a Zeta potential of +6.35 mV. An in vitro release assay indicated that CS controlled the burst release of plasmid DNA, such that up to 67.4% of the entire quantity of plasmid DNA was steadily released from the pFDNA-CS/PLGA-NPs. An in vitro expression assay indicated that the expression of nanoparticles (NPs was maintained in the NPs. In an immunization test with specific pathogen-free chickens, the pFDNA-CS/PLGA-NPs induced stronger cellular, humoral, and mucosal immune responses than the plasmid DNA vaccine alone. The pFDNA-CS/PLGA-NPs did not harm 293T cells in an in vitro assay and did not harm chickens in an in vivo assay. Overall, the results indicated that CS-coated PLGA NPs can serve as an efficient and safe mucosal immune delivery system for NDV DNA vaccine.Keywords: mucosal immune delivery system, immune effect

Modified thermoresponsive Poloxamer 407 and chitosan sol-gels as potential sustained-release vaccine delivery systems.

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Kojarunchitt, Thunjiradasiree; Baldursdottir, Stefania; Dong, Yao-Da; Boyd, Ben J; Rades, Thomas; Hook, Sarah

2015-01-01

Thermoresponsive, particle-loaded, Poloxamer 407 (P407)-Pluronic-R® (25R4) or chitosan-methyl cellulose (MC) formulations were developed as single-dose, sustained release vaccines. The sol-gels, loaded either with a particulate vaccine (cubosomes) or soluble antigen (ovalbumin) and adjuvants (Quil A and monophosphoryl lipid A), were free-flowing liquids at room temperature and formed stable gels at physiological temperatures. Rheological results showed that both systems meet the criteria of being thermoresponsive gels. The P407-25R4 sol-gels did not significantly sustain the release of antigen in vivo while the chitosan-MC sol-gels sustained the release of antigen up to at least 14 days after administration. The chitosan-MC sol-gels stimulated both cellular and humoral responses. The inclusion of cubosomes in the sol-gels did not provide a definitive beneficial effect. Further analysis of the formulations with small-angle X-ray scattering (SAXS) revealed that while cubosomes were stable in chitosan-MC gels they were not stable in P407-25R4 formulations. The reason for the mixed response to cubosome-loaded vehicles requires more investigation, however it appears that the cubosomes did not facilitate synchronous vaccine release and may in fact retard release, reducing efficacy in some cases. From these results, chitosan-MC sol-gels show potential as sustained release vaccine delivery systems, as compared to the P407-25R4 system that had a limited ability to sustain antigen release. Copyright © 2014 Elsevier B.V. All rights reserved.

Delivery cost of human papillomavirus vaccination of young adolescent girls in Peru, Uganda and Viet Nam.

Science.gov (United States)

Levin, Carol E; Van Minh, Hoang; Odaga, John; Rout, Swampa Sarit; Ngoc, Diep Nguyen Thi; Menezes, Lysander; Araujo, Maria Ana Mendoza; LaMontagne, D Scott

2013-08-01

To estimate the incremental delivery cost of human papillomavirus (HPV) vaccination of young adolescent girls in Peru, Uganda and Viet Nam. Data were collected from a sample of facilities that participated in five demonstration projects for hpv vaccine delivery: school-based delivery was used in Peru, Uganda and Viet Nam; health-centre-based delivery was also used in Viet Nam; and integrated delivery, which involved existing health services, was also used in Uganda. Microcosting methods were used to guide data collection on the use of resources (i.e. staff, supplies and equipment) and data were obtained from government, demonstration project and health centre administrative records. Delivery costs were expressed in 2009 United States dollars (US$). Exclusively project-related expenses and the cost of the vaccine were excluded. The economic delivery cost per vaccine dose ranged from US$ 1.44 for integrated outreach in Uganda to US$ 3.88 for school-based delivery in Peru. In Viet Nam, the lowest cost per dose was US$ 1.92 for health-centre-based delivery. Cost profiles revealed that, in general, the largest contributing factors were project start-up costs and recurrent personnel costs. The delivery cost of HPV vaccine was higher than published costs for traditional vaccines recommended by the Expanded Programme on Immunization (EPI). The cost of delivering HPV vaccine to young adolescent girls in Peru, Uganda and Viet Nam was higher than that for vaccines currently in the EPI schedule. The cost per vaccine dose was lower when delivery was integrated into existing health services.

Intranasal delivery of nanoparticle-based vaccine increases protection against S. pneumoniae

Energy Technology Data Exchange (ETDEWEB)

Mott, Brittney [University of North Texas Health Science Center, Department of Molecular Biology and Immunology (United States); Thamake, Sanjay [Radio-Isotope Therapy of America Foundation (United States); Vishwanatha, Jamboor; Jones, Harlan P., E-mail: harlan.jones@unthsc.edu [University of North Texas Health Science Center, Department of Molecular Biology and Immunology (United States)

2013-05-15

Nanoparticle (NP) technologies are becoming commonplace in the development of vaccine delivery systems to protect against various diseases. The current study determined the efficacy of intranasal delivery of a 234 {+-} 87.5 nm poly lactic-co-glycolic acid nanoparticle vaccine construct in establishing protection against experimental respiratory pneumococcal infection. Nanoparticles encapsulating heat-killed Streptococcus pneumoniae (NP-HKSP) were retained in the lungs 11 days following nasal administration compared to empty NP. Immunization with NP-HKSP produced significant resistance against S. pneumoniae infection compared to administration of HKSP alone. Increased protection correlated with a significant increase in antigen-specific Th1-associated IFN-{gamma} cytokine response by pulmonary lymphocytes. This study establishes the efficacy of NP-based technology as a non-invasive and targeted approach for nasal-pulmonary immunization against pulmonary infections.

Intranasal delivery of nanoparticle-based vaccine increases protection against S. pneumoniae

International Nuclear Information System (INIS)

Mott, Brittney; Thamake, Sanjay; Vishwanatha, Jamboor; Jones, Harlan P.

2013-01-01

Nanoparticle (NP) technologies are becoming commonplace in the development of vaccine delivery systems to protect against various diseases. The current study determined the efficacy of intranasal delivery of a 234 ± 87.5 nm poly lactic-co-glycolic acid nanoparticle vaccine construct in establishing protection against experimental respiratory pneumococcal infection. Nanoparticles encapsulating heat-killed Streptococcus pneumoniae (NP-HKSP) were retained in the lungs 11 days following nasal administration compared to empty NP. Immunization with NP-HKSP produced significant resistance against S. pneumoniae infection compared to administration of HKSP alone. Increased protection correlated with a significant increase in antigen-specific Th1-associated IFN-γ cytokine response by pulmonary lymphocytes. This study establishes the efficacy of NP-based technology as a non-invasive and targeted approach for nasal-pulmonary immunization against pulmonary infections.

Intranasal delivery of nanoparticle-based vaccine increases protection against S. pneumoniae

Science.gov (United States)

Mott, Brittney; Thamake, Sanjay; Vishwanatha, Jamboor; Jones, Harlan P.

2013-05-01

Nanoparticle (NP) technologies are becoming commonplace in the development of vaccine delivery systems to protect against various diseases. The current study determined the efficacy of intranasal delivery of a 234 ± 87.5 nm poly lactic-co-glycolic acid nanoparticle vaccine construct in establishing protection against experimental respiratory pneumococcal infection. Nanoparticles encapsulating heat-killed Streptococcus pneumoniae (NP-HKSP) were retained in the lungs 11 days following nasal administration compared to empty NP. Immunization with NP-HKSP produced significant resistance against S. pneumoniae infection compared to administration of HKSP alone. Increased protection correlated with a significant increase in antigen-specific Th1-associated IFN-γ cytokine response by pulmonary lymphocytes. This study establishes the efficacy of NP-based technology as a non-invasive and targeted approach for nasal-pulmonary immunization against pulmonary infections.

Stabilization of influenza vaccine enhances protection by microneedle delivery in the mouse skin.

Directory of Open Access Journals (Sweden)

Fu-Shi Quan

2009-09-01

Full Text Available Simple and effective vaccine administration is particularly important for annually recommended influenza vaccination. We hypothesized that vaccine delivery to the skin using a patch containing vaccine-coated microneedles could be an attractive approach to improve influenza vaccination compliance and efficacy.Solid microneedle arrays coated with inactivated influenza vaccine were prepared for simple vaccine delivery to the skin. However, the stability of the influenza vaccine, as measured by hemagglutination activity, was found to be significantly damaged during microneedle coating. The addition of trehalose to the microneedle coating formulation retained hemagglutination activity, indicating stabilization of the coated influenza vaccine. For both intramuscular and microneedle skin immunization, delivery of un-stabilized vaccine yielded weaker protective immune responses including viral neutralizing antibodies, protective efficacies, and recall immune responses to influenza virus. Immunization using un-stabilized vaccine also shifted the pattern of antibody isotypes compared to the stabilized vaccine. Importantly, a single microneedle-based vaccination using stabilized influenza vaccine was found to be superior to intramuscular immunization in controlling virus replication as well as in inducing rapid recall immune responses post challenge.The functional integrity of hemagglutinin is associated with inducing improved protective immunity against influenza. Simple microneedle influenza vaccination in the skin produced superior protection compared to conventional intramuscular immunization. This approach is likely to be applicable to other vaccines too.

Transcutaneous delivery of T Cell-inducing viral vector Malaria vaccines by microneedle patches

OpenAIRE

2011-01-01

There is an urgent need for improvements to existing vaccine delivery technologies to run parallel with the development of new-generation vaccines. The burdens of needle-based immunisation strategies are exacerbated by poor resource provision in such areas as sub-Saharan Africa, where annual malaria mortality stands at 860,000. Needle-free delivery of vaccine to the skin holds promise for improved immunogenicity with lower doses of vaccine, in addition to significant logistical advantages. Va...

Challenges for nationwide vaccine delivery in African countries.

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Songane, Mario

2017-10-19

Vaccines are very effective in providing individual and community (herd) immunity against a range of diseases. In addition to protection against a range of diseases, vaccines also have social and economic benefits. However, for vaccines to be effective, routine immunization programmes must be undertaken regularly to ensure individual and community protection. Nonetheless, in many countries in Africa, vaccination coverage is low because governments struggle to deliver vaccines to the most remote areas, thus contributing to constant outbreaks of various vaccine-preventable diseases. African governments fail to deliver vaccines to a significant percentage of the target population due to many issues in key areas such as policy setting, programme management and financing, supply chain, global vaccine market, research and development of vaccines. This review gives an overview of the causes of these issues and what is currently being done to address them. This review will discuss the role of philanthropic organisations such as the Bill and Melinda Gates Foundation and global partnerships such as the global alliance for vaccines and immunizations in the development, purchase and delivery of vaccines.

Efficacy of thiolated eudragit microspheres as an oral vaccine delivery system to induce mucosal immunity against enterotoxigenic Escherichia coli in mice.

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Lee, Won-Jung; Cha, Seungbin; Shin, Minkyoung; Jung, Myunghwan; Islam, Mohammad Ariful; Cho, Chong-su; Yoo, Han Sang

2012-05-01

A vaccine delivery system based on thiolated eudragit microsphere (TEMS) was studied in vivo for its ability to elicit mucosal immunity against enterotoxigenic Escherichia coli (ETEC). Groups of mice were orally immunized with F4 or F18 fimbriae of ETEC and F4 or F18 loaded in TEMS. Mice that were orally administered with F4 or F18 loaded TEMS showed higher antigen-specific IgG antibody responses in serum and antigen-specific IgA in saliva and feces than mice that were immunized with antigens only. In addition, oral vaccination of F4 or F18 loaded TEMS resulted in higher numbers of IgG and IgA antigen-specific antibody secreting cells in the spleen, lamina propria, and Peyer's patches of immunized mice than other groups. Moreover, TEMS administration loaded with F4 or F18 induced mixed Th1 and Th2 type responses based on similarly increased levels of IgG1 and IgG2a. These results suggest that F4 or F18 loaded TEMS may be a promising candidate for an oral vaccine delivery system to elicit systemic and mucosal immunity against ETEC. Copyright © 2012 Elsevier B.V. All rights reserved.

Veterinary vaccine nanotechnology: pulmonary and nasal delivery in livestock animals.

Science.gov (United States)

Calderon-Nieva, Daniella; Goonewardene, Kalhari Bandara; Gomis, Susantha; Foldvari, Marianna

2017-08-01

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. Additionally, vaccines administered via the respiratory mucosa could lower costs by removing the need of trained medical personnel, and lowering doses yet achieving similar or increased immune stimulation. The respiratory route often brings challenges in antigen delivery efficiency with enough potency to induce immunity. Nanoparticle (NP) technology has been shown to enhance immune activation by producing higher antibody titers and protection. Although specific mechanisms between NPs and biological membranes are still under investigation, physical parameters such as particle size and shape, as well as biological tissue distribution including mucociliary clearance influence the protection and delivery of antigens to the site of action and uptake by target cells. For respiratory delivery, various biomaterials such as mucoadhesive polymers, lipids, and polysaccharides have shown enhanced antibody production or protection in comparison to antigen alone. This review presents promising NPs administered via the nasal or pulmonary routes for veterinary applications specifically focusing on livestock animals including poultry.

Langerin negative dendritic cells promote potent CD8+ T-cell priming by skin delivery of live adenovirus vaccine microneedle arrays.

OpenAIRE

Bachy V; Hervouet C; Becker PD; Chorro L; Carlin LM; Herath S; Papagatsias T; Barbaroux JB; Oh SJ; Benlahrech A; Athanasopoulos T; Dickson G; Patterson S; Kwon SY; Geissmann F

2013-01-01

Stabilization of virus protein structure and nucleic acid integrity is challenging yet essential to preserve the transcriptional competence of live recombinant viral vaccine vectors in the absence of a cold chain. When coupled with needle-free skin delivery, such a platform would address an unmet need in global vaccine coverage against HIV and other global pathogens. Herein, we show that a simple dissolvable microneedle array (MA) delivery system preserves the immunogenicity of vaccines encod...

Estimating the costs of the vaccine supply chain and service delivery for selected districts in Kenya and Tanzania.

Science.gov (United States)

Mvundura, Mercy; Lorenson, Kristina; Chweya, Amos; Kigadye, Rosemary; Bartholomew, Kathryn; Makame, Mohammed; Lennon, T Patrick; Mwangi, Steven; Kirika, Lydia; Kamau, Peter; Otieno, Abner; Murunga, Peninah; Omurwa, Tom; Dafrossa, Lyimo; Kristensen, Debra

2015-05-28

Having data on the costs of the immunization system can provide decision-makers with information to benchmark the costs when evaluating the impact of new technologies or programmatic innovations. This paper estimated the supply chain and immunization service delivery costs and cost per dose in selected districts in Kenya and Tanzania. We also present operational data describing the supply chain and service delivery points (SDPs). To estimate the supply chain costs, we collected resource-use data for the cold chain, distribution system, and health worker time and per diems paid. We also estimated the service delivery costs, which included the time cost of health workers to provide immunization services, and per diems and transport costs for outreach sessions. Data on the annual quantities of vaccines distributed to each facility, and the occurrence and duration of stockouts were collected from stock registers. These data were collected from the national store, 2 regional and 4 district stores, and 12 SDPs in each country for 2012. Cost per dose for the supply chain and immunization service delivery were estimated. The average annual costs per dose at the SDPs were $0.34 (standard deviation (s.d.) $0.18) for Kenya when including only the vaccine supply chain costs, and $1.33 (s.d. $0.82) when including immunization service delivery costs. In Tanzania, these costs were $0.67 (s.d. $0.35) and $2.82 (s.d. $1.64), respectively. Both countries experienced vaccine stockouts in 2012, bacillus Calmette-Guérin vaccine being more likely to be stocked out in Kenya, and oral poliovirus vaccine in Tanzania. When stockouts happened, they usually lasted for at least one month. Tanzania made investments in 2011 in preparation for planned vaccine introductions, and their supply chain cost per dose is expected to decline with the new vaccine introductions. Immunization service delivery costs are a significant portion of the total costs at the SDPs. Copyright © 2015 Elsevier Ltd. All

Anti-cancer vaccination by transdermal delivery of antigen peptide-loaded nanogels via iontophoresis.

Science.gov (United States)

Toyoda, Mao; Hama, Susumu; Ikeda, Yutaka; Nagasaki, Yukio; Kogure, Kentaro

2015-04-10

Transdermal vaccination with cancer antigens is expected to become a useful anti-cancer therapy. However, it is difficult to accumulate enough antigen in the epidermis for effective exposure to Langerhans cells because of diffusion into the skin and muscle. Carriers, such as liposomes and nanoparticles, may be useful for the prevention of antigen diffusion. Iontophoresis, via application of a small electric current, is a noninvasive and efficient technology for transdermal drug delivery. Previously, we succeeded in the iontophoretic transdermal delivery of liposomes encapsulating insulin, and accumulation of polymer-based nanoparticle nanogels in the stratum corneum of the skin. Therefore, in the present study, we examined the use of iontophoresis with cancer antigen gp-100 peptide KVPRNQDWL-loaded nanogels for anti-cancer vaccination. Iontophoresis resulted in the accumulation of gp-100 peptide and nanogels in the epidermis, and subsequent increase in the number of Langerhans cells in the epidermis. Moreover, tumor growth was significantly suppressed by iontophoresis of the antigen peptide-loaded nanogels. Thus, iontophoresis of the antigen peptide-loaded nanogels may serve as an effective transdermal delivery system for anti-cancer vaccination. Copyright © 2015 Elsevier B.V. All rights reserved.

Delivery cost analysis of a reactive mass cholera vaccination campaign: a case study of Shanchol™ vaccine use in Lake Chilwa, Malawi.

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Ilboudo, Patrick G; Le Gargasson, Jean-Bernard

2017-12-19

Cholera is a diarrheal disease that produces rapid dehydration. The infection is a significant cause of mortality and morbidity. Oral cholera vaccine (OCV) has been propagated for the prevention of cholera. Evidence on OCV delivery cost is insufficient in the African context. This study aims to analyze Shanchol vaccine delivery costs, focusing on the vaccination campaign in response of a cholera outbreak in Lake Chilwa, Malawi. The vaccination campaign was implemented in two rounds in February and March 2016. Structured questionnaires were used to collect costs incurred for each vaccination related activity, including vaccine procurement and shipment, training, microplanning, sensitization, social mobilization and vaccination rounds. Costs collected, including financial and economic costs were analyzed using Choltool, a standardized cholera cost calculator. In total, 67,240 persons received two complete doses of the vaccine. Vaccine coverage was higher in the first round than in the second. The two-dose coverage measured with the immunization card was estimated at 58%. The total financial cost incurred in implementing the campaign was US$480275 while the economic cost was US$588637. The total financial and economic costs per fully vaccinated person were US$7.14 and US$8.75, respectively, with delivery costs amounting to US$1.94 and US$3.55, respectively. Vaccine procurement and shipment accounted respectively for 73% and 59% of total financial and economic costs of the total vaccination campaign costs while the incurred personnel cost accounted for 13% and 29% of total financial and economic costs. Cost for delivering a single dose of Shanchol was estimated at US$0.97. This study provides new evidence on economic and financial costs of a reactive campaign implemented by international partners in collaboration with MoH. It shows that involvement of international partners' personnel may represent a substantial share of campaign's costs, affecting unit and vaccine

Thermostable Subunit Vaccines for Pulmonary Delivery: How Close Are We?

DEFF Research Database (Denmark)

Foged, Camilla

2016-01-01

, 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. This review highlights the status and recent advances in formulation and pulmonary delivery of thermostable human subunit vaccines. Such vaccines are very appealing from compliance, distribution and immunological point of view: Being non-invasive, inhalable vaccines are self...... immunity. Here, I review state of the art and perspectives in formulation design and processing methods for powder-based subunit vaccines intended for pulmonary administration, and present dry powder inhaler technologies suitable for translating these vaccines into clinical trials....

Experiences of operational costs of HPV vaccine delivery strategies in Gavi-supported demonstration projects

Science.gov (United States)

Holroyd, Taylor; Nanda, Shreya; Bloem, Paul; Griffiths, Ulla K.; Sidibe, Anissa; Hutubessy, Raymond C. W.

2017-01-01

From 2012 to 2016, Gavi, the Vaccine Alliance, provided support for countries to conduct small-scale demonstration projects for the introduction of the human papillomavirus vaccine, with the aim of determining which human papillomavirus vaccine delivery strategies might be effective and sustainable upon national scale-up. This study reports on the operational costs and cost determinants of different vaccination delivery strategies within these projects across twelve countries using a standardized micro-costing tool. The World Health Organization Cervical Cancer Prevention and Control Costing Tool was used to collect costing data, which were then aggregated and analyzed to assess the costs and cost determinants of vaccination. Across the one-year demonstration projects, the average economic and financial costs per dose amounted to US$19.98 (standard deviation ±12.5) and US$8.74 (standard deviation ±5.8), respectively. The greatest activities representing the greatest share of financial costs were social mobilization at approximately 30% (range, 6–67%) and service delivery at about 25% (range, 3–46%). Districts implemented varying combinations of school-based, facility-based, or outreach delivery strategies and experienced wide variation in vaccine coverage, drop-out rates, and service delivery costs, including transportation costs and per diems. Size of target population, number of students per school, and average length of time to reach an outreach post influenced cost per dose. Although the operational costs from demonstration projects are much higher than those of other routine vaccine immunization programs, findings from our analysis suggest that HPV vaccination operational costs will decrease substantially for national introduction. Vaccination costs may be decreased further by annual vaccination, high initial investment in social mobilization, or introducing/strengthening school health programs. Our analysis shows that drivers of cost are dependent on

Laser facilitates vaccination

Directory of Open Access Journals (Sweden)

Ji Wang

2016-01-01

Full Text Available Development of novel vaccine deliveries and vaccine adjuvants is of great importance to address the dilemma that the vaccine field faces: to improve vaccine efficacy without compromising safety. Harnessing the specific effects of laser on biological systems, a number of novel concepts have been proposed and proved in recent years to facilitate vaccination in a safer and more efficient way. The key advantage of using laser technology in vaccine delivery and adjuvantation is that all processes are initiated by physical effects with no foreign chemicals administered into the body. Here, we review the recent advances in using laser technology to facilitate vaccine delivery and augment vaccine efficacy as well as the underlying mechanisms.

Enhanced Delivery and Potency of Self-Amplifying mRNA Vaccines by Electroporation in Situ

Directory of Open Access Journals (Sweden)

Kaustuv Banerjee

2013-08-01

Full Text Available Nucleic acid-based vaccines such as viral vectors, plasmid DNA (pDNA, and mRNA are being developed as a means to address limitations of both live-attenuated and subunit vaccines. DNA vaccines have been shown to be potent in a wide variety of animal species and several products are now licensed for commercial veterinary but not human use. Electroporation delivery technologies have been shown to improve the generation of T and B cell responses from synthetic DNA vaccines in many animal species and now in humans. However, parallel RNA approaches have lagged due to potential issues of potency and production. Many of the obstacles to mRNA vaccine development have recently been addressed, resulting in a revival in the use of non-amplifying and self-amplifying mRNA for vaccine and gene therapy applications. In this paper, we explore the utility of EP for the in vivo delivery of large, self-amplifying mRNA, as measured by reporter gene expression and immunogenicity of genes encoding HIV envelope protein. These studies demonstrated that EP delivery of self-amplifying mRNA elicited strong and broad immune responses in mice, which were comparable to those induced by EP delivery of pDNA.

Vaccine decision-making begins in pregnancy: Correlation between vaccine concerns, intentions and maternal vaccination with subsequent childhood vaccine uptake.

Science.gov (United States)

Danchin, M H; Costa-Pinto, J; Attwell, K; Willaby, H; Wiley, K; Hoq, M; Leask, J; Perrett, K P; O'Keefe, Jacinta; Giles, M L; Marshall, H

2017-08-12

Maternal and childhood vaccine decision-making begins prenatally. Amongst pregnant Australian women we aimed to ascertain vaccine information received, maternal immunisation uptake and attitudes and concerns regarding childhood vaccination. We also aimed to determine any correlation between a) intentions and concerns regarding childhood vaccination, (b) concerns about pregnancy vaccination, (c) socioeconomic status (SES) and (d) uptake of influenza and pertussis vaccines during pregnancy and routine vaccines during childhood. Women attending public antenatal clinics were recruited in three Australian states. Surveys were completed on iPads. Follow-up phone surveys were done three to six months post delivery, and infant vaccination status obtained via the Australian Childhood Immunisation Register (ACIR). Between October 2015 and March 2016, 975 (82%) of 1184 mothers consented and 406 (42%) agreed to a follow up survey, post delivery. First-time mothers (445; 49%) had significantly more vaccine concerns in pregnancy and only 73% had made a decision about childhood vaccination compared to 89% of mothers with existing children (p-valuepost delivery survey, 46% and 82% of mothers reported receiving pregnancy influenza and pertussis vaccines respectively. The mother's degree of vaccine hesitancy and two attitudinal factors were correlated with vaccine uptake post delivery. There was no association between reported maternal vaccine uptake or SES and childhood vaccine uptake. First time mothers are more vaccine hesitant and undecided about childhood vaccination, and only two thirds of all mothers believed they received enough information during pregnancy. New interventions to improve both education and communication on childhood and maternal vaccines, delivered by midwives and obstetricians in the Australian public hospital system, may reduce vaccine hesitancy for all mothers in pregnancy and post delivery, particularly first-time mothers. Copyright © 2017 Elsevier Ltd

Development of amphiphilic gamma-PGA-nanoparticle based tumor vaccine: potential of the nanoparticulate cytosolic protein delivery carrier.

Science.gov (United States)

Yoshikawa, Tomoaki; Okada, Naoki; Oda, Atsushi; Matsuo, Kazuhiko; Matsuo, Keisuke; Mukai, Yohei; Yoshioka, Yasuo; Akagi, Takami; Akashi, Mitsuru; Nakagawa, Shinsaku

2008-02-08

Nanoscopic therapeutic systems that incorporate biomacromolecules, such as protein and peptides, are emerging as the next generation of nanomedicine aimed at improving the therapeutic efficacy of biomacromolecular drugs. In this study, we report that poly(gamma-glutamic acid)-based nanoparticles (gamma-PGA NPs) are excellent protein delivery carriers for tumor vaccines that delivered antigenic proteins to antigen-presenting cells and elicited potent immune responses. Importantly, gamma-PGA NPs efficiently delivered entrapped antigenic proteins through cytosolic translocation from the endosomes, which is a key process of gamma-PGA NP-mediated anti-tumor immune responses. Our findings suggest that the gamma-PGA NP system is suitable for the intracellular delivery of protein-based drugs as well as tumor vaccines.

Microneedle-based drug and vaccine delivery via nanoporous microneedle arrays

OpenAIRE

Maaden, van der, Koen; Lüttge, R Regina; Vos, PJW; Bouwstra, Joke A; Kersten, Gideon FA; Ploemen, IHJ Ingmar

2015-01-01

In the literature, several types of microneedles have been extensively described. However, porous microneedle arrays only received minimal attention. Hence, only little is known about drug delivery via these microneedles. However, porous microneedle arrays may have potential for future microneedle-based drug and vaccine delivery and could be a valuable addition to the other microneedle-based drug delivery approaches. To gain more insight into porous microneedle technologies, the scientific an...

The imperative for stronger vaccine supply and logistics systems.

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Zaffran, Michel; Vandelaer, Jos; Kristensen, Debra; Melgaard, Bjørn; Yadav, Prashant; Antwi-Agyei, K O; Lasher, Heidi

2013-04-18

With the introduction of new vaccines, developing countries are facing serious challenges in their vaccine supply and logistics systems. Storage capacity bottlenecks occur at national, regional, and district levels and system inefficiencies threaten vaccine access, availability, and quality. As countries adopt newer and more expensive vaccines and attempt to reach people at different ages and in new settings, their logistics systems must be strengthened and optimized. As a first step, national governments, donors, and international agencies have crafted a global vision for 2020 vaccine supply and logistics systems with detailed plans of action to achieve five priority objectives. Vaccine products and packaging are designed to meet the needs of developing countries. Immunization supply systems support efficient and effective vaccine delivery. The environmental impact of energy, materials, and processes used in immunization systems is minimized. Immunization information systems enable better and more timely decision-making. Competent and motivated personnel are empowered to handle immunization supply chain issues. Over the next decade, vaccine supply and logistics systems in nearly all developing countries will require significant investments of time and resources from global and national partners, donors, and governments. These investments are critical if we are to reach more people with current and newer vaccines. Copyright © 2012 Elsevier Ltd. All rights reserved.

Engineering Microneedle Patches for Vaccination and Drug Delivery to Skin.

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Prausnitz, Mark R

2017-06-07

Microneedle patches (MNPs) contain arrays of solid needles measuring hundreds of microns in length that deliver drugs and vaccines into skin in a painless, easy-to-use manner. Optimal MNP design balances multiple interdependent parameters that determine mechanical strength, skin-insertion reliability, drug delivery efficiency, painlessness, manufacturability, and other features of MNPs that affect their performance. MNPs can be made by adapting various microfabrication technologies for delivery of small-molecule drugs, biologics, and vaccines targeted to the skin, which can have pharmacokinetic and immunologic advantages. A small number of human clinical trials, as well as a large and growing market for MNP products for cosmetics, indicate that MNPs can be used safely, efficaciously, and with strong patient acceptance. More advanced clinical trials and commercial-scale manufacturing will facilitate development of MNPs to realize their potential to dramatically increase patient access to otherwise-injectable drugs and to improve drug performance via skin delivery.

Vial usage, device dead space, vaccine wastage, and dose accuracy of intradermal delivery devices for inactivated poliovirus vaccine (IPV).

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Jarrahian, Courtney; Rein-Weston, Annie; Saxon, Gene; Creelman, Ben; Kachmarik, Greg; Anand, Abhijeet; Zehrung, Darin

2017-03-27

Intradermal delivery of a fractional dose of inactivated poliovirus vaccine (IPV) offers potential benefits compared to intramuscular (IM) delivery, including possible cost reductions and easing of IPV supply shortages. Objectives of this study were to assess intradermal delivery devices for dead space, wastage generated by the filling process, dose accuracy, and total number of doses that can be delivered per vial. Devices tested included syringes with staked (fixed) needles (autodisable syringes and syringes used with intradermal adapters), a luer-slip needle and syringe, a mini-needle syringe, a hollow microneedle device, and disposable-syringe jet injectors with their associated filling adapters. Each device was used to withdraw 0.1-mL fractional doses from single-dose IM glass vials which were then ejected into a beaker. Both vial and device were weighed before and after filling and again after expulsion of liquid to record change in volume at each stage of the process. Data were used to calculate the number of doses that could potentially be obtained from multidose vials. Results show wide variability in dead space, dose accuracy, overall wastage, and total number of doses that can be obtained per vial among intradermal delivery devices. Syringes with staked needles had relatively low dead space and low overall wastage, and could achieve a greater number of doses per vial compared to syringes with a detachable luer-slip needle. Of the disposable-syringe jet injectors tested, one was comparable to syringes with staked needles. If intradermal delivery of IPV is introduced, selection of an intradermal delivery device can have a substantial impact on vaccine wasted during administration, and thus on the required quantity of vaccine that needs to be purchased. An ideal intradermal delivery device should be not only safe, reliable, accurate, and acceptable to users and vaccine recipients, but should also have low dead space, high dose accuracy, and low overall

Transdermal drug delivery

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Prausnitz, Mark R.; Langer, Robert

2009-01-01

Transdermal drug delivery has made an important contribution to medical practice, but has yet to fully achieve its potential as an alternative to oral delivery and hypodermic injections. First-generation transdermal delivery systems have continued their steady increase in clinical use for delivery of small, lipophilic, low-dose drugs. Second-generation delivery systems using chemical enhancers, non-cavitational ultrasound and iontophoresis have also resulted in clinical products; the ability of iontophoresis to control delivery rates in real time provides added functionality. Third-generation delivery systems target their effects to skin’s barrier layer of stratum corneum using microneedles, thermal ablation, microdermabrasion, electroporation and cavitational ultrasound. Microneedles and thermal ablation are currently progressing through clinical trials for delivery of macromolecules and vaccines, such as insulin, parathyroid hormone and influenza vaccine. Using these novel second- and third-generation enhancement strategies, transdermal delivery is poised to significantly increase impact on medicine. PMID:18997767

DNA vaccination for cervical cancer: Strategic optimisation of RALA mediated gene delivery from a biodegradable microneedle system.

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Cole, Grace; Ali, Ahlam A; McCrudden, Cian M; McBride, John W; McCaffrey, Joanne; Robson, Tracy; Kett, Vicky L; Dunne, Nicholas J; Donnelly, Ryan F; McCarthy, Helen O

2018-03-03

Dissolvable microneedles can be employed to deliver DNA to antigen presenting cells within the skin. However, this technology faces two main challenges: the poor transfection efficacy of pDNA following release from the microneedle matrix, and the limited loading capacity of the micron-scale devices. Two-tier delivery systems combining microneedle platforms and DNA delivery vectors have increased efficacy but the challenge of increasing the loading capacity remains. This study utilised lyophilisation to increase the loading of RALA/pDNA nanoparticles within dissolvable PVA microneedles. As a result, delivery was significantly enhanced in vivo into an appropriate range for DNA vaccination (∼50 μg per array). Furthermore, modifying the manufacturing process was not detrimental to the microneedle mechanical properties or cargo functionality. It was demonstrated that arrays retained mechanical and functional stability over short term storage, and were able to elicit gene expression in vitro and in vivo. Finally, treatment with this novel formulation significantly retarded the growth of established tumours, and proved superior to standard intramuscular injection in a preclinical model of cervical cancer. Copyright © 2018. Published by Elsevier B.V.

Microneedle-based drug and vaccine delivery via nanoporous microneedle arrays.

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van der Maaden, Koen; Luttge, Regina; Vos, Pieter Jan; Bouwstra, Joke; Kersten, Gideon; Ploemen, Ivo

2015-08-01

In the literature, several types of microneedles have been extensively described. However, porous microneedle arrays only received minimal attention. Hence, only little is known about drug delivery via these microneedles. However, porous microneedle arrays may have potential for future microneedle-based drug and vaccine delivery and could be a valuable addition to the other microneedle-based drug delivery approaches. To gain more insight into porous microneedle technologies, the scientific and patent literature is reviewed, and we focus on the possibilities and constraints of porous microneedle technologies for dermal drug delivery. Furthermore, we show preliminary data with commercially available porous microneedles and describe future directions in this field of research.

Tattoo Delivery of a Semliki Forest Virus-Based Vaccine Encoding Human Papillomavirus E6 and E7

NARCIS (Netherlands)

van de Wall, Stephanie; Walczak, Mateusz; van Rooij, Nienke; Hoogeboom, Baukje-Nynke; Meijerhof, Tjarko; Nijman, Hans W; Daemen, Toos

2015-01-01

The skin is an attractive organ for immunization because of the presence of antigen-presenting cells. Intradermal delivery via tattooing has demonstrated superior vaccine immunogenicity of DNA vaccines in comparison to conventional delivery methods. In this study, we explored the efficacy of tattoo

Future of human Chlamydia vaccine: potential of self-adjuvanting biodegradable nanoparticles as safe vaccine delivery vehicles.

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Sahu, Rajnish; Verma, Richa; Dixit, Saurabh; Igietseme, Joseph U; Black, Carolyn M; Duncan, Skyla; Singh, Shree R; Dennis, Vida A

2018-03-01

There is a persisting global burden and considerable public health challenge by the plethora of ocular, genital and respiratory diseases caused by members of the Gram-negative bacteria of the genus Chlamydia. The major diseases are conjunctivitis and blinding trachoma, non-gonococcal urethritis, cervicitis, pelvic inflammatory disease, ectopic pregnancy, tubal factor infertility, and interstitial pneumonia. The failures in screening and other prevention programs led to the current medical opinion that an efficacious prophylactic vaccine is the best approach to protect humans from chlamydial infections. Unfortunately, there is no human Chlamydia vaccine despite successful veterinary vaccines. A major challenge has been the effective delivery of vaccine antigens to induce safe and effective immune effectors to confer long-term protective immunity. The dawn of the era of biodegradable polymeric nanoparticles and the adjuvanted derivatives may accelerate the realization of the dream of human vaccine in the foreseeable future. Areas covered: This review focuses on the current status of human chlamydial vaccine research, specifically the potential of biodegradable polymeric nanovaccines to provide efficacious Chlamydia vaccines in the near future. Expert commentary: The safety of biodegradable polymeric nanoparticles-based experimental vaccines with or without adjuvants and the array of available chlamydial vaccine candidates would suggest that clinical trials in humans may be imminent. Also, the promising results from vaccine testing in animal models could lead to human vaccines against trachoma and reproductive diseases simultaneously.

Development of novel double-decker microneedle patches for transcutaneous vaccine delivery.

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Ono, Akihiko; Azukizawa, Hiroaki; Ito, Sayami; Nakamura, Yuki; Asada, Hideo; Quan, Ying-Shu; Kamiyama, Fumio; Katayama, Ichiro; Hirobe, Sachiko; Okada, Naoki

2017-10-30

Microneedle (MN) patches have great potential as transcutaneous vaccine delivery devices because MNs can effectively deliver vaccine antigen into the skin through the micropores formed in the stratum corneum by low-invasive and painless skin puncturing. This study aims to develop novel double-decker MN patches which have not only high safety and efficacy but also broad applicability to various vaccine antigens. We developed two types of MN patches (PGA-MN and Nylon-MN) that are made from polyglycolic acid and Nylon-6. In pre-clinical studies, both MN patches could demonstrably deliver antigens into resected human dermal tissue, prolong antigen deposition and increase antigen-specific IgG levels after vaccination compared with conventional injections. We demonstrated both MN patches could be safely applied to human skin because no broken MNs or significant skin irritation were observed after applications in the clinical research. PGA-MN was suggested to be superior to Nylon-MN regarding human skin puncturability based on measurements of transepidermal water loss and needle failure force. A high content of tetravalent influenza hemagglutinin antigens loaded on PGA-MN could stably maintain HA titers at 35°C for 1year. Overall, double-decker MN patches can reliably and safely puncture human skin and are promising as effective transcutaneous vaccine delivery devices. Copyright © 2017 Elsevier B.V. All rights reserved.

Induction of a robust immune response against avian influenza virus following transdermal inoculation with H5-DNA vaccine formulated in modified dendrimer-based delivery system in mouse model.

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Bahadoran, Azadeh; Ebrahimi, Mehdi; Yeap, Swee Keong; Safi, Nikoo; Moeini, Hassan; Hair-Bejo, Mohd; Hussein, Mohd Zobir; Omar, Abdul Rahman

2017-01-01

This study was aimed to evaluate the immunogenicity of recombinant plasmid deoxyribonucleic acid (DNA), pBud-H5-green fluorescent protein (GFP)-interferon-regulatory factor (IRF)3 following delivery using polyamidoamine (PAMAM) dendrimer and transactivator of transcription (TAT)-conjugated PAMAM dendrimer as well as the effect of IRF3 as the genetic adjuvant. BALB/c mice were vaccinated transdermally with pBud-H5-GFP, PAMAM/pBud-H5-GFP, TAT-PAMAM/pBud-H5-GFP, and TAT-PAMAM/pBud-H5-GFP-IRF3. The expression analysis of H5 gene from the blood by using quantitative real-time reverse transcriptase polymerase chain reaction confirmed the ability of PAMAM dendrimer as a carrier for gene delivery, as well as the ability of TAT peptide to enhance the delivery efficiency of PAMAM dendrimer. Mice immunized with modified PAMAM by TAT peptide showed higher hemagglutination inhibition titer, and larger CD3 + /CD4 + T cells and CD3 + /CD8 + T cells population, as well as the production of cytokines, namely, interferon (IFN)-γ, interleukin (IL)-2, IL-15, IL-12, IL-6, and tumor necrosis factor-α compared with those immunized with native PAMAM. These results suggest that the function of TAT peptide as a cell-penetrating peptide is able to enhance the gene delivery, which results in rapid distribution of H5 in the tissues of the immunized mice. Furthermore, pBud-H5-GFP co-expressing IRF3 as a genetic adjuvant demonstrated the highest hemagglutination inhibition titer besides larger CD3 + /CD4 + and CD3 + /CD8 + T cells population, and strong Th1-like cytokine responses among all the systems tested. In conclusion, TAT-PAMAM dendrimer-based delivery system with IRF3 as a genetic adjuvant is an attractive transdermal DNA vaccine delivery system utilized to evaluate the efficacy of the developed DNA vaccine in inducing protection during challenge with virulent H5N1 virus.

Development of Tat-Conjugated Dendrimer for Transdermal DNA Vaccine Delivery.

Science.gov (United States)

Bahadoran, Azadeh; Moeini, Hassan; Bejo, Mohd Hair; Hussein, Mohd Zobir; Omar, Abdul Rahman

In order to enhance cellular uptake and to facilitate transdermal delivery of DNA vaccine, polyamidoamine (PAMAM) dendrimers conjugated with HIV transactivator of transcription (TAT) was developed. First, the plasmid DNA (pIRES-H5/GFP) nanoparticle was formulated using PAMAM dendrimer and TAT peptide and then characterized for surface charge, particle size, DNA encapsulation and protection of the pIRES-H5/GFP DNA plasmid to enzymatic digestion. Subsequently, the potency of the TAT-conjugated dendrimer for gene delivery was evaluated through in vitro transfection into Vero cells followed by gene expression analysis including western blotting, fluorescent microscopy and PCR. The effect of the TAT peptide on cellular uptake of DNA vaccine was studied by qRT-PCR and flow cytometry. Finally, the ability of TAT-conjugated PAMAM dendrimer for transdermal delivery of the DNA plasmid was assessed through artificial membranes followed by qRT-PCR and flow cytometry. TAT-conjugated PAMAM dendrimer showed the ability to form a compact and nanometre-sized polyplexes with the plasmid DNA, having the size range of 105 to 115 nm and a positive charge of +42 to +45 mV over the N/P ratio of 6:1(+/-).  In vitro transfection analysis into Vero cells confirms the high potency of TAT-conjugated PAMAM dendrimer to enhance the cellular uptake of DNA vaccine.  The permeability value assay through artificial membranes reveals that TAT-conjugated PAMAM has more capacity for transdermal delivery of the DNA compared to unmodified PAMAM dendrimer (Pdendrimer is a promising non-viral vector for transdermal use.This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

Enhanced immunization via dissolving microneedle array-based delivery system incorporating subunit vaccine and saponin adjuvant

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Zhao JH

2017-07-01

Full Text Available Ji-Hui Zhao,1,* Qi-Bo Zhang,1,* Bao Liu,2 Xiang-Hua Piao,1 Yu-Lu Yan,1 Xiao-Ge Hu,1 Kuan Zhou,1 Yong-Tai Zhang,1 Nian-Ping Feng1 1School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Anethesiology Department, Augusta University, Augusta, GA, USA *These authors contributed equally to this work Purpose: To enhance the immunogenicity of the model subunit vaccine, ovalbumin (OVA was combined with platycodin (PD, a saponin adjuvant. To reduce the toxicity of PD, OVA, and adjuvant were loaded together into liposomes before being incorporated into a dissolving microneedle array.Methods: OVA- and PD-loaded liposomes (OVA-PD-Lipos were prepared using the film dispersion method. Their uptake behavior, toxicity to mouse bone marrow dendritic cells (BMDCs, and hemolytic activity to rabbit red blood cells (RBCs were evaluated. The OVA-PD-Lipos were incorporated into a dissolving microneedle array. The chemical stability of OVA and the physical stability of OVA-PD-Lipos in microneedle arrays were investigated. The immune response of Institute of Cancer Research mice and potential skin irritation reaction of rabbits to OVA-PD-Lipos-MNs were evaluated.Results: The uptake of OVA by mouse BMDCs was greatly enhanced when OVA was prepared as OVA-PD-Lipos, and in this form, the toxicity of PD was dramatically reduced. OVA was chemically stable as OVA-PD-Lipos, when OVA-PD-Lipos was incorporated into a dissolving microneedle array. Institute of Cancer Research mice treated with OVA-PD-Lipos-MNs showed a significantly enhanced immune response. PD combined with OVA elicited a balanced Th1 and Th2 humoral immune response in mice, with minimal irritation in rabbit skin.Conclusion: The dissolving microneedle array-based system is a promising delivery vehicle for subunit vaccine and its adjuvant. Keywords: subunit vaccine, saponin adjuvant, liposomes, dissolving microneedle array, intradermal vaccination

Dissolving and biodegradable microneedle technologies for transdermal sustained delivery of drug and vaccine

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Hong X

2013-09-01

Full Text Available Xiaoyun Hong,1,2,* Liangming Wei,3,* Fei Wu,2,* Zaozhan Wu,2 Lizhu Chen,2 Zhenguo Liu,1 Weien Yuan2 1Department of Neurology, Xinhua Hospital, Shanghai, People's Republic of China; 2School of Pharmacy, Shanghai JiaoTong University, Shanghai, People's Republic of China; 3Research Institute of Micro/Nano Science and Technology, Shanghai JiaoTong University, Shanghai, People's Republic of China *These authors contributed equally to this work Abstract: Microneedles were first conceptualized for drug delivery many decades ago, overcoming the shortages and preserving the advantages of hypodermic needle and conventional transdermal drug-delivery systems to some extent. Dissolving and biodegradable microneedle technologies have been used for transdermal sustained deliveries of different drugs and vaccines. This review describes microneedle geometry and the representative dissolving and biodegradable microneedle delivery methods via the skin, followed by the fabricating methods. Finally, this review puts forward some perspectives that require further investigation. Keywords: microneedle, dissolving, biodegradable, sustained release

Development and characterization of a new carrier for vaccine delivery based on calcium-alginate nanoparticles: Safe immunoprotective approach against scorpion envenoming.

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Nait Mohamed, Faez Amokrane; Laraba-Djebari, Fatima

2016-05-23

To enhance humoral defense against diseases, vaccine formulation is routinely prepared to improve immune response. Studies in nanomaterials as a carrier of vaccine delivery are promising and interesting. In this study, attenuated Androctonus australis hector (Aah) venom and its toxic fraction were encapsulated into different formulations inside calcium-alginate nanoparticles (Ca-Alg Nps), and used as a vaccine delivery system against scorpion envenomation. Ca-Alg Nps were prepared by ionic gelation and characterized. An immunization schedule was undertaken in rabbits in order to study how Aah venom entrapped in Ca-Alg Nps might induce protective immunity. Results showed the influence of different parameters on the suitable nanoparticle formation. They also showed no toxicity of free Ca-Alg Nps and a different inflammatory profile depending on the nanovaccine formulations. More interestingly, evaluation of specific IgG titer and IgG1/IgG2a isotype balance revealed a protective effect with the nanoparticles encapsulating the attenuated antigens. Challenge up to 6 LD 50 of native venom, allowed to an important immunoprotection of all immunized rabbits, with no recorded death. Taken together and with respect to the properties of nanoparticles and high immunogenicity, calcium-alginate nanoparticles could be considered as a new promising adjuvant system and a vaccine delivery against scorpion envenomation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Nanotechnology and vaccine development

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Mi-Gyeong Kim

2014-10-01

Full Text Available Despite the progress of conventional vaccines, improvements are clearly required due to concerns about the weak immunogenicity of these vaccines, intrinsic instability in vivo, toxicity, and the need for multiple administrations. To overcome such problems, nanotechnology platforms have recently been incorporated into vaccine development. Nanocarrier-based delivery systems offer an opportunity to enhance the humoral and cellular immune responses. This advantage is attributable to the nanoscale particle size, which facilitates uptake by phagocytic cells, the gut-associated lymphoid tissue, and the mucosa-associated lymphoid tissue, leading to efficient antigen recognition and presentation. Modifying the surfaces of nanocarriers with a variety of targeting moieties permits the delivery of antigens to specific cell surface receptors, thereby stimulating specific and selective immune responses. In this review, we introduce recent advances in nanocarrier-based vaccine delivery systems, with a focus on the types of carriers, including liposomes, emulsions, polymer-based particles, and carbon-based nanomaterials. We describe the remaining challenges and possible breakthroughs, including the development of needle-free nanotechnologies and a fundamental understanding of the in vivo behavior and stability of the nanocarriers in nanotechnology-based delivery systems.

Characterization of guinea pig T cell responses elicited after EP-assisted delivery of DNA vaccines to the skin.

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Schultheis, Katherine; Schaefer, Hubert; Yung, Bryan S; Oh, Janet; Muthumani, Karuppiah; Humeau, Laurent; Broderick, Kate E; Smith, Trevor R F

2017-01-03

The skin is an ideal target tissue for vaccine delivery for a number of reasons. It is highly accessible, and most importantly, enriched in professional antigen presenting cells. Possessing strong similarities to human skin physiology and displaying a defined epidermis, the guinea pig is an appropriate model to study epidermal delivery of vaccine. However, whilst we have characterized the humoral responses in the guinea pig associated with skin vaccine protocols we have yet to investigate the T cell responses. In response to this inadequacy, we developed an IFN-γ ELISpot assay to characterize the cellular immune response in the peripheral blood of guinea pigs. Using a nucleoprotein (NP) influenza pDNA vaccination regimen, we characterized host T cell responses. After delivery of the DNA vaccine to the guinea pig epidermis we detected robust and rapid T cell responses. The levels of IFN-γ spot-forming units averaged approximately 5000 per million cells after two immunizations. These responses were broad in that multiple regions across the NP antigen elicited a T cell response. Interestingly, we identified a number of NP immunodominant T cell epitopes to be conserved across an outbred guinea pig population, a phenomenon which was also observed after immunization with a RSV DNA vaccine. We believe this data enhances our understanding of the cellular immune response elicited to a vaccine in guinea pigs, and globally, will advance the use of this model for vaccine development, especially those targeting skin as a delivery site. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Intranasal delivery of a bivalent norovirus vaccine formulated in an in situ gelling dry powder.

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Jordan P Ball

Full Text Available The global health community is beginning to understand the burden of norovirus-associated disease, which has a significant impact in both developed and developing countries. Norovirus virus like particle (VLP-based vaccines are currently under development and have been shown to elicit systemic and mucosal immune responses when delivered intranasally. In the present study, we describe the use of a dry powder formulation (GelVac™ with an in situ gelling polysaccharide (GelSite™ extracted from Aloe vera for nasal delivery of a bivalent vaccine formulation containing both GI and GII.4 norovirus VLPs. Dose-ranging studies were performed to identify the optimal antigen dosages based on systemic and mucosal immune responses in guinea pigs and determine any antigenic interference. A dose-dependent increase in systemic and mucosal immunogenicity against each of the VLPs were observed as well as a boosting effect for each VLP after the second dosing. A total antigen dose of ≥50 μg of each GI and GII.4 VLPs was determined to be the maximally immunogenic dose in guinea pigs. The immunogenicity results of this bivalent formulation, taken together with previous work on monovalent GelVac™ norovirus vaccine formulation, provides a basis for future development of this norovirus VLP vaccine.

A case study using the United Republic of Tanzania: costing nationwide HPV vaccine delivery using the WHO Cervical Cancer Prevention and Control Costing Tool

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Hutubessy Raymond

2012-11-01

Full Text Available Abstract Background The purpose, methods, data sources and assumptions behind the World Health Organization (WHO Cervical Cancer Prevention and Control Costing (C4P tool that was developed to assist low- and middle-income countries (LMICs with planning and costing their nationwide human papillomavirus (HPV vaccination program are presented. Tanzania is presented as a case study where the WHO C4P tool was used to cost and plan the roll-out of HPV vaccines nationwide as part of the national comprehensive cervical cancer prevention and control strategy. Methods The WHO C4P tool focuses on estimating the incremental costs to the health system of vaccinating adolescent girls through school-, health facility- and/or outreach-based strategies. No costs to the user (school girls, parents or caregivers are included. Both financial (or costs to the Ministry of Health and economic costs are estimated. The cost components for service delivery include training, vaccination (health personnel time and transport, stationery for tally sheets and vaccination cards, and so on, social mobilization/IEC (information, education and communication, supervision, and monitoring and evaluation (M&E. The costs of all the resources used for HPV vaccination are totaled and shown with and without the estimated cost of the vaccine. The total cost is also divided by the number of doses administered and number of fully immunized girls (FIGs to estimate the cost per dose and cost per FIG. Results Over five years (2011 to 2015, the cost of establishing an HPV vaccine program that delivers three doses of vaccine to girls at schools via phased national introduction (three regions in year 1, ten regions in year 2 and all 26 regions in years 3 to 5 in Tanzania is estimated to be US$9.2 million (excluding vaccine costs and US$31.5 million (with vaccine assuming a vaccine price of US$5 (GAVI 2011, formerly the Global Alliance for Vaccines and Immunizations. This is equivalent to a

Intranasal delivery of a protein subunit vaccine using a Tobacco Mosaic Virus platform protects against pneumonic plague.

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Arnaboldi, Paul M; Sambir, Mariya; D'Arco, Christina; Peters, Lauren A; Seegers, Jos F M L; Mayer, Lloyd; McCormick, Alison A; Dattwyler, Raymond J

2016-11-11

Yersinia pestis, one of history's deadliest pathogens, has killed millions over the course of human history. It has attributes that make it an ideal choice to produce mass casualties and is a prime candidate for use as a biological weapon. When aerosolized, Y. pestis causes pneumonic plague, a pneumonia that is 100% lethal if not promptly treated with effective antibiotics. Currently, there is no FDA approved plague vaccine. The current lead vaccine candidate, a parenterally administered protein subunit vaccine comprised of the Y. pestis virulence factors, F1 and LcrV, demonstrated variable levels of protection in primate pneumonic plague models. As the most likely mode of exposure in biological attack with Y. pestis is by aerosol, this raises a question of whether this parenteral vaccine will adequately protect humans against pneumonic plague. In the present study we evaluated two distinct mucosal delivery platforms for the intranasal (IN) administration of LcrV and F1 vaccine proteins, a live bacterial vector, Lactobacillus plantarum, and a Tobacco Mosaic Virus (TMV) based delivery platform. IN administration of L. plantarum expressing LcrV, or TMV-conjugated to LcrV and F1 (TMV-LcrV+TMV-F1) resulted in the similar induction of high titers of IgG antibodies and evidence of proinflammatory cytokine secretion. However, only the TMV-conjugate delivery platform protected against subsequent lethal challenge with Y. pestis. TMV-LcrV+TMV-F1 co-vaccinated mice had no discernable morbidity and no mortality, while mice vaccinated with L. plantarum expressing LcrV or rLcrV+rF1 without TMV succumbed to infection or were only partially protected. Thus, TMV is a suitable mucosal delivery platform for an F1-LcrV subunit vaccine that induces complete protection against pneumonic infection with a lethal dose of Y. pestis in mice. Copyright © 2016 Elsevier Ltd. All rights reserved.

Nanoparticle enabled transdermal drug delivery systems for enhanced dose control and tissue targeting

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Palmer, Brian C.; DeLouise, Lisa A.

2017-01-01

Transdermal drug delivery systems have been around for decades, and current technologies (e.g. patches, ointments, and creams) enhance the skin permeation of low molecular weight, lipophilic drugs that are efficacious at low doses. The objective of current transdermal drug delivery research is to discover ways to enhance skin penetration of larger, hydrophilic drugs and macromolecules for disease treatment and vaccination. Nanocarriers made of lipids, metals, or polymers have been successfully used to increase penetration of drugs or vaccines, control drug release, and target drugs to specific areas of skin in vivo. While more research is needed to identify the safety of nanocarriers, this technology has the potential to expand the use of transdermal routes of administration to a wide array of therapeutics. Here, we review the current state of nanoparticle skin delivery systems with special emphasis on targeting skin diseases. PMID:27983701

Nanoparticle-Enabled Transdermal Drug Delivery Systems for Enhanced Dose Control and Tissue Targeting.

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Palmer, Brian C; DeLouise, Lisa A

2016-12-15

Transdermal drug delivery systems have been around for decades, and current technologies (e.g., patches, ointments, and creams) enhance the skin permeation of low molecular weight, lipophilic drugs that are efficacious at low doses. The objective of current transdermal drug delivery research is to discover ways to enhance skin penetration of larger, hydrophilic drugs and macromolecules for disease treatment and vaccination. Nanocarriers made of lipids, metals, or polymers have been successfully used to increase penetration of drugs or vaccines, control drug release, and target drugs to specific areas of skin in vivo. While more research is needed to identify the safety of nanocarriers, this technology has the potential to expand the use of transdermal routes of administration to a wide array of therapeutics. Here, we review the current state of nanoparticle skin delivery systems with special emphasis on targeting skin diseases.

An oral microjet vaccination system elicits antibody production in rabbits.

Science.gov (United States)

Aran, Kiana; Chooljian, Marc; Paredes, Jacobo; Rafi, Mohammad; Lee, Kunwoo; Kim, Allison Y; An, Jeanny; Yau, Jennifer F; Chum, Helen; Conboy, Irina; Murthy, Niren; Liepmann, Dorian

2017-03-08

Noninvasive immunization technologies have the potential to revolutionize global health by providing easy-to-administer vaccines at low cost, enabling mass immunizations during pandemics. Existing technologies such as transdermal microneedles are costly, deliver drugs slowly, and cannot generate mucosal immunity, which is important for optimal immunity against pathogens. We present a needle-free microjet immunization device termed MucoJet, which is a three-dimensional microelectromechanical systems-based drug delivery technology. MucoJet is administered orally, placed adjacent to the buccal tissue within the oral cavity, and uses a self-contained gas-generating chemical reaction within its two-compartment plastic housing to produce a high-pressure liquid jet of vaccine. We show that the vaccine jet ejected from the MucoJet device is capable of penetrating the buccal mucosal layer in silico, in porcine buccal tissue ex vivo, and in rabbits in vivo. Rabbits treated with ovalbumin by MucoJet delivery have antibody titers of anti-ovalbumin immunoglobulins G and A in blood serum and buccal tissue, respectively, that are three orders of magnitude higher than rabbits receiving free ovalbumin delivered topically by a dropper in the buccal region. MucoJet has the potential to accelerate the development of noninvasive oral vaccines, given its ability to elicit antibody production that is detectable locally in the buccal tissue and systemically via the circulation. Copyright © 2017, American Association for the Advancement of Science.

Enhanced immunization via dissolving microneedle array-based delivery system incorporating subunit vaccine and saponin adjuvant.

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Zhao, Ji-Hui; Zhang, Qi-Bo; Liu, Bao; Piao, Xiang-Hua; Yan, Yu-Lu; Hu, Xiao-Ge; Zhou, Kuan; Zhang, Yong-Tai; Feng, Nian-Ping

2017-01-01

To enhance the immunogenicity of the model subunit vaccine, ovalbumin (OVA) was combined with platycodin (PD), a saponin adjuvant. To reduce the toxicity of PD, OVA, and adjuvant were loaded together into liposomes before being incorporated into a dissolving microneedle array. OVA- and PD-loaded liposomes (OVA-PD-Lipos) were prepared using the film dispersion method. Their uptake behavior, toxicity to mouse bone marrow dendritic cells (BMDCs), and hemolytic activity to rabbit red blood cells (RBCs) were evaluated. The OVA-PD-Lipos were incorporated into a dissolving microneedle array. The chemical stability of OVA and the physical stability of OVA-PD-Lipos in microneedle arrays were investigated. The immune response of Institute of Cancer Research mice and potential skin irritation reaction of rabbits to OVA-PD-Lipos-MNs were evaluated. The uptake of OVA by mouse BMDCs was greatly enhanced when OVA was prepared as OVA-PD-Lipos, and in this form, the toxicity of PD was dramatically reduced. OVA was chemically stable as OVA-PD-Lipos, when OVA-PD-Lipos was incorporated into a dissolving microneedle array. Institute of Cancer Research mice treated with OVA-PD-Lipos-MNs showed a significantly enhanced immune response. PD combined with OVA elicited a balanced Th1 and Th2 humoral immune response in mice, with minimal irritation in rabbit skin. The dissolving microneedle array-based system is a promising delivery vehicle for subunit vaccine and its adjuvant.

Nanoparticle-Enabled Transdermal Drug Delivery Systems for Enhanced Dose Control and Tissue Targeting

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Brian C. Palmer

2016-12-01

Full Text Available Transdermal drug delivery systems have been around for decades, and current technologies (e.g., patches, ointments, and creams enhance the skin permeation of low molecular weight, lipophilic drugs that are efficacious at low doses. The objective of current transdermal drug delivery research is to discover ways to enhance skin penetration of larger, hydrophilic drugs and macromolecules for disease treatment and vaccination. Nanocarriers made of lipids, metals, or polymers have been successfully used to increase penetration of drugs or vaccines, control drug release, and target drugs to specific areas of skin in vivo. While more research is needed to identify the safety of nanocarriers, this technology has the potential to expand the use of transdermal routes of administration to a wide array of therapeutics. Here, we review the current state of nanoparticle skin delivery systems with special emphasis on targeting skin diseases.

Re-designing the Mozambique vaccine supply chain to improve access to vaccines.

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Lee, Bruce Y; Haidari, Leila A; Prosser, Wendy; Connor, Diana L; Bechtel, Ruth; Dipuve, Amelia; Kassim, Hidayat; Khanlawia, Balbina; Brown, Shawn T

2016-09-22

Populations and routine childhood vaccine regimens have changed substantially since supply chains were designed in the 1980s, and introducing new vaccines during the "Decade of Vaccine" may exacerbate existing bottlenecks, further inhibiting the flow of all vaccines. Working with the Mozambique Ministry of Health, our team implemented a new process that integrated HERMES computational simulation modeling and on-the-ground implementers to evaluate and improve the Mozambique vaccine supply chain using a system-re-design that integrated new supply chain structures, information technology, equipment, personnel, and policies. The alternative system design raised vaccine availability (from 66% to 93% in Gaza; from 76% to 84% in Cabo Delgado) and reduced the logistics cost per dose administered (from $0.53 to $0.32 in Gaza; from $0.38 to $0.24 in Cabo Delgado) as compared to the multi-tiered system under the current EPI. The alternative system also produced higher availability at lower costs after new vaccine introductions. Since reviewing scenarios modeling deliveries every two months in the north of Gaza, the provincial directorate has decided to pilot this approach diverging from decades of policies dictating monthly deliveries. Re-design improved not only supply chain efficacy but also efficiency, important since resources to deliver vaccines are limited. The Mozambique experience and process can serve as a model for other countries during the Decade of Vaccines. For the Decade of Vaccines, getting vaccines at affordable prices to the market is not enough. Vaccines must reach the population to be successful. Copyright © 2016. Published by Elsevier Ltd.

School-based vaccination programmes: a systematic review of the evidence on organisation and delivery in high income countries

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Sarah Perman

2017-03-01

Full Text Available Abstract Background Many countries have recently expanded their childhood immunisation programmes. Schools are an increasingly attractive setting for delivery of these new immunisations because of their ability to reach large numbers of children in a short period of time. However, there are organisational challenges to delivery of large-scale vaccination programmes in schools. Understanding the facilitators and barriers is important for improving the delivery of future school-based vaccination programmes. Methods We undertook a systematic review of evidence on school-based vaccination programmes in order to understand the influence of organisational factors on the delivery of programmes. Our eligibility criteria were studies that (1 focused on childhood or adolescent vaccination programmes delivered in schools; (2 considered organisational factors that influenced the preparation or delivery of programmes; (3 were conducted in a developed or high-income country; and (4 had been peer reviewed. We searched for articles published in English between 2000 and 2015 using MEDLINE and HMIC electronic databases. Additional studies were identified by searching the Cochrane Library and bibliographies. We extracted data from the studies, assessed quality and the risk of bias, and categorised findings using a thematic framework of eight organisational factors. Results We found that most of the recent published literature is from the United States and is concerned with the delivery of pandemic or seasonal flu vaccination programmes at a regional (state or local level. We found that the literature is largely descriptive and not informed by the use of theory. Despite this, we identified common factors that influence the implementation of programmes. These factors included programme leadership and governance, organisational models and institutional relationships, workforce capacity and roles particularly concerning the school nurse, communication with parents and

Microneedle arrays coated with charge reversal pH-sensitive copolymers improve antigen presenting cells-homing DNA vaccine delivery and immune responses.

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Duong, Huu Thuy Trang; Kim, Nak Won; Thambi, Thavasyappan; Giang Phan, V H; Lee, Min Sang; Yin, Yue; Jeong, Ji Hoon; Lee, Doo Sung

2018-01-10

Successful delivery of a DNA vaccine to antigen-presenting cells and their subsequent stimulation of CD4 + and CD8 + T cell immunity remains an inefficient process. In general, the delivery of prophylactic vaccines is mainly mired by low transfection efficacy, poor immunogenicity, and safety issues from the materials employed. Currently, several strategies have been exploited to improve immunogenicity, but an effective strategy for safe and pain-free delivery of DNA vaccines is complicated. Herein, we report the rapid delivery of polyplex-based DNA vaccines using microneedle arrays coated with a polyelectrolyte multilayer assembly of charge reversal pH-responsive copolymer and heparin. The charge reversal pH-responsive copolymer, composed of oligo(sulfamethazine)-b-poly(ethylene glycol)-b-poly(amino urethane) (OSM-b-PEG-b-PAEU), was used as a triggering layer in the polyelectrolyte multilayer assembly on microneedles. Charge reversal characteristics of this copolymer, that is, the OSM-b-PEG-b-PAEU copolymer exhibit, positive charge at low pH (pH4.03) and becoming negative charge when exposed to physiological pH conditions (pH7.4), allowing the facile assembly and disassembly of polyelectrolyte multilayers. The electrostatic repulsion between heparin and OSM-b-PEG-b-PAEU charge reversal copolymer triggered the release of DNA vaccines. DNA vaccines laden on microneedles are effectively transfected into RAW 264.7 macrophage cells in vitro. Vaccination of BALB/c mice by DNA vaccine-loaded microneedle arrays coated with a polyelectrolyte multilayer generated antigen-specific robust immune responses. These findings provide potential strategy of charge reversal pH-responsive copolymers coated microneedles for DNA vaccine delivery. Copyright © 2017. Published by Elsevier B.V.

Percutaneous Vaccination as an Effective Method of Delivery of MVA and MVA-Vectored Vaccines.

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Clement A Meseda

Full Text Available The robustness of immune responses to an antigen could be dictated by the route of vaccine inoculation. Traditional smallpox vaccines, essentially vaccinia virus strains, that were used in the eradication of smallpox were administered by percutaneous inoculation (skin scarification. The modified vaccinia virus Ankara is licensed as a smallpox vaccine in Europe and Canada and currently undergoing clinical development in the United States. MVA is also being investigated as a vector for the delivery of heterologous genes for prophylactic or therapeutic immunization. Since MVA is replication-deficient, MVA and MVA-vectored vaccines are often inoculated through the intramuscular, intradermal or subcutaneous routes. Vaccine inoculation via the intramuscular, intradermal or subcutaneous routes requires the use of injection needles, and an estimated 10 to 20% of the population of the United States has needle phobia. Following an observation in our laboratory that a replication-deficient recombinant vaccinia virus derived from the New York City Board of Health strain elicited protective immune responses in a mouse model upon inoculation by tail scarification, we investigated whether MVA and MVA recombinants can elicit protective responses following percutaneous administration in mouse models. Our data suggest that MVA administered by percutaneous inoculation, elicited vaccinia-specific antibody responses, and protected mice from lethal vaccinia virus challenge, at levels comparable to or better than subcutaneous or intramuscular inoculation. High titers of specific neutralizing antibodies were elicited in mice inoculated with a recombinant MVA expressing the herpes simplex type 2 glycoprotein D after scarification. Similarly, a recombinant MVA expressing the hemagglutinin of attenuated influenza virus rgA/Viet Nam/1203/2004 (H5N1 elicited protective immune responses when administered at low doses by scarification. Taken together, our data suggest that

Percutaneous Vaccination as an Effective Method of Delivery of MVA and MVA-Vectored Vaccines.

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Meseda, Clement A; Atukorale, Vajini; Kuhn, Jordan; Schmeisser, Falko; Weir, Jerry P

2016-01-01

The robustness of immune responses to an antigen could be dictated by the route of vaccine inoculation. Traditional smallpox vaccines, essentially vaccinia virus strains, that were used in the eradication of smallpox were administered by percutaneous inoculation (skin scarification). The modified vaccinia virus Ankara is licensed as a smallpox vaccine in Europe and Canada and currently undergoing clinical development in the United States. MVA is also being investigated as a vector for the delivery of heterologous genes for prophylactic or therapeutic immunization. Since MVA is replication-deficient, MVA and MVA-vectored vaccines are often inoculated through the intramuscular, intradermal or subcutaneous routes. Vaccine inoculation via the intramuscular, intradermal or subcutaneous routes requires the use of injection needles, and an estimated 10 to 20% of the population of the United States has needle phobia. Following an observation in our laboratory that a replication-deficient recombinant vaccinia virus derived from the New York City Board of Health strain elicited protective immune responses in a mouse model upon inoculation by tail scarification, we investigated whether MVA and MVA recombinants can elicit protective responses following percutaneous administration in mouse models. Our data suggest that MVA administered by percutaneous inoculation, elicited vaccinia-specific antibody responses, and protected mice from lethal vaccinia virus challenge, at levels comparable to or better than subcutaneous or intramuscular inoculation. High titers of specific neutralizing antibodies were elicited in mice inoculated with a recombinant MVA expressing the herpes simplex type 2 glycoprotein D after scarification. Similarly, a recombinant MVA expressing the hemagglutinin of attenuated influenza virus rgA/Viet Nam/1203/2004 (H5N1) elicited protective immune responses when administered at low doses by scarification. Taken together, our data suggest that MVA and MVA

Gut-associated lymphoid tissues for the development of oral vaccines.

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Kunisawa, Jun; Kurashima, Yosuke; Kiyono, Hiroshi

2012-05-01

Oral vaccine has been considered to be a prospective vaccine against many pathogens especially invading across gastrointestinal tracts. One key element of oral vaccine is targeting efficient delivery of antigen to gut-associated lymphoid tissue (GALT), the inductive site in the intestine where antigen-specific immune responses are initiated. Various chemical and biological antigen delivery systems have been developed and some are in clinical trials. In this review, we describe the immunological features of GALT and the current status of antigen delivery system candidates for successful oral vaccine. Copyright © 2011 Elsevier B.V. All rights reserved.

Diphtheria toxoid loaded poly-(epsilon-caprolactone) nanoparticles as mucosal vaccine delivery systems.

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Singh, Jasvinder; Pandit, Sreenivas; Bramwell, Vincent W; Alpar, H Oya

2006-02-01

Poly-(epsilon-caprolactone) (PCL), a poly(lactide-co-glycolide) (PLGA)-PCL blend and co-polymer nanoparticles encapsulating diphtheria toxoid (DT) were investigated for their potential as a mucosal vaccine delivery system. The nanoparticles, prepared using a water-in-oil-in-water (w/o/w) double emulsion solvent evaporation method, demonstrated release profiles which were dependent on the properties of the polymers. An in vitro experiment using Caco-2 cells showed significantly higher uptake of PCL nanoparticles in comparison to polymeric PLGA, the PLGA-PCL blend and co-polymer nanoparticles. The highest uptake mediated by the most hydrophobic nanoparticles using Caco-2 cells was mirrored in the in vivo studies following nasal administration. PCL nanoparticles induced DT serum specific IgG antibody responses significantly higher than PLGA. A significant positive correlation between hydrophobicity of the nanoparticles and the immune response was observed following intramuscular administration. The positive correlation between hydrophobicity of the nanoparticles and serum DT specific IgG antibody response was also observed after intranasal administration of the nanoparticles. The cytokine assays showed that the serum IgG antibody response induced is different according to the route of administration, indicated by the differential levels of IL-6 and IFN-gamma. The nanoparticles eliciting the highest IgG antibody response did not necessarily elicit the highest levels of the cytokines IL-6 and IFN-gamma.

Stabilization challenges and formulation strategies associated with oral biologic drug delivery systems.

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Truong-Le, Vu; Lovalenti, Phillip M; Abdul-Fattah, Ahmad M

2015-10-01

Delivery of proteins to mucosal tissues of GI tract typically utilize formulations which protect against proteolysis and target the mucosal tissues. Using case studies from literature and the authors' own work, the in-process stability and solid state storage stability of biopharmaceuticals formulated in delivery systems designed for oral delivery to the GI tract will be reviewed. Among the range of delivery systems, biodegradable polymer systems for protection and controlled release of proteins have been the most studied; hence these systems will be covered in greater depth. These delivery systems include polymeric biodegradable microspheres or nanospheres that contain proteins or vaccines, which are designed to reduce the number of administrations/inoculations and the total protein dose required to achieve the desired biological effect. Specifically, this review will include a landscape survey of the systems that have been studied, the manufacturing processes involved, stability through the manufacturing process, key pharmaceutical formulation parameters that impact stability of the encased proteins, and storage stability of the encapsulated proteins in these delivery systems. Copyright © 2015 Elsevier B.V. All rights reserved.

Estimating the cost of cholera-vaccine delivery from the societal point of view: A case of introduction of cholera vaccine in Bangladesh.

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Sarker, Abdur Razzaque; Islam, Ziaul; Khan, Iqbal Ansary; Saha, Amit; Chowdhury, Fahima; Khan, Ashraful Islam; Cravioto, Alejandro; Clemens, John David; Qadri, Firdausi; Khan, Jahangir A M

2015-09-11

Cholera is a major global public health problem that causes both epidemic and endemic disease. The World Health Organization recommends oral cholera vaccines as a public health tool in addition to traditional prevention practices and treatments in both epidemic and endemic settings. In many developing countries like Bangladesh, the major issue concerns the affordability of this vaccine. In February 2011, a feasibility study entitled, "Introduction of Cholera Vaccine in Bangladesh (ICVB)", was conducted for a vaccination campaign using inactivated whole-cell cholera vaccine (Shanchol) in a high risk area of Mirpur, Dhaka. Empirical data obtained from this trial was used to determine the vaccination cost for a fully immunized person from the societal perspective. A total of 123,661 people were fully vaccinated receiving two doses of the vaccine, while 18,178 people received one dose of the same vaccine. The total cost for vaccine delivery was US$ 492,238 giving a total vaccination cost per fully-vaccinated individual of US$ 3.98. The purchase cost of the vaccine accounted for 58% of the overall cost of vaccination. Attempts to reduce the per-dose cost of the vaccine are likely to have a large impact on the cost of similar vaccination campaigns in the future. Copyright © 2015 Elsevier Ltd. All rights reserved.

Delivery Systems for Biopharmaceuticals. Part I: Nanoparticles and Microparticles.

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Silva, Ana C; Lopes, Carla M; Lobo, José M S; Amaral, Maria H

2015-01-01

Pharmaceutical biotechnology has been showing therapeutic success never achieved with conventional drug molecules. Therefore, biopharmaceutical products are currently well-established in clinic and the development of new ones is expected. These products comprise mainly therapeutic proteins, although nucleic acids and cells are also included. However, according to their sensitive molecular structures, the efficient delivery of biopharmaceuticals is challenging. Several delivery systems (e.g. microparticles and nanoparticles) composed of different materials (e.g. polymers and lipids) have been explored and demonstrated excellent outcomes, such as: high cellular transfection efficiency for nucleic acids, cell targeting, increased proteins and peptides bioavailability, improved immune response in vaccination, and viability maintenance of microencapsulated cells. Nonetheless, important issues need to be addressed before they reach clinics. For example, more in vivo studies in animals, accessing the toxicity potential and predicting in vivo failure of these delivery systems are required. This is the Part I of two review articles, which presents the state of the art of delivery systems for biopharmaceuticals. Part I deals with microparticles and polymeric and lipid nanoparticles.

Innovative vaccine delivery strategies in response to a cholera outbreak in the challenging context of Lake Chilwa. A rapid qualitative assessment.

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Heyerdahl, Leonard W; Ngwira, Bagrey; Demolis, Rachel; Nyirenda, Gabriel; Mwesawina, Maurice; Rafael, Florentina; Cavailler, Philippe; Bernard Le Gargasson, Jean; Mengel, Martin A; Gessner, Bradford D; Guillermet, Elise

2017-11-07

A reactive campaign using two doses of Shanchol Oral Cholera Vaccine (OCV) was implemented in 2016 in the Lake Chilwa Region (Malawi) targeting fish dependent communities. Three strategies for the second vaccine dose delivery (including delivery by a community leader and self-administration) were used to facilitate vaccine access. This assessment collected vaccine perceptions and opinions about the OCV campaign of 313 study participants, including: fishermen, fish traders, farmers, community leaders, and one health and one NGO officer. Socio-demographic surveys were conducted, In Depth Interviews and Focus Group Discussions were conducted before and during the campaign. Some fishermen perceived the traditional delivery strategy as reliable but less practical. Delivery by traditional leaders was acceptable for some participants while others worried about traditional leaders not being trained to deliver vaccines or beneficiaries taking doses on their own. A slight majority of beneficiaries considered the self-administration strategy practical while some beneficiaries worried about storing vials outside of the cold chain or losing vials. During the campaign, a majority of participants preferred receiving oral vaccines instead of injections given ease of intake and lack of pain. OCV was perceived as efficacious and safe. However, a lack of information on how sero-protection may be delayed and the degree of sero-protection led to loss of trust in vaccine potency among some participants who witnessed cholera cases among vaccinated individuals. OCV campaign implementation requires accompanying communication on protective levels, less than 100% vaccine efficacy, delays in onset of sero-protection, and out of cold chain storage. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Comparison of chitosan nanoparticles and chitosan hydrogels for vaccine delivery

DEFF Research Database (Denmark)

Gordon, Sarah; Saupe, Anne; McBurney, Warren

2008-01-01

In this work the potential of chitosan nanoparticles (CNP) and thermosensitive chitosan hydrogels as particulate and sustained release vaccine delivery systems was investigated. CNP and chitosan hydrogels were prepared, loaded with the model protein antigen ovalbumin (OVA) and characterised...... of the release of fluorescently-labelled OVA (FITC-OVA) from CNP and chitosan hydrogels in-vitro showed that approximately 50% of the total protein was released from CNP within a period of ten days; release of antigen from chitosan gel occurred in a more sustained manner, with ... released after 10 days. The slow release from gel formulations may be explained by the strong interactions of the protein with chitosan. While OVA-loaded CNP showed no significant immunogenicity, formulations of OVA in chitosan gel were able to stimulate both cell-mediated and humoral immunity in-vivo....

An Overview on the Field of Micro- and Nanotechnologies for Synthetic Peptide-Based Vaccines

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Aiala Salvador

2011-01-01

Full Text Available The development of synthetic peptide-based vaccines has many advantages in comparison with vaccines based on live attenuated organisms, inactivated or killed organism, or toxins. Peptide-based vaccines cannot revert to a virulent form, allow a better conservation, and are produced more easily and safely. However, they generate a weaker immune response than other vaccines, and the inclusion of adjuvants and/or the use of vaccine delivery systems is almost always needed. Among vaccine delivery systems, micro- and nanoparticulated ones are attractive, because their particulate nature can increase cross-presentation of the peptide. In addition, they can be passively or actively targeted to antigen presenting cells. Furthermore, particulate adjuvants are able to directly activate innate immune system in vivo. Here, we summarize micro- and nanoparticulated vaccine delivery systems used in the field of synthetic peptide-based vaccines as well as strategies to increase their immunogenicity.

Potential Cost-Effectiveness of an Influenza Vaccination Program Offering Microneedle Patch for Vaccine Delivery in Children.

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Carlos Wong

Full Text Available The influenza vaccine coverage rate of children is low in Hong Kong. Microneedle patches (MNPs is a technology under development for painless delivery of vaccines. This study aimed to examine the potential clinical outcomes and direct medical costs of an influenza program offering MNP vaccine to children who have declined intramuscular (IM vaccine in Hong Kong.A decision model was designed to compare potential outcomes between IM vaccine program and a program offering MNP vaccine to those declined IM vaccine (IM/MNP program in a hypothetical cohort of children over one-year time horizon. The model outcomes included direct medical cost, influenza infection rate, mortality rate, and quality-adjusted life-years (QALYs loss. Model inputs were retrieved from published literature. Sensitivity analyses were performed to examine the robustness of model results.In base-case analysis, IM/MNP program was more costly per child (USD19.13 versus USD13.69; USD1 = HKD7.8 with lower influenza infection rate (98.9 versus 124.8 per 1,000 children, hospitalization rate (0.83 versus 1.05 per 1,000 children and influenza-related mortality rate (0.00042 versus 0.00052 per 1,000 children when compared to IM program. The incremental cost per QALY saved (ICER of IM/MNP program versus IM program was 27,200 USD/QALY. Using gross domestic product (GDP per capita of Hong Kong (USD40,594 as threshold of willingness-to-pay (WTP per QALY, one-way sensitivity analysis found ICER of IM/MNP to exceed WTP when duration of illness in outpatient setting was 1.39-time of IM vaccine cost. In 10,000 Monte Carlo simulations, IM/MNP program was the preferred option in 57.28% and 91.68% of the time, using 1x and 3x GDP per capita as WTP threshold, respectively.Acceptance of IM/MNP program as the preferred program was subject to the WTP threshold, duration of illness in outpatient settings, and cost of MNP vaccine.

Development of chitosan-pullulan composite nanoparticles for nasal delivery of vaccines: in vivo studies.

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Cevher, Erdal; Salomon, Stefan K; Somavarapu, Satyanarayana; Brocchini, Steve; Alpar, H Oya

2015-01-01

Here, we aimed at developing chitosan/pullulan composite nanoparticles and testing their potential as novel systems for the nasal delivery of diphtheria toxoid (DT). All the chitosan derivatives [N-trimethyl (TMC), chloride and glutamate] and carboxymethyl pullulan (CMP) were synthesised and antigen-loaded composites were prepared by polyion complexation of chitosan and pullulan derivatives (particle size: 239-405 nm; surface charge: +18 and +27 mV). Their immunological effects after intranasal administration to mice were compared to intramuscular route. Composite nanoparticles induced higher levels of IgG responses than particles formed with chitosan derivative and antigen. Nasally administered TMC-pullulan composites showed higher DT serum IgG titre when compared with the other composites. Co-encapsulation of CpG ODN within TMC-CMP-DT nanoparticles resulted in a balanced Th1/Th2 response. TMC/pullulan composite nanoparticles also induced highest cytokine levels compared to those of chitosan salts. These findings demonstrated that TMC-CMP-DT composite nanoparticles are promising delivery system for nasal vaccination.

Self-amplifying mRNA vaccines.

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Brito, Luis A; Kommareddy, Sushma; Maione, Domenico; Uematsu, Yasushi; Giovani, Cinzia; Berlanda Scorza, Francesco; Otten, Gillis R; Yu, Dong; Mandl, Christian W; Mason, Peter W; Dormitzer, Philip R; Ulmer, Jeffrey B; Geall, Andrew J

2015-01-01

This chapter provides a brief introduction to nucleic acid-based vaccines and recent research in developing self-amplifying mRNA vaccines. These vaccines promise the flexibility of plasmid DNA vaccines with enhanced immunogenicity and safety. The key to realizing the full potential of these vaccines is efficient delivery of nucleic acid to the cytoplasm of a cell, where it can amplify and express the encoded antigenic protein. The hydrophilicity and strong net negative charge of RNA impedes cellular uptake. To overcome this limitation, electrostatic complexation with cationic lipids or polymers and physical delivery using electroporation or ballistic particles to improve cellular uptake has been evaluated. This chapter highlights the rapid progress made in using nonviral delivery systems for RNA-based vaccines. Initial preclinical testing of self-amplifying mRNA vaccines has shown nonviral delivery to be capable of producing potent and robust innate and adaptive immune responses in small animals and nonhuman primates. Historically, the prospect of developing mRNA vaccines was uncertain due to concerns of mRNA instability and the feasibility of large-scale manufacturing. Today, these issues are no longer perceived as barriers in the widespread implementation of the technology. Currently, nonamplifying mRNA vaccines are under investigation in human clinical trials and can be produced at a sufficient quantity and quality to meet regulatory requirements. If the encouraging preclinical data with self-amplifying mRNA vaccines are matched by equivalently positive immunogenicity, potency, and tolerability in human trials, this platform could establish nucleic acid vaccines as a versatile new tool for human immunization. Copyright © 2015 Elsevier Inc. All rights reserved.

Evaluation of Mucosal and Systemic Immune Responses Elicited by GPI-0100-Adjuvanted Influenza Vaccine Delivered by Different Immunization Strategies

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Liu, Heng; Patil, Harshad P.; de Vries-Idema, Jacqueline; Wilschut, Jan; Huckriede, Anke

2013-01-01

Vaccines for protection against respiratory infections should optimally induce a mucosal immune response in the respiratory tract in addition to a systemic immune response. However, current parenteral immunization modalities generally fail to induce mucosal immunity, while mucosal vaccine delivery

Langerin negative dendritic cells promote potent CD8+ T-cell priming by skin delivery of live adenovirus vaccine microneedle arrays.

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Bachy, Veronique; Hervouet, Catherine; Becker, Pablo D; Chorro, Laurent; Carlin, Leo M; Herath, Shanthi; Papagatsias, Timos; Barbaroux, Jean-Baptiste; Oh, Sea-Jin; Benlahrech, Adel; Athanasopoulos, Takis; Dickson, George; Patterson, Steven; Kwon, Sung-Yun; Geissmann, Frederic; Klavinskis, Linda S

2013-02-19

Stabilization of virus protein structure and nucleic acid integrity is challenging yet essential to preserve the transcriptional competence of live recombinant viral vaccine vectors in the absence of a cold chain. When coupled with needle-free skin delivery, such a platform would address an unmet need in global vaccine coverage against HIV and other global pathogens. Herein, we show that a simple dissolvable microneedle array (MA) delivery system preserves the immunogenicity of vaccines encoded by live recombinant human adenovirus type 5 (rAdHu5). Specifically, dried rAdHu5 MA immunization induced CD8(+) T-cell expansion and multifunctional cytokine responses equipotent with conventional injectable routes of immunization. Intravital imaging demonstrated MA cargo distributed both in the epidermis and dermis, with acquisition by CD11c(+) dendritic cells (DCs) in the dermis. The MA immunizing properties were attributable to CD11c(+) MHCII(hi) CD8α(neg) epithelial cell adhesion molecule (EpCAM(neg)) CD11b(+) langerin (Lang; CD207)(neg) DCs, but neither Langerhans cells nor Lang(+) DCs were required for CD8(+) T-cell priming. This study demonstrates an important technical advance for viral vaccine vectors progressing to the clinic and provides insights into the mechanism of CD8(+) T-cell priming by live rAdHu5 MAs.

Administration of HPV DNA vaccine via electroporation elicits the strongest CD8+ T cell immune responses compared to intramuscular injection and intradermal gene gun delivery

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Best, Simon R.; Peng, Shiwen; Juang, Chi-Mou; Hung, Chien-Fu; Hannaman, Drew; Saunders, John R.; Wu, T.-C.; Pai, Sara I.

2009-01-01

DNA vaccines are an attractive approach to eliciting antigen-specific immunity. Intracellular targeting of tumor antigens through its linkage to immunostimulatory molecules such as calreticulin (CRT) can improve antigen processing and presentation through the MHC Class I pathway and increase cytotoxic CD8+ T cell production. However, even with these enhancements, the efficacy of such immunotherapeutic strategies is dependent on the identification of an effective route and method of DNA administration. Electroporation and gene gun-mediated particle delivery are leading methods of DNA vaccine delivery that can generate protective and therapeutic levels of immune responses in experimental models. In this study, we perform a head-to-head comparison of three methods of vaccination – conventional intramuscular injection, electroporation mediated intramuscular delivery, and epidermal gene gun-mediated particle delivery - in the ability to generate antigen specific cytotoxic CD8+ T cell responses as well as anti-tumor immune responses against an HPV-16 E7 expressing tumor cell line using the pNGVL4a-CRT/E7(detox) DNA vaccine. Vaccination via electroporation generated the highest number of E7-specific cytotoxic CD8+ T cells, which correlated to improved outcomes in the treatment of growing tumors. In addition, we demonstrate that electroporation results in significantly higher levels of circulating protein compared to gene gun or intramuscular vaccination, which likely enhances calreticulin’s role as a local tumor anti-angiogenesis agent. We conclude that electroporation is a promising method for delivery of HPV DNA vaccines and should be considered for DNA vaccine delivery in human clinical trials. PMID:19622402

Oral Vaccination with Salmonella enterica as a Cruzipain-DNA Delivery System Confers Protective Immunity against Trypanosoma cruzi▿

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Cazorla, Silvia I.; Becker, Pablo D.; Frank, Fernanda M.; Ebensen, Thomas; Sartori, María J.; Corral, Ricardo S.; Malchiodi, Emilio L.; Guzmán, Carlos A.

2008-01-01

To stimulate both local and systemic immune responses against Trypanosoma cruzi, Salmonella enterica serovar Typhimurium aroA was exploited as a DNA delivery system for cruzipain (SCz). In a murine model we compared SCz alone (GI) or coadministered with Salmonella carrying a plasmid encoding granulocyte-macrophage colony-stimulating factor (GII), as well as protocols in which SCz priming was followed by boosting with recombinant cruzipain (rCz) admixed with either CpG-ODN (GIII) or MALP-2, a synthetic derivative of a macrophage-activating lipopeptide of 2 kDa from Mycoplasma fermentans (GIV). The results showed that protocols that included four oral doses of SCz (GI) elicited mainly a mucosal response characterized by immunoglobulin A (IgA) secretion and proliferation of gut-associated lymphoid tissue cells, with weak systemic responses. In contrast, the protocol that included a boost with rCz plus CpG (GIII) triggered stronger systemic responses in terms of Cz-specific serum IgG titers, splenocyte proliferation, gamma interferon (IFN-γ) secretion, and delayed-type hypersensitivity response. Trypomastigote challenge of vaccinated mice resulted in significantly lower levels of parasitemia compared to controls. Protection was abolished by depletion of either CD4+ or CD8+ T cells. Parasite control was also evident from the reduction of tissue damage, as revealed by histopathologic studies and serum levels of enzymes that are markers of muscle injury in chronic Chagas' disease (i.e., creatine kinase, aspartate aminotransferase, and lactate dehydrogenase). Enhanced release of IFN-γ and interleukin-2 was observed in GI and GII upon restimulation of splenocytes in the nonparasitic phase of infection. Our results indicate that Salmonella-mediated delivery of Cz-DNA by itself promotes the elicitation of an immune response that controls T. cruzi infection, thereby reducing parasite loads and subsequent damage to muscle tissues. PMID:17967857

Enhancing oral vaccine potency by targeting intestinal M cells.

Directory of Open Access Journals (Sweden)

Ali Azizi

2010-11-01

Full Text Available The immune system in the gastrointestinal tract plays a crucial role in the control of infection, as it constitutes the first line of defense against mucosal pathogens. The attractive features of oral immunization have led to the exploration of a variety of oral delivery systems. However, none of these oral delivery systems have been applied to existing commercial vaccines. To overcome this, a new generation of oral vaccine delivery systems that target antigens to gut-associated lymphoid tissue is required. One promising approach is to exploit the potential of microfold (M cells by mimicking the entry of pathogens into these cells. Targeting specific receptors on the apical surface of M cells might enhance the entry of antigens, initiating the immune response and consequently leading to protection against mucosal pathogens. In this article, we briefly review the challenges associated with current oral vaccine delivery systems and discuss strategies that might potentially target mouse and human intestinal M cells.

Ebola Vaccination Using a DNA Vaccine Coated on PLGA-PLL/γPGA Nanoparticles Administered Using a Microneedle Patch.

Science.gov (United States)

Yang, Hung-Wei; Ye, Ling; Guo, Xin Dong; Yang, Chinglai; Compans, Richard W; Prausnitz, Mark R

2017-01-01

Ebola DNA vaccine is incorporated into PLGA-PLL/γPGA nanoparticles and administered to skin using a microneedle (MN) patch. The nanoparticle delivery system increases vaccine thermostability and immunogenicity compared to free vaccine. Vaccination by MN patch produces stronger immune responses than intramuscular administration. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Microfabrication for Drug Delivery

Science.gov (United States)

Koch, Brendan; Rubino, Ilaria; Quan, Fu-Shi; Yoo, Bongyoung; Choi, Hyo-Jick

2016-01-01

This review is devoted to discussing the application of microfabrication technologies to target challenges encountered in life processes by the development of drug delivery systems. Recently, microfabrication has been largely applied to solve health and pharmaceutical science issues. In particular, fabrication methods along with compatible materials have been successfully designed to produce multifunctional, highly effective drug delivery systems. Microfabrication offers unique tools that can tackle problems in this field, such as ease of mass production with high quality control and low cost, complexity of architecture design and a broad range of materials. Presented is an overview of silicon- and polymer-based fabrication methods that are key in the production of microfabricated drug delivery systems. Moreover, the efforts focused on studying the biocompatibility of materials used in microfabrication are analyzed. Finally, this review discusses representative ways microfabrication has been employed to develop systems delivering drugs through the transdermal and oral route, and to improve drug eluting implants. Additionally, microfabricated vaccine delivery systems are presented due to the great impact they can have in obtaining a cold chain-free vaccine, with long-term stability. Microfabrication will continue to offer new, alternative solutions for the development of smart, advanced drug delivery systems. PMID:28773770

Potent immunity to low doses of influenza vaccine by probabilistic guided micro-targeted skin delivery in a mouse model.

Directory of Open Access Journals (Sweden)

Germain J P Fernando

Full Text Available BACKGROUND: Over 14 million people die each year from infectious diseases despite extensive vaccine use [1]. The needle and syringe--first invented in 1853--is still the primary delivery device, injecting liquid vaccine into muscle. Vaccines could be far more effective if they were precisely delivered into the narrow layer just beneath the skin surface that contains a much higher density of potent antigen-presenting cells (APCs essential to generate a protective immune response. We hypothesized that successful vaccination could be achieved this way with far lower antigen doses than required by the needle and syringe. METHODOLOGY/PRINCIPAL FINDINGS: To meet this objective, using a probability-based theoretical analysis for targeting skin APCs, we designed the Nanopatch, which contains an array of densely packed projections (21025/cm(2 invisible to the human eye (110 microm in length, tapering to tips with a sharpness of <1000 nm, that are dry-coated with vaccine and applied to the skin for two minutes. Here we show that the Nanopatches deliver a seasonal influenza vaccine (Fluvax 2008 to directly contact thousands of APCs, in excellent agreement with theoretical prediction. By physically targeting vaccine directly to these cells we induced protective levels of functional antibody responses in mice and also protection against an influenza virus challenge that are comparable to the vaccine delivered intramuscularly with the needle and syringe--but with less than 1/100(th of the delivered antigen. CONCLUSIONS/SIGNIFICANCE: Our results represent a marked improvement--an order of magnitude greater than reported by others--for injected doses administered by other delivery methods, without reliance on an added adjuvant, and with only a single vaccination. This study provides a proven mathematical/engineering delivery device template for extension into human studies--and we speculate that successful translation of these findings into humans could

Plant-made oral vaccines against human infectious diseases-Are we there yet?

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Chan, Hui-Ting; Daniell, Henry

2015-10-01

Although the plant-made vaccine field started three decades ago with the promise of developing low-cost vaccines to prevent infectious disease outbreaks and epidemics around the globe, this goal has not yet been achieved. Plants offer several major advantages in vaccine generation, including low-cost production by eliminating expensive fermentation and purification systems, sterile delivery and cold storage/transportation. Most importantly, oral vaccination using plant-made antigens confers both mucosal (IgA) and systemic (IgG) immunity. Studies in the past 5 years have made significant progress in expressing vaccine antigens in edible leaves (especially lettuce), processing leaves or seeds through lyophilization and achieving antigen stability and efficacy after prolonged storage at ambient temperatures. Bioencapsulation of antigens in plant cells protects them from the digestive system; the fusion of antigens to transmucosal carriers enhances efficiency of their delivery to the immune system and facilitates successful development of plant vaccines as oral boosters. However, the lack of oral priming approaches diminishes these advantages because purified antigens, cold storage/transportation and limited shelf life are still major challenges for priming with adjuvants and for antigen delivery by injection. Yet another challenge is the risk of inducing tolerance without priming the host immune system. Therefore, mechanistic aspects of these two opposing processes (antibody production or suppression) are discussed in this review. In addition, we summarize recent progress made in oral delivery of vaccine antigens expressed in plant cells via the chloroplast or nuclear genomes and potential challenges in achieving immunity against infectious diseases using cold-chain-free vaccine delivery approaches. © 2015 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

Tattoo Delivery of a Semliki Forest Virus-Based Vaccine Encoding Human Papillomavirus E6 and E7

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Stephanie van de Wall

2015-03-01

Full Text Available The skin is an attractive organ for immunization because of the presence of antigen-presenting cells. Intradermal delivery via tattooing has demonstrated superior vaccine immunogenicity of DNA vaccines in comparison to conventional delivery methods. In this study, we explored the efficacy of tattoo injection of a tumor vaccine based on recombinant Semliki Forest virus replicon particles (rSFV targeting human papillomavirus (HPV. Tattoo injection of rSFV particles resulted in antigen expression in both the skin and draining lymph nodes. In comparison with intramuscular injection, the overall antigen expression determined at the site of administration and draining lymph nodes was 10-fold lower upon tattoo injection. Delivery of SFV particles encoding the E6 and E7 antigens of human papillomavirus type 16 (SFVeE6,7 via tattooing resulted in HPV-specific cytotoxic T cells and in vivo therapeutic antitumor response. Strikingly, despite the observed lower overall transgene expression, SFVeE6,7 delivered via tattoo injection resulted in higher or equal levels of immune responses as compared to intramuscular injection. The intrinsic immunogenic potential of tattooing provides a benefit for immunotherapy based on an alphavirus.

Tattoo Delivery of a Semliki Forest Virus-Based Vaccine Encoding Human Papillomavirus E6 and E7

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van de Wall, Stephanie; Walczak, Mateusz; van Rooij, Nienke; Hoogeboom, Baukje-Nynke; Meijerhof, Tjarko; Nijman, Hans W.; Daemen, Toos

2015-01-01

The skin is an attractive organ for immunization because of the presence of antigen-presenting cells. Intradermal delivery via tattooing has demonstrated superior vaccine immunogenicity of DNA vaccines in comparison to conventional delivery methods. In this study, we explored the efficacy of tattoo injection of a tumor vaccine based on recombinant Semliki Forest virus replicon particles (rSFV) targeting human papillomavirus (HPV). Tattoo injection of rSFV particles resulted in antigen expression in both the skin and draining lymph nodes. In comparison with intramuscular injection, the overall antigen expression determined at the site of administration and draining lymph nodes was 10-fold lower upon tattoo injection. Delivery of SFV particles encoding the E6 and E7 antigens of human papillomavirus type 16 (SFVeE6,7) via tattooing resulted in HPV-specific cytotoxic T cells and in vivo therapeutic antitumor response. Strikingly, despite the observed lower overall transgene expression, SFVeE6,7 delivered via tattoo injection resulted in higher or equal levels of immune responses as compared to intramuscular injection. The intrinsic immunogenic potential of tattooing provides a benefit for immunotherapy based on an alphavirus. PMID:26343186

An update on the use of laser technology in skin vaccination

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Chen, Xinyuan; Wang, Ji; Shah, Dilip; Wu, Mei X

2014-01-01

Vaccination via skin often induces stronger immune responses than via muscle. This, in line with potential needle-free, painless delivery, makes skin a very attractive site for immunization. Yet, despite decades of effort, effective skin delivery is still in its infant stage and safe and potent adjuvants for skin vaccination remain largely undefined. We have shown that laser technologies including both fractional and non-fractional lasers can greatly augment vaccine-induced immune response without incurring any significant local and systemic side effects. Laser illumination at specific settings can accelerate the motility of antigen-presenting cells or trigger release of ‘danger’ signals stimulating the immune system. Moreover, several other groups including the authors explore laser technologies for needle-free transcutaneous vaccine delivery. As these laser-mediated resurfacing technologies are convenient, safe and cost-effective, their new applications in vaccination warrant clinical studies in the very near future. PMID:24127871

Effective nonvaccine interventions to be considered alongside human papilloma virus vaccine delivery.

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Hindin, Michelle J; Bloem, Paul; Ferguson, Jane

2015-01-01

World Health Organization recommends that girls, ages 9-13 years, get the human papilloma virus (HPV) vaccine. Global Alliance for Vaccines Initiative, which provides low-cost vaccine to eligible countries, requires that an additional intervention to be offered alongside the vaccine. We systematically searched and assessed the published literature in lower- and middle-income countries to identify effective interventions. We conducted systematic searches of four databases: PubMed, EMBASE, Global Index Medicus Regional Databases, and Cochrane Reviews for effective adolescent health interventions that could be delivered with the HPV vaccine in the following areas: (1) iron and folic acid supplementation (iron alone or with folic acid); (2) voucher delivery and cash transfer programs; (3) hand washing and soap provision; (4) vision screening; (5) promotion of physical activity/exercise; (6) menstrual hygiene education; (7) sexual and reproductive health education; (8) human immunodeficiency virus prevention activities; and (9) condom promotion, condom use skill building, and demonstration. We found limited evidence of consistent positive impact. Iron supplementation reduced iron-deficiency anemia and raised serum ferritin levels. Promotion of physical activity lowered blood pressure and reduced weight gain. Sexual and reproductive health and human immunodeficiency virus interventions improved adolescent communication with adults but did not influence behavioral outcomes. Countries should consider locally relevant and proven interventions to be offered alongside the HPV vaccine. Copyright © 2015 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Live RB51 vaccine lyophilized hydrogel formulations with increased shelf life for practical ballistic delivery

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Ballistic delivery capability is essential to delivering vaccines and other therapeutics effectively to both livestock and wildlife in many global scenarios. Here, lyophilized poly(ethylene glycol) (PEG)-glycolide dimethacrylate crosslinked but degradable hydrogels were assessed as payload vehicles ...

Effective vaccine safety systems in all countries: a challenge for more equitable access to immunization.

Science.gov (United States)

Amarasinghe, Ananda; Black, Steve; Bonhoeffer, Jan; Carvalho, Sandra M Deotti; Dodoo, Alexander; Eskola, Juhani; Larson, Heidi; Shin, Sunheang; Olsson, Sten; Balakrishnan, Madhava Ram; Bellah, Ahmed; Lambach, Philipp; Maure, Christine; Wood, David; Zuber, Patrick; Akanmori, Bartholomew; Bravo, Pamela; Pombo, María; Langar, Houda; Pfeifer, Dina; Guichard, Stéphane; Diorditsa, Sergey; Hossain, Md Shafiqul; Sato, Yoshikuni

2013-04-18

Serious vaccine-associated adverse events are rare. To further minimize their occurrence and to provide adequate care to those affected, careful monitoring of immunization programs and case management is required. Unfounded vaccine safety concerns have the potential of seriously derailing effective immunization activities. To address these issues, vaccine pharmacovigilance systems have been developed in many industrialized countries. As new vaccine products become available to prevent new diseases in various parts of the world, the demand for effective pharmacovigilance systems in low- and middle-income countries (LMIC) is increasing. To help establish such systems in all countries, WHO developed the Global Vaccine Safety Blueprint in 2011. This strategic plan is based on an in-depth analysis of the vaccine safety landscape that involved many stakeholders. This analysis reviewed existing systems and international vaccine safety activities and assessed the financial resources required to operate them. The Blueprint sets three main strategic goals to optimize the safety of vaccines through effective use of pharmacovigilance principles and methods: to ensure minimal vaccine safety capacity in all countries; to provide enhanced capacity for specific circumstances; and to establish a global support network to assist national authorities with capacity building and crisis management. In early 2012, the Global Vaccine Safety Initiative (GVSI) was launched to bring together and explore synergies among on-going vaccine safety activities. The Global Vaccine Action Plan has identified the Blueprint as its vaccine safety strategy. There is an enormous opportunity to raise awareness for vaccine safety in LMIC and to garner support from a large number of stakeholders for the GVSI between now and 2020. Synergies and resource mobilization opportunities presented by the Decade of Vaccines can enhance monitoring and response to vaccine safety issues, thereby leading to more equitable

Fc-based delivery system enhances immunogenicity of a tuberculosis subunit vaccine candidate consisting of the ESAT-6:CFP-10 complex.

Science.gov (United States)

Farsiani, Hadi; Mosavat, Arman; Soleimanpour, Saman; Sadeghian, Hamid; Akbari Eydgahi, Mohammad Reza; Ghazvini, Kiarash; Sankian, Mojtaba; Aryan, Ehsan; Jamehdar, Saeid Amel; Rezaee, Seyed Abdolrahim

2016-06-21

Tuberculosis (TB) remains a major global health threat despite chemotherapy and Bacilli Calmette-Guérin (BCG) vaccination. Therefore, a safer and more effective vaccine against TB is urgently needed. This study evaluated the immunogenicity of a recombinant fusion protein consisting of early secreted antigenic target protein 6 kDa (ESAT-6), culture filtrate protein 10 kDa (CFP-10) and the Fc-domain of mouse IgG2a as a novel subunit vaccine. The recombinant expression vectors (pPICZαA-ESAT-6:CFP-10:Fcγ2a and pPICZαA-ESAT-6:CFP-10:His) were transferred into Pichia pastoris. After SDS-PAGE and immunoblotting, the immunogenicity of the recombinant proteins was evaluated in mice. When both recombinant proteins (ESAT-6:CFP-10:Fcγ2a and ESAT-6:CFP-10:His) were used for vaccination, Th1-type cellular responses were induced producing high levels of IFN-γ and IL-12. However, the Fc-tagged recombinant protein induced more effective Th1-type cellular responses with a small increase in IL-4 as compared to the BCG and ESAT-6:CFP-10:His groups. Moreover, mice primed with BCG and then supplemented with ESAT-6:CFP-10:Fcγ2a produced the highest levels of IFN-γ and IL-12 in immunized groups. The findings indicate that when Fcγ2a is fused to the ESAT-6:CFP-10 complex, as a delivery vehicle, there could be an increase in the immunogenicity of this type of subunit vaccine. Therefore, additional investigations are necessary for the development of appropriate Fc-based tuberculosis vaccines.

Novel approaches to vaginal delivery and safety of microbicides: biopharmaceuticals, nanoparticles, and vaccines.

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Whaley, Kevin J; Hanes, Justin; Shattock, Robin; Cone, Richard A; Friend, David R

2010-12-01

The HIV-1 epidemic remains unchecked despite existing technology; vaccines and microbicides in development may help reverse the epidemic. Reverse transcriptase inhibitors (RTIs) formulated in gels tenofovir (TFV) and IVRs (dapivirine) are under clinical development. While TFV or similar products may prove successful for HIV-1, alternatives to RTIs may provide additional benefits, e.g., broader STI prevention. Biopharmaceutical agents under development as microbicides include cyanovirin, RANTES analogues, commensals, and Mabs. Cost of manufacturing biopharmaceuticals has been reduced and they can be formulated into tablets, films, and IVRs for vaginal delivery. Nanotechnology offers a novel approach to formulate microbicides potentially leading to uniform epithelial delivery. Delivery through vaginal mucus may be possible by controlling nanoparticle size and surface characteristics. Combining prevention modalities may be the most effective means of preventing STI transmission, importantly, codelivery of microbicides and vaccines has demonstrated. Finally, the safety of microbicide preparations and excipients commonly used can be assessed using a mouse/HSV-2 susceptibility model. Screening of new microbicide candidates and formulation excipients may avoid past issues of enhancing HIV-1 transmission. This article forms part of a special supplement covering several presentations on novel microbicide formulations from the symposium on "Recent Trends in Microbicide Formulations" held on 25 and 26 January 2010, Arlington, VA. Copyright © 2010 Elsevier B.V. All rights reserved.

Probability to produce animal vaccines in insect baculovirus ...

African Journals Online (AJOL)

Administrator

2011-09-07

Sep 7, 2011 ... The insect baculovirus expression system is a valuable tool for the production of vaccine. .... vaccine expression/delivery vehicle (Yu-Chen et al., ... baculoviruses are applied in cell-based assays for drug ... Intramuscular.

Vaccine Rejecting Parents' Engagement With Expert Systems That Inform Vaccination Programs.

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Attwell, Katie; Leask, Julie; Meyer, Samantha B; Rokkas, Philippa; Ward, Paul

2017-03-01

In attempting to provide protection to individuals and communities, childhood immunization has benefits that far outweigh disease risks. However, some parents decide not to immunize their children with some or all vaccines for reasons including lack of trust in governments, health professionals, and vaccine manufacturers. This article employs a theoretical analysis of trust and distrust to explore how twenty-seven parents with a history of vaccine rejection in two Australian cities view the expert systems central to vaccination policy and practice. Our data show how perceptions of the profit motive generate distrust in the expert systems pertaining to vaccination. Our participants perceived that pharmaceutical companies had a pernicious influence over the systems driving vaccination: research, health professionals, and government. Accordingly, they saw vaccine recommendations in conflict with the interests of their child and "the system" underscored by malign intent, even if individual representatives of this system were not equally tainted. This perspective was common to parents who declined all vaccines and those who accepted some. We regard the differences between these parents-and indeed the differences between vaccine decliners and those whose Western medical epistemology informs reflexive trust-as arising from the internalization of countering views, which facilitates nuance.

Antigen-displaying lipid-enveloped PLGA nanoparticles as delivery agents for a Plasmodium vivax malaria vaccine.

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Moon, James J; Suh, Heikyung; Polhemus, Mark E; Ockenhouse, Christian F; Yadava, Anjali; Irvine, Darrell J

2012-01-01

The parasite Plasmodium vivax is the most frequent cause of malaria outside of sub-Saharan Africa, but efforts to develop viable vaccines against P. vivax so far have been inadequate. We recently developed pathogen-mimicking polymeric vaccine nanoparticles composed of the FDA-approved biodegradable polymer poly(lactide-co-glycolide) acid (PLGA) "enveloped" by a lipid membrane. In this study, we sought to determine whether this vaccine delivery platform could be applied to enhance the immune response against P. vivax sporozoites. A candidate malaria antigen, VMP001, was conjugated to the lipid membrane of the particles, and an immunostimulatory molecule, monophosphoryl lipid A (MPLA), was incorporated into the lipid membranes, creating pathogen-mimicking nanoparticle vaccines (VMP001-NPs). Vaccination with VMP001-NPs promoted germinal center formation and elicited durable antigen-specific antibodies with significantly higher titers and more balanced Th1/Th2 responses in vivo, compared with vaccines composed of soluble protein mixed with MPLA. Antibodies raised by NP vaccinations also exhibited enhanced avidity and affinity toward the domains within the circumsporozoite protein implicated in protection and were able to agglutinate live P. vivax sporozoites. These results demonstrate that these VMP001-NPs are promising vaccines candidates that may elicit protective immunity against P. vivax sporozoites.

Antigen-displaying lipid-enveloped PLGA nanoparticles as delivery agents for a Plasmodium vivax malaria vaccine.

Directory of Open Access Journals (Sweden)

James J Moon

Full Text Available The parasite Plasmodium vivax is the most frequent cause of malaria outside of sub-Saharan Africa, but efforts to develop viable vaccines against P. vivax so far have been inadequate. We recently developed pathogen-mimicking polymeric vaccine nanoparticles composed of the FDA-approved biodegradable polymer poly(lactide-co-glycolide acid (PLGA "enveloped" by a lipid membrane. In this study, we sought to determine whether this vaccine delivery platform could be applied to enhance the immune response against P. vivax sporozoites. A candidate malaria antigen, VMP001, was conjugated to the lipid membrane of the particles, and an immunostimulatory molecule, monophosphoryl lipid A (MPLA, was incorporated into the lipid membranes, creating pathogen-mimicking nanoparticle vaccines (VMP001-NPs. Vaccination with VMP001-NPs promoted germinal center formation and elicited durable antigen-specific antibodies with significantly higher titers and more balanced Th1/Th2 responses in vivo, compared with vaccines composed of soluble protein mixed with MPLA. Antibodies raised by NP vaccinations also exhibited enhanced avidity and affinity toward the domains within the circumsporozoite protein implicated in protection and were able to agglutinate live P. vivax sporozoites. These results demonstrate that these VMP001-NPs are promising vaccines candidates that may elicit protective immunity against P. vivax sporozoites.

Engineering intranasal mRNA vaccines to enhance lymph node trafficking and immune responses.

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Li, Man; Li, You; Peng, Ke; Wang, Ying; Gong, Tao; Zhang, Zhirong; He, Qin; Sun, Xun

2017-12-01

Intranasal mRNA vaccination provides immediate immune protection against pandemic diseases. Recent studies have shown that diverse forms of polyethyleneimine (PEI) have potent mucosal adjuvant activity, which could significantly facilitate the delivery of intranasal mRNA vaccines. Nevertheless, optimizing the chemical structure of PEI to maximize its adjuvanticity and decrease its toxicity remains a challenge. Here we show that the chemical structure of PEI strongly influences how well nanocomplexes of PEI and mRNA migrate to the lymph nodes and elicit immune responses. Conjugating cyclodextrin (CD) with PEI600 or PEI2k yielded CP (CD-PEI) polymers with different CD/PEI ratios. We analyzed the delivery efficacy of CP600, CP2k, and PEI25k as intranasal mRNA vaccine carriers by evaluating the lymph nodes migration and immune responses. Among these polymers, CP2k/mRNA showed significantly higher in vitro transfection efficiency, stronger abilities to migrate to lymph nodes and stimulate dendritic cells maturation in vivo, which further led to potent humoral and cellular immune responses, and showed lower local and systemic toxicity than PEI25k/mRNA. These results demonstrate the potential of CD-PEI2k/mRNA nanocomplex as a self-adjuvanting vaccine delivery vehicle that traffics to lymph nodes with high efficiency. As we face outbreaks of pandemic diseases such as Zika virus, intranasal mRNA vaccination provides instant massive protection against highly variant viruses. Various polymer-based delivery systems have been successfully applied in intranasal vaccine delivery. However, the influence of molecular structure of the polymeric carriers on the lymph node trafficking and dendritic cell maturation is seldom studied for intranasal vaccination. Therefore, engineering polymer-based vaccine delivery system and elucidating the relationship between molecular structure and the intranasal delivery efficiency are essential for maximizing the immune responses. We hereby

Induction of CD8(+) T cell responses and protective efficacy following microneedle-mediated delivery of a live adenovirus-vectored malaria vaccine.

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Pearson, Frances E; O'Mahony, Conor; Moore, Anne C; Hill, Adrian V S

2015-06-22

There is an urgent need for improvements in vaccine delivery technologies. This is particularly pertinent for vaccination programmes within regions of limited resources, such as those required for adequate provision for disposal of used needles. Microneedles are micron-sized structures that penetrate the stratum corneum of the skin, creating temporary conduits for the needle-free delivery of drugs or vaccines. Here, we aimed to investigate immunity induced by the recombinant simian adenovirus-vectored vaccine ChAd63.ME-TRAP; currently undergoing clinical assessment as a candidate malaria vaccine, when delivered percutaneously by silicon microneedle arrays. In mice, we demonstrate that microneedle-mediated delivery of ChAd63.ME-TRAP induced similar numbers of transgene-specific CD8(+) T cells compared to intradermal (ID) administration with needle-and-syringe, following a single immunisation and after a ChAd63/MVA heterologous prime-boost schedule. When mice immunised with ChAd63/MVA were challenged with live Plasmodium berghei sporozoites, microneedle-mediated ChAd63.ME-TRAP priming demonstrated equivalent protective efficacy as did ID immunisation. Furthermore, responses following ChAd63/MVA immunisation correlated with a specific design parameter of the array used ('total array volume'). The level of transgene expression at the immunisation site and skin-draining lymph node (dLN) was also linked to total array volume. These findings have implications for defining silicon microneedle array design for use with live, vectored vaccines. Copyright © 2015 Elsevier Ltd. All rights reserved.

Combining different types of multifunctional liposomes loaded with ammonium bicarbonate to fabricate microneedle arrays as a vaginal mucosal vaccine adjuvant-dual delivery system (VADDS).

Science.gov (United States)

Wang, Ning; Zhen, Yuanyuan; Jin, Yiguang; Wang, Xueting; Li, Ning; Jiang, Shaohong; Wang, Ting

2017-01-28

To develop effective mucosal vaccines, two types of multifunctional liposomes, the mannosylated lipid A-liposomes (MLLs) with a size of 200nm and the stealth lipid A-liposomes (SLLs) of 50nm, both loaded with a model antigen and NH 4 HCO 3 , were fabricated together into microneedles, forming the proSLL/MLL-constituted microneedle array (proSMMA), which upon rehydration dissolved rapidly recovering the initial MLLs and SLLs. Mice vaccinated with proSMMAs by vaginal mucosa patching other than conventional intradermal administration established robust antigen-specific humoral and cellular immunity at both systemic and mucosal levels, especially, in the reproductive and intestinal ducts. Further exploration demonstrated that the MLLs reconstituted from the administered proSMMAs were mostly taken up by vaginal mucosal dendritic cells, whereas the recovered SLLs trafficked directly to draining lymph nodes wherein to be picked up by macrophages. Moreover, the antigens delivered by either liposomes were also cross-presented for MHC-I displaying by APCs thanks to lysosome escape and ROS (reactive oxygen species) stimulation, both of which occurred when lysosomal acidifying the liposome-released NH 4 HCO 3 into CO 2 and NH 4 + /NH 3 to rupture lysosomes by gas expansion and to cause ROS production by excessive ammonia induction, resulting in a mixed Th1/Th2 type response which was also promoted by liposomal lipid A via activation of TLR4. In addition, vaginal vaccination of the engineered HSV2 antigen gD-loaded proSMMAs successfully protected mice from the virus challenge. Thus, the proSMMAs are in fact a vaccine adjuvant-dual delivery system capable of eliciting robust humoral and cellular immunity against the invading pathogens, especially, the sexually transmitted ones. Copyright © 2016 Elsevier B.V. All rights reserved.

Clinical evaluation of a novel microneedle device for intradermal delivery of an influenza vaccine: are all delivery methods the same?

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Levin, Yotam; Kochba, Efrat; Kenney, Richard

2014-07-23

The skin provides the largest immune barrier to infection and is a readily accessible site for vaccination, although intradermal (ID) injection can be challenging. The MicronJet™ microneedle is a novel device that consistently injects antigens very close to the skin's dendritic cells. A dose-sparing ID injection study was conducted in 280 healthy adult volunteers using trivalent virosomal adjuvanted influenza vaccine. ID injection of 3 μg using the MicronJet™ was well tolerated and showed a statistically higher geometric mean fold rise than the same dose ID using a conventional needle (Mantoux technique) for the H1N1 and B strains or a 15 μg intramuscular (IM) injection for the H3N2 strain. Thus, the immune response appears to partially depend on the delivery device and route of injection. The MicronJet™ may allow dose-sparing, yet give a superior response in influenza vaccination and warrants further clinical evaluation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Live bacterial delivery systems for development of mucosal vaccines

NARCIS (Netherlands)

Thole, J.E.R.; Dalen, P.J. van; Havenith, C.E.G.; Pouwels, P.H.; Seegers, J.F.M.L.; Tielen, F.D.; Zee, M.D. van der; Zegers, N.D.; Shaw, M.

2000-01-01

By expression of foreign antigens in attenuated strains derived from bacterial pathogens and in non-pathogenic commensal bacteria, recombinant vaccines are being developed that aim to stimulate mucosal immunity. Recent advances in the pathogenesis and molecular biology of these bacteria have allowed

Gold nanocluster-based vaccines for dual-delivery of antigens and immunostimulatory oligonucleotides

Science.gov (United States)

Tao, Yu; Zhang, Yan; Ju, Enguo; Ren, Hui; Ren, Jinsong

2015-07-01

We here report a facile one-pot synthesis of fluorescent gold nanoclusters (AuNCs) via the peptide biomineralization method, which can elicit specific immunological responses. The as-prepared peptide-protected AuNCs (peptide-AuNCs) display strong red fluorescence, and more importantly, as compared to the peptide alone, the immune stimulatory ability of the resulting peptide-AuNCs can not only be retained, but can also be efficaciously enhanced. Moreover, through a dual-delivery of antigen peptides and cytosine-phosphate-guanine (CpG) oligodeoxynucleotides (ODNs), the as-prepared peptide-AuNC-CpG conjugates can also act as smart self-vaccines to assist in the generation of high immunostimulatory activity, and be applied as a probe for intracellular imaging. Both in vitro and in vivo studies provide strong evidence that the AuNC-based vaccines may be utilized as safe and efficient immunostimulatory agents that are able to prevent and/or treat a variety of ailments.We here report a facile one-pot synthesis of fluorescent gold nanoclusters (AuNCs) via the peptide biomineralization method, which can elicit specific immunological responses. The as-prepared peptide-protected AuNCs (peptide-AuNCs) display strong red fluorescence, and more importantly, as compared to the peptide alone, the immune stimulatory ability of the resulting peptide-AuNCs can not only be retained, but can also be efficaciously enhanced. Moreover, through a dual-delivery of antigen peptides and cytosine-phosphate-guanine (CpG) oligodeoxynucleotides (ODNs), the as-prepared peptide-AuNC-CpG conjugates can also act as smart self-vaccines to assist in the generation of high immunostimulatory activity, and be applied as a probe for intracellular imaging. Both in vitro and in vivo studies provide strong evidence that the AuNC-based vaccines may be utilized as safe and efficient immunostimulatory agents that are able to prevent and/or treat a variety of ailments. Electronic supplementary information (ESI

Oral Delivery of Probiotics Expressing Dendritic Cell-Targeting Peptide Fused with Porcine Epidemic Diarrhea Virus COE Antigen: A Promising Vaccine Strategy against PEDV.

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Wang, Xiaona; Wang, Li; Huang, Xuewei; Ma, Sunting; Yu, Meiling; Shi, Wen; Qiao, Xinyuan; Tang, Lijie; Xu, Yigang; Li, Yijing

2017-10-25

Porcine epidemic diarrhea virus (PEDV), an enteric coronavirus, is the causative agent of porcine epidemic diarrhea (PED) that damages intestinal epithelial cells and results in severe diarrhea and dehydration in neonatal suckling pigs with up to 100% mortality. The oral vaccine route is reported as a promising approach for inducing protective immunity against PEDV invasion. Furthermore, dendritic cells (DCs), professional antigen-presenting cells, link humoral and cellular immune responses for homeostasis of the intestinal immune environment. In this study, in order to explore an efficient oral vaccine against PEDV infection, a mucosal DC-targeting oral vaccine was developed using Lactobacillus casei to deliver the DC-targeting peptide (DCpep) fused with the PEDV core neutralizing epitope (COE) antigen. This probiotic vaccine could efficiently elicit secretory immunoglobulin A (SIgA)-based mucosal and immunoglobulin G (IgG)-based humoral immune responses via oral vaccination in vivo. Significant differences ( p targeting peptide fused with PEDV COE antigen. This mucosal DC-targeting oral vaccine delivery effectively enhances vaccine antigen delivery efficiency, providing a useful strategy to induce efficient immune responses against PEDV infection.

Evaluation of biocompatibility and administration site reactogenicity of polyanhydride-particle-based platform for vaccine delivery.

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Huntimer, Lucas; Ramer-Tait, Amanda E; Petersen, Latrisha K; Ross, Kathleen A; Walz, Katherine A; Wang, Chong; Hostetter, Jesse; Narasimhan, Balaji; Wannemuehler, Michael J

2013-02-01

Efficacy, purity, safety, and potency are important attributes of vaccines. Polyanhydride particles represent a novel class of vaccine adjuvants and delivery platforms that have demonstrated the ability to enhance the stability of protein antigens as well as elicit protective immunity against bacterial pathogens. This work aims to elucidate the biocompatibility, inflammatory reactions, and particle effects on mice injected with a 5 mg dose of polyanhydride nanoparticles via common parenteral routes (subcutaneous and intramuscular). Independent of polymer chemistry, nanoparticles more effectively disseminated away from the injection site as compared to microparticles, which exhibited a depot effect. Using fluorescent probes, the in vivo distribution of three formulations of nanoparticles, following subcutaneous administration, indicated migration away from the injection site. Less inflammation was observed at the injection sites of mice-administered nanoparticles as compared to Alum and incomplete Freund's adjuvant. Furthermore, histological evaluation revealed minimal adverse injection site reactions and minimal toxicological effects associated with the administration of nanoparticles at 30 days post-administration. Collectively, these results demonstrate that polyanhydride nanoparticles do not induce inflammation as a cumulative effect of particle persistence or degradation and are, therefore, a viable candidate for a vaccine delivery platform. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A cost comparison of introducing and delivering pneumococcal, rotavirus and human papillomavirus vaccines in Rwanda.

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Ngabo, Fidèle; Levin, Ann; Wang, Susan A; Gatera, Maurice; Rugambwa, Celse; Kayonga, Celestin; Donnen, Philippe; Lepage, Philippe; Hutubessy, Raymond

2015-12-16

Detailed cost evaluations of delivery of new vaccines such as pneumococcal conjugate, human papillomavirus (HPV), and rotavirus vaccines in low and middle-income countries are scarce. This paper differs from others by comparing the costs of introducing multiple vaccines in a single country and then assessing the financial and economic impact at the time and implications for the future. The objective of the analysis was to understand the introduction and delivery cost per dose or per child of the three new vaccines in Rwanda to inform domestic and external financial resource mobilization. Start-up, recurrent, and capital costs from a government perspective were collected in 2012. Since pneumococcal conjugate and HPV vaccines had already been introduced, cost data for those vaccines were collected retrospectively while prospective (projected) costing was done for rotavirus vaccine. The financial unit cost per fully immunized child (or girl for HPV vaccine) of delivering 3 doses of each vaccine (without costs related to vaccine procurement) was $0.37 for rotavirus (RotaTeq(®)) vaccine, $0.54 for pneumococcal (Prevnar(®)) vaccine in pre-filled syringes, and $10.23 for HPV (Gardasil (®)) vaccine. The financial delivery costs of Prevnar(®) and RotaTeq(®) were similar since both were delivered using existing health system infrastructure to deliver infant vaccines at health centers. The total financial cost of delivering Gardasil(®) was higher than those of the two infant vaccines due to greater resource requirements associated with creating a new vaccine delivery system in for a new target population of 12-year-old girls who have not previously been served by the existing routine infant immunization program. The analysis indicates that service delivery strategies have an important influence on costs of introducing new vaccines and costs per girl reached with HPV vaccine are higher than the other two vaccines because of its delivery strategy. Documented information

Edible vaccines: Current status and future

Directory of Open Access Journals (Sweden)

Lal P

2007-01-01

Full Text Available Edible vaccines hold great promise as a cost-effective, easy-to-administer, easy-to-store, fail-safe and socioculturally readily acceptable vaccine delivery system, especially for the poor developing countries. It involves introduction of selected desired genes into plants and then inducing these altered plants to manufacture the encoded proteins. Introduced as a concept about a decade ago, it has become a reality today. A variety of delivery systems have been developed. Initially thought to be useful only for preventing infectious diseases, it has also found application in prevention of autoimmune diseases, birth control, cancer therapy, etc. Edible vaccines are currently being developed for a number of human and animal diseases. There is growing acceptance of transgenic crops in both industrial and developing countries. Resistance to genetically modified foods may affect the future of edible vaccines. They have passed the major hurdles in the path of an emerging vaccine technology. Various technical obstacles, regulatory and non-scientific challenges, though all seem surmountable, need to be overcome. This review attempts to discuss the current status and future of this new preventive modality.

Ceramic drug-delivery devices.

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Lasserre, A; Bajpai, P K

1998-01-01

A variety of ceramics and delivery systems have been used to deliver chemicals, biologicals, and drugs at various rates for desired periods of time from different sites of implantation. In vitro and in vivo studies have shown that ceramics can successfully be used as drug-delivery devices. Matrices, inserts, reservoirs, cements, and particles have been used to deliver a large variety of therapeutic agents such as antibiotics, anticancer drugs, anticoagulants, analgesics, growth factors, hormones, steroids, and vaccines. In this article, the advantages and disadvantages of conventional drug-delivery systems and the different approaches used to deliver chemical and biological agents by means of ceramic systems will be reviewed.

Plant-made vaccine antigens and biopharmaceuticals.

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Daniell, Henry; Singh, Nameirakpam D; Mason, Hugh; Streatfield, Stephen J

2009-12-01

Plant cells are ideal bioreactors for the production and oral delivery of vaccines and biopharmaceuticals, eliminating the need for expensive fermentation, purification, cold storage, transportation and sterile delivery. Plant-made vaccines have been developed for two decades but none has advanced beyond Phase I. However, two plant-made biopharmaceuticals are now advancing through Phase II and Phase III human clinical trials. In this review, we evaluate the advantages and disadvantages of different plant expression systems (stable nuclear and chloroplast or transient viral) and their current limitations or challenges. We provide suggestions for advancing this valuable concept for clinical applications and conclude that greater research emphasis is needed on large-scale production, purification, functional characterization, oral delivery and preclinical evaluation.

Physician Knowledge and Attitudes About Hepatitis A and Current Practices Regarding Hepatitis A Vaccination Delivery.

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Nelson, Noele P; Allison, Mandy A; Lindley, Megan C; Brtnikova, Michaela; Crane, Lori A; Beaty, Brenda L; Hurley, Laura P; Kempe, Allison

2017-07-01

To assess physicians': 1) knowledge and attitudes about hepatitis A disease and hepatitis A (HepA) vaccine, 2) child care and school HepA vaccine mandates, 3) practices related to HepA vaccine delivery, 4) factors associated with strongly recommending HepA vaccine to all 1- to 2-year-olds, and 5) feasibility of implementing HepA catch-up vaccination at health maintenance visits. A national survey was conducted among representative networks of pediatricians and family medicine physicians (FMs) from March to June, 2014 via e-mail or mail on the basis of provider preference. Response rates were 81% (356 of 440) among pediatricians and 75% (348 of 464) among FMs. Less than 50% correctly identified that hepatitis A virus (HAV) infection is usually asymptomatic in young children and that morbidity from HAV disease increases with age. Ninety-two percent of pediatricians and 59% of FMs strongly recommend HepA vaccine for all 1- to 2-year-olds. In addition to practice specialty, belief that HepA vaccine is required for kindergarten enrollment was the most robust predictor of strong physician recommendation. Gaps in knowledge regarding HAV infection and hepatitis A recommendations and lack of a strong recommendation for routine HepA vaccination of young children among FMs likely contribute to suboptimal coverage. Closing knowledge gaps and addressing barriers that prevent all physicians from strongly recommending HepA vaccine to 1- to 2-year-olds could help increase HepA vaccine coverage and ultimately improve population protection against HAV infection. Published by Elsevier Inc.

The Relationship between Facility-Based Delivery and Infant Immunization in sub-Saharan Africa.

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Moyer, Cheryl A; Benyas, Dana; Rominski, Sarah

2016-06-01

This study explored the relationship between facility-based delivery and infant immunizations in sub-Saharan Africa, controlling for economic development indicators. Publically available data were collected and imported into Stata 11.0 for descriptive, correlation, and regression analyses. Facility delivery was significantly associated with full vaccination and BCG immunization in children aged 12-23 months. Facility delivery was associated with full vaccination (phealthcare system.

GM-CSF increases mucosal and systemic immunogenicity of an H1N1 influenza DNA vaccine administered into the epidermis of non-human primates.

Directory of Open Access Journals (Sweden)

Peter T Loudon

2010-06-01

Full Text Available The recent H5N1 avian and H1N1 swine-origin influenza virus outbreaks reaffirm that the threat of a world-wide influenza pandemic is both real and ever-present. Vaccination is still considered the best strategy for protection against influenza virus infection but a significant challenge is to identify new vaccine approaches that offer accelerated production, broader protection against drifted and shifted strains, and the capacity to elicit anti-viral immune responses in the respiratory tract at the site of viral entry. As a safe alternative to live attenuated vaccines, the mucosal and systemic immunogenicity of an H1N1 influenza (A/New Caledonia/20/99 HA DNA vaccine administered by particle-mediated epidermal delivery (PMED or gene gun was analyzed in rhesus macaques.Macaques were immunized at weeks 0, 8, and 16 using a disposable single-shot particle-mediated delivery device designed for clinical use that delivers plasmid DNA directly into cells of the epidermis. Significant levels of hemagglutination inhibiting (HI antibodies and cytokine-secreting HA-specific T cells were observed in the periphery of macaques following 1-3 doses of the PMED HA DNA vaccine. In addition, HA DNA vaccination induced detectable levels of HA-specific mucosal antibodies and T cells in the lung and gut-associated lymphoid tissues of vaccinated macaques. Importantly, co-delivery of a DNA encoding the rhesus macaque GM-CSF gene was found to significantly enhance both the systemic and mucosal immunogenicity of the HA DNA vaccine.These results provide strong support for the development of a particle-mediated epidermal DNA vaccine for protection against respiratory pathogens such as influenza and demonstrate, for the first time, the ability of skin-delivered GM-CSF to serve as an effective mucosal adjuvant for vaccine induction of immune responses in the gut and respiratory tract.

Mucosal vaccines: recent progress in understanding the natural barriers.

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Borges, Olga; Lebre, Filipa; Bento, Dulce; Borchard, Gerrit; Junginger, Hans E

2010-02-01

It has long been known that protection against pathogens invading the organism via mucosal surfaces correlates better with the presence of specific antibodies in local secretions than with serum antibodies. The most effective way to induce mucosal immunity is to administer antigens directly to the mucosal surface. The development of vaccines for mucosal application requires antigen delivery systems and immunopotentiators that efficiently facilitate the presentation of the antigen to the mucosal immune system. This review provides an overview of the events within mucosal tissues that lead to protective mucosal immune responses. The understanding of those biological mechanisms, together with knowledge of the technology of vaccines and adjuvants, provides guidance on important technical aspects of mucosal vaccine design. Not being exhaustive, this review also provides information related to modern adjuvants, including polymeric delivery systems and immunopotentiators.

Current state and challenges in developing oral vaccines.

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Vela Ramirez, Julia E; Sharpe, Lindsey A; Peppas, Nicholas A

2017-05-15

While vaccination remains the most cost effective strategy for disease prevention, communicable diseases persist as the second leading cause of death worldwide. There is a need to design safe, novel vaccine delivery methods to protect against unaddressed and emerging diseases. Development of vaccines administered orally is preferable to traditional injection-based formulations for numerous reasons including improved safety and compliance, and easier manufacturing and administration. Additionally, the oral route enables stimulation of humoral and cellular immune responses at both systemic and mucosal sites to establish broader and long-lasting protection. However, oral delivery is challenging, requiring formulations to overcome the harsh gastrointestinal (GI) environment and avoid tolerance induction to achieve effective protection. Here we address the rationale for oral vaccines, including key biological and physicochemical considerations for next-generation oral vaccine design. Copyright © 2017 Elsevier B.V. All rights reserved.

Overview on zein protein: a promising pharmaceutical excipient in drug delivery systems and tissue engineering.

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Labib, Gihan

2018-01-01

Natural pharmaceutical excipients have been applied extensively in the past decades owing to their safety and biocompatibility. Zein, a natural protein of plant origin offers great benefit over other synthetic polymers used in controlled drug and biomedical delivery systems. It was used in a variety of medical fields including pharmaceutical and biomedical drug targeting, vaccine, tissue engineering, and gene delivery. Being biodegradable and biocompatible, the current review focuses on the history and the medical application of zein as an attractive still promising biopolymer. Areas covered: The current review gives a broadscope on zein as a still promising protein excipient in different fields. Zein- based drug and biomedical delivery systems are discussed with special focus on current and potential application in controlled drug delivery systems, and tissue engineering. Expert opinion: Zein as a protein of natural origin can still be considered a promising polymer in the field of drug delivery systems as well as in tissue engineering. Although different researchers spotted light on zein application in different industrial fields extensively, the feasibility of its use in the field of drug delivery replenished by investigators in recent years has not yet been fully approached.

Immune response in domestic ducks following intradermal delivery of inactivated vaccine against H5N1 highly pathogenic avian influenza virus adjuvanted with oligodeoxynucleotides containing CpG motifs.

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Yuk, Seong-Su; Lee, Dong-Hun; Park, Jae-Keun; To, Eredene-Ochir; Kwon, Jung-Hoon; Noh, Jin-Yong; Gomis, Susantha; Song, Chang-Seon

2015-08-01

Ducks are a natural reservoir for H5N1 highly pathogenic avian influenza (HPAI) viruses, which produces a range of clinical outcomes from asymptomatic infections to severe disease with mortality. Vaccination against HPAI is one of the few methods available for controlling avian influenza virus (AIV) infection in domestic ducks; therefore, it is necessary to improve vaccine efficacy against HPAI in domestic ducks. However, few studies have focused on enhancing the immune response by testing alternative administration routes and adjuvants. While attempting to maximize the efficacy of a vaccine, it is important to select an appropriate vaccine delivery route and adjuvant to elicit an enhanced immune response. Although several studies have indicated that the vaccination of ducks against HPAI viruses has offered protection against lethal virus challenge, the immunogenicity of the vaccine still requires improvement. In this study, we characterized the immune response following a novel vaccination strategy against H5N1 HPAI virus in domestic ducks. Our novel intradermal delivery system and the application of the cytosine-phosphodiester-guanine (CpG) oligodeoxynucleotide (ODN) adjuvant allowed us to obtain information regarding the sustained vaccine immunity. Compared with the intramuscular route of vaccination, the intradermal route resulted in higher antibody titer as well as lower antibody deviation following secondary vaccination. In addition, the use of a CpG-ODN adjuvant had a dose-sparing effect on antibody titer. Furthermore, when a high dose of antigen was used, the CpG-ODN-adjuvanted vaccine maintained a high mean antibody titer. This data demonstrates that intradermal immunization combined with administration of CpG-ODN as an adjuvant may be a promising strategy for improving vaccine efficacy in domestic ducks. © 2015 Poultry Science Association Inc.

Enhancing the role of veterinary vaccines reducing zoonotic diseases of humans: Linking systems biology with vaccine development

Energy Technology Data Exchange (ETDEWEB)

Adams, Leslie G.; Khare, Sangeeta; Lawhon, Sara D.; Rossetti, Carlos A.; Lewin, Harris A.; Lipton, Mary S.; Turse, Joshua E.; Wylie, Dennis C.; Bai, Yu; Drake, Kenneth L.

2011-09-22

The aim of research on infectious diseases is their prevention, and brucellosis and salmonellosis as such are classic examples of worldwide zoonoses for application of a systems biology approach for enhanced rational vaccine development. When used optimally, vaccines prevent disease manifestations, reduce transmission of disease, decrease the need for pharmaceutical intervention, and improve the health and welfare of animals, as well as indirectly protecting against zoonotic diseases of people. Advances in the last decade or so using comprehensive systems biology approaches linking genomics, proteomics, bioinformatics, and biotechnology with immunology, pathogenesis and vaccine formulation and delivery are expected to enable enhanced approaches to vaccine development. The goal of this paper is to evaluate the role of computational systems biology analysis of host:pathogen interactions (the interactome) as a tool for enhanced rational design of vaccines. Systems biology is bringing a new, more robust approach to veterinary vaccine design based upon a deeper understanding of the host pathogen interactions and its impact on the host's molecular network of the immune system. A computational systems biology method was utilized to create interactome models of the host responses to Brucella melitensis (BMEL), Mycobacterium avium paratuberculosis (MAP), Salmonella enterica Typhimurium (STM), and a Salmonella mutant (isogenic *sipA, sopABDE2) and linked to the basis for rational development of vaccines for brucellosis and salmonellosis as reviewed by Adams et al. and Ficht et al. [1,2]. A bovine ligated ileal loop biological model was established to capture the host gene expression response at multiple time points post infection. New methods based on Dynamic Bayesian Network (DBN) machine learning were employed to conduct a comparative pathogenicity analysis of 219 signaling and metabolic pathways and 1620 gene ontology (GO) categories that defined the host

Dual recombinant Lactococcus lactis for enhanced delivery of DNA vaccine reporter plasmid pPERDBY.

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Yagnik, Bhrugu; Sharma, Drashya; Padh, Harish; Desai, Priti

2017-04-01

Food grade Lactococcus lactis has been widely used as an antigen and DNA delivery vehicle. We have previously reported the use of non-invasive L. lactis to deliver the newly constructed immunostimulatory DNA vaccine reporter plasmid, pPERDBY. In the present report, construction of dual recombinant L. lactis expressing internalin A of Listeria monocytogenes and harboring pPERDBY (LL InlA + pPERDBY) to enhance the efficiency of delivery of DNA by L. lactis is outlined. After confirmation and validation of LL InlA + pPERDBY, its DNA delivery potential was compared with previously developed non-invasive r- L. lactis::pPERDBY. The use of invasive L. lactis resulted in around threefold increases in the number of enhanced green fluorescent protein-expressing Caco-2 cells. These findings reinforce the prospective application of invasive strain of L. lactis for delivery of DNA/RNA and antigens. © 2017 The Societies and John Wiley & Sons Australia, Ltd.

Mucosal Immunity and Protective Efficacy of Intranasal Inactivated Influenza Vaccine Is Improved by Chitosan Nanoparticle Delivery in Pigs.

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Dhakal, Santosh; Renu, Sankar; Ghimire, Shristi; Shaan Lakshmanappa, Yashavanth; Hogshead, Bradley T; Feliciano-Ruiz, Ninoshkaly; Lu, Fangjia; HogenEsch, Harm; Krakowka, Steven; Lee, Chang Won; Renukaradhya, Gourapura J

2018-01-01

Annually, swine influenza A virus (SwIAV) causes severe economic loss to swine industry. Currently used inactivated SwIAV vaccines administered by intramuscular injection provide homologous protection, but limited heterologous protection against constantly evolving field viruses, attributable to the induction of inadequate levels of mucosal IgA and cellular immune responses in the respiratory tract. A novel vaccine delivery platform using mucoadhesive chitosan nanoparticles (CNPs) administered through intranasal (IN) route has the potential to elicit strong mucosal and systemic immune responses in pigs. In this study, we evaluated the immune responses and cross-protective efficacy of IN chitosan encapsulated inactivated SwIAV vaccine in pigs. Killed SwIAV H1N2 (δ-lineage) antigens (KAg) were encapsulated in chitosan polymer-based nanoparticles (CNPs-KAg). The candidate vaccine was administered twice IN as mist to nursery pigs. Vaccinates and controls were then challenged with a zoonotic and virulent heterologous SwIAV H1N1 (γ-lineage). Pigs vaccinated with CNPs-KAg exhibited an enhanced IgG serum antibody and mucosal secretory IgA antibody responses in nasal swabs, bronchoalveolar lavage (BAL) fluids, and lung lysates that were reactive against homologous (H1N2), heterologous (H1N1), and heterosubtypic (H3N2) influenza A virus strains. Prior to challenge, an increased frequency of cytotoxic T lymphocytes, antigen-specific lymphocyte proliferation, and recall IFN-γ secretion by restimulated peripheral blood mononuclear cells in CNPs-KAg compared to control KAg vaccinates were observed. In CNPs-KAg vaccinated pigs challenged with heterologous virus reduced severity of macroscopic and microscopic influenza-associated pulmonary lesions were observed. Importantly, the infectious SwIAV titers in nasal swabs [days post-challenge (DPC) 4] and BAL fluid (DPC 6) were significantly ( p  influenza nanovaccine may be an ideal candidate vaccine for use in pigs, and pig is a

Simultaneous approach using systemic, mucosal and transcutaneous routes of immunization for development of protective HIV-1 vaccines.

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Belyakov, I M; Ahlers, J D

2011-01-01

Mucosal tissues are major sites of HIV entry and initial infection. Induction of a local mucosal cytotoxic T lymphocyte response is considered an important goal in developing an effective HIV vaccine. In addition, activation and recruitment of memory CD4(+) and CD8(+) T cells in systemic lymphoid circulation to mucosal effector sites might provide the firewall needed to prevent virus spread. Therefore a vaccine that generates CD4(+) and CD8(+) responses in both mucosal and systemic tissues might be required for protection against HIV. However, optimal routes and number of vaccinations required for the generation of long lasting CD4(+) and CD8(+) CTL effector and memory responses are not well understood especially for mucosal T cells. A number of studies looking at protective immune responses against diverse mucosal pathogens have shown that mucosal vaccination is necessary to induce a compartmentalized immune response including maximum levels of mucosal high-avidity CD8(+) CTL, antigen specific mucosal antibodies titers (especially sIgA), as well as induction of innate anti-viral factors in mucosa tissue. Immune responses are detectable at mucosal sites after systemic delivery of vaccine, and prime boost regimens can amplify the magnitude of immune responses in mucosal sites and in systemic lymphoid tissues. We believe that the most optimal mucosal and systemic HIV/SIV specific protective immune responses and innate factors might best be achieved by simultaneous mucosal and systemic prime and boost vaccinations. Similar principals of vaccination may be applied for vaccine development against cancer and highly invasive pathogens that lead to chronic infection.

Laser-induced capillary leakage for blood biomarker detection and vaccine delivery via the skin.

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Wu, Jeffrey H; Li, Bo; Wu, Mei X

2016-07-01

Circulation system is the center for coordination and communication of all organs in our body. Examination of any change in its analytes or delivery of therapeutic drugs into the system consists of important medical practice in today's medicine. Two recent studies prove that brief illumination of skin with a low powered laser, at wavelengths preferentially absorbed by hemoglobin, increases the amount of circulating biomarkers in the epidermis and upper dermis by more than 1,000-fold. When probe-coated microneedle arrays are applied into laser-treated skin, plasma blood biomarkers can be reliably, accurately, and sufficiently quantified in 15∼30 min assays, with a maximal detection in one hr in a manner independent of penetration depth or a molecular mass of the biomarker. Moreover, the laser treatment permits a high efficient delivery of radiation-attenuated malarial sporozoites (RAS) into the circulation, leading to robust immunity against malaria infections, whereas similar immunization at sham-treated skin elicits poor immune responses. Thus this technology can potentially instruct designs of small, portable devices for onsite, in mobile clinics, or at home for point-of-care diagnosis and drug/vaccine delivery via the skin. Laser-induced capillary leakage (a) to induce extravasation of circualing molecules only (b) or facilitate entry of attenuated malaria sporozoites into the capillary (c). Skin illumination with a laser preferably absorbed by hemoglobin causes dilation of the capillary beneath the skin. The extravasated molecules can be sufficiently measured in the skin or guide sporozoites to enter the vessel. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Progress towards development of an HIV vaccine: report of the AIDS Vaccine 2009 Conference.

Science.gov (United States)

Ross, Anna Laura; Bråve, Andreas; Scarlatti, Gabriella; Manrique, Amapola; Buonaguro, Luigi

2010-05-01

The search for an HIV/AIDS vaccine is steadily moving ahead, generating and validating new concepts in terms of novel vectors for antigen delivery and presentation, new vaccine and adjuvant strategies, alternative approaches to design HIV-1 antigens for eliciting protective cross-neutralising antibodies, and identification of key mechanisms in HIV infection and modulation of the immune system. All these different perspectives are contributing to the unprecedented challenge of developing a protective HIV-1 vaccine. The high scientific value of this massive effort is its great impact on vaccinology as a whole, providing invaluable scientific information for the current and future development of new preventive vaccine as well as therapeutic knowledge-based infectious-disease and cancer vaccines. Copyright 2010 Elsevier Ltd. All rights reserved.

Recombinant vaccines and the development of new vaccine strategies

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Nascimento, I.P.; Leite, L.C.C. [Centro de Biotecnologia, Instituto Butantan, São Paulo, SP (Brazil)

2012-09-07

Vaccines were initially developed on an empirical basis, relying mostly on attenuation or inactivation of pathogens. Advances in immunology, molecular biology, biochemistry, genomics, and proteomics have added new perspectives to the vaccinology field. The use of recombinant proteins allows the targeting of immune responses focused against few protective antigens. There are a variety of expression systems with different advantages, allowing the production of large quantities of proteins depending on the required characteristics. Live recombinant bacteria or viral vectors effectively stimulate the immune system as in natural infections and have intrinsic adjuvant properties. DNA vaccines, which consist of non-replicating plasmids, can induce strong long-term cellular immune responses. Prime-boost strategies combine different antigen delivery systems to broaden the immune response. In general, all of these strategies have shown advantages and disadvantages, and their use will depend on the knowledge of the mechanisms of infection of the target pathogen and of the immune response required for protection. In this review, we discuss some of the major breakthroughs that have been achieved using recombinant vaccine technologies, as well as new approaches and strategies for vaccine development, including potential shortcomings and risks.

Recombinant vaccines and the development of new vaccine strategies

Directory of Open Access Journals (Sweden)

I.P. Nascimento

2012-12-01

Full Text Available Vaccines were initially developed on an empirical basis, relying mostly on attenuation or inactivation of pathogens. Advances in immunology, molecular biology, biochemistry, genomics, and proteomics have added new perspectives to the vaccinology field. The use of recombinant proteins allows the targeting of immune responses focused against few protective antigens. There are a variety of expression systems with different advantages, allowing the production of large quantities of proteins depending on the required characteristics. Live recombinant bacteria or viral vectors effectively stimulate the immune system as in natural infections and have intrinsic adjuvant properties. DNA vaccines, which consist of non-replicating plasmids, can induce strong long-term cellular immune responses. Prime-boost strategies combine different antigen delivery systems to broaden the immune response. In general, all of these strategies have shown advantages and disadvantages, and their use will depend on the knowledge of the mechanisms of infection of the target pathogen and of the immune response required for protection. In this review, we discuss some of the major breakthroughs that have been achieved using recombinant vaccine technologies, as well as new approaches and strategies for vaccine development, including potential shortcomings and risks.

Recombinant vaccines and the development of new vaccine strategies

International Nuclear Information System (INIS)

Nascimento, I.P.; Leite, L.C.C.

2012-01-01

Vaccines were initially developed on an empirical basis, relying mostly on attenuation or inactivation of pathogens. Advances in immunology, molecular biology, biochemistry, genomics, and proteomics have added new perspectives to the vaccinology field. The use of recombinant proteins allows the targeting of immune responses focused against few protective antigens. There are a variety of expression systems with different advantages, allowing the production of large quantities of proteins depending on the required characteristics. Live recombinant bacteria or viral vectors effectively stimulate the immune system as in natural infections and have intrinsic adjuvant properties. DNA vaccines, which consist of non-replicating plasmids, can induce strong long-term cellular immune responses. Prime-boost strategies combine different antigen delivery systems to broaden the immune response. In general, all of these strategies have shown advantages and disadvantages, and their use will depend on the knowledge of the mechanisms of infection of the target pathogen and of the immune response required for protection. In this review, we discuss some of the major breakthroughs that have been achieved using recombinant vaccine technologies, as well as new approaches and strategies for vaccine development, including potential shortcomings and risks

A non-pathogenic live vector as an efficient delivery system in vaccine design for the prevention of HPV16 E7-overexpressing cancers.

Science.gov (United States)

Hosseinzadeh, Sahar; Bolhassani, Azam; Rafati, Sima; Taheri, Tahereh; Zahedifard, Farnaz; Daemi, Amin; Taslimi, Yasaman; Hashemi, Mehrdad; Memarnejadian, Arash

2013-01-01

The attenuated or non-pathogenic live vectors have been evolved specifically to deliver DNA into cells as efficient delivery tools in gene therapy. Recently, a non-pathogenic protozoan, Leishmania tarentolae (L.tar) has attracted a great attention. In current study, we used Leishmania expression system (LEXSY) for stable expression of HPV16 E7 linked to different mini-chaperones [N-/C-terminal of gp96] and compared their immunogenicity and protective effects in C57BL/6 mice against TC-1 challenge. TC-1 murine model is primary C57BL/6 mice lung epithelial cells co-transformed with HPV16 E6, HPV16 E7 and ras oncogenes. Our results showed that subcutaneous administration of mice with both the recombinant L.tar-E7-NT (gp96) and L.tar-E7-CT (gp96) led to enhance the levels of IFN-γ and also IgG2a before and after challenge with TC-1. Furthermore, L.tar-E7-CT (gp96) live vaccine indicated significant protective effects as compared to control groups as well as group vaccinated with L.tar-E7. Indeed, the recombinant live vector is capable of eliciting effective humoral and cellular immune responses in mice, but however, further studies are required to increase their efficacy.

Challenges in immunisation service delivery for refugees in Australia: A health system perspective.

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Mahimbo, A; Seale, H; Smith, M; Heywood, A

2017-09-12

Refugees are at risk of being under-immunised in their countries of origin, in transit and post-resettlement in Australia. Whilst studies have focused on identifying barriers to accessibility of health services among refugees, few focus on providers' perspectives on immunisation service delivery to this group. Health service providers are well placed to provide insights into the pragmatic challenges associated with refugee health service delivery, which can be useful in identifying strategies aimed at improving immunisation coverage among this group. A qualitative study involving 30 semi-structured interviews was undertaken with key stakeholders in immunisation service delivery across all States and Territories in Australia between December 2014 and December 2015. Thematic analysis was undertaken. Variability in accessing program funding and vaccines, lack of a national policy for catch-up vaccination, unclear roles and responsibilities for catch-up, a lack of a central immunisation register and insufficient training among general practitioners were seen as the main challenges impacting on immunisation service delivery for refugees. This study provides insight into the challenges that impact on effective immunisation service delivery for refugees. Deliberate strategies such as national funding for relevant vaccines, improved data collection nationally and increased guidance for general practitioners on catch-up immunisation for refugees would help to ensure equitable access across all age groups. Copyright © 2017 Elsevier Ltd. All rights reserved.

Skin vaccination against cervical cancer associated human papillomavirus with a novel micro-projection array in a mouse model.

Directory of Open Access Journals (Sweden)

Holly J Corbett

Full Text Available BACKGROUND: Better delivery systems are needed for routinely used vaccines, to improve vaccine uptake. Many vaccines contain alum or alum based adjuvants. Here we investigate a novel dry-coated densely-packed micro-projection array skin patch (Nanopatch™ as an alternate delivery system to intramuscular injection for delivering an alum adjuvanted human papillomavirus (HPV vaccine (Gardasil® commonly used as a prophylactic vaccine against cervical cancer. METHODOLOGY/PRINCIPAL FINDINGS: Micro-projection arrays dry-coated with vaccine material (Gardasil® delivered to C57BL/6 mouse ear skin released vaccine within 5 minutes. To assess vaccine immunogenicity, doses of corresponding to HPV-16 component of the vaccine between 0.43 ± 0.084 ng and 300 ± 120 ng (mean ± SD were administered to mice at day 0 and day 14. A dose of 55 ± 6.0 ng delivered intracutaneously by micro-projection array was sufficient to produce a maximal virus neutralizing serum antibody response at day 28 post vaccination. Neutralizing antibody titres were sustained out to 16 weeks post vaccination, and, for comparable doses of vaccine, somewhat higher titres were observed with intracutaneous patch delivery than with intramuscular delivery with the needle and syringe at this time point. CONCLUSIONS/SIGNIFICANCE: Use of dry micro-projection arrays (Nanopatch™ has the potential to overcome the need for a vaccine cold chain for common vaccines currently delivered by needle and syringe, and to reduce risk of needle-stick injury and vaccine avoidance due to the fear of the needle especially among children.

Seasonal influenza vaccination during pregnancy and the risks of preterm delivery and small for gestational age birth.

Science.gov (United States)

Ahrens, Katherine A; Louik, Carol; Kerr, Stephen; Mitchell, Allen A; Werler, Martha M

2014-11-01

Influenza vaccination is routinely recommended for pregnant women, yet information on perinatal outcomes is sparse. We investigated the associations between trivalent (seasonal) influenza vaccination during pregnancy and the risks of preterm delivery (PTD, live birth vaccination and PTD and SGA were assessed using Cox and logistic regression models, respectively, with propensity scores used to adjust for confounding. Women vaccinated against pandemic H1N1 were excluded from the analysis. Influenza vaccination during pregnancy showed a near null association with PTD for influenza seasons 2006-07 through 2008-09 compared with unvaccinated women [adjusted hazard ratios (aHR) ranged from 0.79 [95% confidence interval (CI) 0.28, 2.21] in 2007-08 to 1.08 [95% CI: 0.40, 2.95] in 2008-09]. For 2009-10, the risk of PTD was higher in vaccinated women (aHR, 7.81 [95% CI: 2.66, 23.0]). Influenza vaccination was not associated with appreciable risks for SGA for all seasons with sufficient numbers of exposed SGA. Though limited by study size, these findings add support to previous observations of little or no increased risk of PTD or SGA associated with seasonal influenza vaccination for three of the four influenza seasons in our study. The increased risk of PTD observed for the 2009-10 influenza season warrants further investigation. © 2014 John Wiley & Sons Ltd.

Targeted Delivery of GP5 Antigen of PRRSV to M Cells Enhances the Antigen-Specific Systemic and Mucosal Immune Responses

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Luping Du

2018-01-01

Full Text Available Efficient delivery of antigens through oral immunization is a first and critical step for successful induction of mucosal immunity, which can provide protection against pathogens invading the mucosa. Membranous/microfold cells (M cells within the mucosa can transcytose internalized antigen without degradation and thus play an important role in initiating antigen-specific mucosal immune responses through inducing secretory IgA production. In this research, we modified poly (D, L-lactide-co-glycolide (PLGA nanoparticles (NPs with Ulex europaeus agglutinin 1 (UEA-1 and successfully prepared an oral vaccine delivery system, UEA-1/PLGA NPs. PLGA NPs were prepared using a standard double emulsion solvent evaporation technique, which can protect the entrapped PRRSV DNA vaccine [pcDNA3.1-SynORF5 (synthetic ORF5] or subunit vaccine ORF5-encoded glycoprotein (GP5 from exposure to the gastrointestinal (GI tract and release the plasmids in a controlled manner. With UEA-1 modification, the UEA-1/PLGA NPs can be effectively transported by M-cells. We investigated immune response induced by UEA-1/PLGA-SynORF5 or UEA-1/PLGA-GP5 following inoculation in mice and piglets. Compared with PLGA-SynORF5 or PLGA-GP5 NPs, UEA-1/PLGA-SynORF5, or UEA-1/PLGA-GP5 NPs stimulated significantly increased serum IgG levels and augmented intestinal IgA levels in mice and piglets (P < 0.05. Our findings indicate UEA-1/PLGA NPs can be applied as a promising and universally robust oral vaccine delivery system.

Targeted Delivery of GP5 Antigen of PRRSV to M Cells Enhances the Antigen-Specific Systemic and Mucosal Immune Responses

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Du, Luping; Yu, Zhengyu; Pang, Fengjiao; Xu, Xiangwei; Mao, Aihua; Yuan, Wanzhe; He, Kongwang; Li, Bin

2018-01-01

Efficient delivery of antigens through oral immunization is a first and critical step for successful induction of mucosal immunity, which can provide protection against pathogens invading the mucosa. Membranous/microfold cells (M cells) within the mucosa can transcytose internalized antigen without degradation and thus play an important role in initiating antigen-specific mucosal immune responses through inducing secretory IgA production. In this research, we modified poly (D, L-lactide-co-glycolide) (PLGA) nanoparticles (NPs) with Ulex europaeus agglutinin 1 (UEA-1) and successfully prepared an oral vaccine delivery system, UEA-1/PLGA NPs. PLGA NPs were prepared using a standard double emulsion solvent evaporation technique, which can protect the entrapped PRRSV DNA vaccine [pcDNA3.1-SynORF5 (synthetic ORF5)] or subunit vaccine ORF5-encoded glycoprotein (GP5) from exposure to the gastrointestinal (GI) tract and release the plasmids in a controlled manner. With UEA-1 modification, the UEA-1/PLGA NPs can be effectively transported by M-cells. We investigated immune response induced by UEA-1/PLGA-SynORF5 or UEA-1/PLGA-GP5 following inoculation in mice and piglets. Compared with PLGA-SynORF5 or PLGA-GP5 NPs, UEA-1/PLGA-SynORF5, or UEA-1/PLGA-GP5 NPs stimulated significantly increased serum IgG levels and augmented intestinal IgA levels in mice and piglets (P < 0.05). Our findings indicate UEA-1/PLGA NPs can be applied as a promising and universally robust oral vaccine delivery system. PMID:29423381

Bacillus subtilis as a tool for vaccine development: from antigen factories to delivery vectors

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Luís C.S. Ferreira

2005-03-01

Full Text Available Bacillus subtilis and some of its close relatives have a long history of industrial and biotechnological applications. Search for antigen expression systems based on recombinant B. subtilis strains sounds attractive both by the extensive genetic knowledge and the lack of an outer membrane, which simplify the secretion and purification of heterologous proteins. More recently, genetically modified B. subtilis spores have been described as indestructible delivery vehicles for vaccine antigens. Nonetheless both production and delivery of antigens by B. subtilis strains face some inherent obstacles, as unstable gene expression and reduced immunogenicity that, otherwise, can be overcome by already available gene technology approaches. In the present review we present the status of B. subtilis-based vaccine research, either as protein factories or delivery vectors, and discuss some alternatives for a better use of genetically modified strains.Bacillus subtilis e alguns de seus parentes mais próximos possuem uma longa história de aplicações industriais e biotecnológicas. A busca de sistemas de expressão de antígenos baseados em linhagens recombinants de B. subtilis mostra-se atrativa em função do conhecimento genético disponível e ausência de uma membrana externa, o que simplifica a secreção e a purificação de proteínas heterólogas. Mais recentemente, esporos geneticamente modificados de B. subtilis foram descritos com veículos indestrutíveis para o transporte de antígenos vacinais. Todavia a produção e o transporte de antígenos por linhagens de B. subtilis encontra obstáculos, como a expressão gênica instável e imunogenicidade reduzida, que podem ser superados com o auxílio de tecnologias genéticas atualmente disponíveis. Apresentamos nesta revisão o estado atual da pesquisa em vacinas baseadas em B. subtilis, empregado tanto como fábrica de proteínas ou veículos, e discute algumas alternativas para o uso mais

Mucosal Immunity and Protective Efficacy of Intranasal Inactivated Influenza Vaccine Is Improved by Chitosan Nanoparticle Delivery in Pigs

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Santosh Dhakal

2018-05-01

Full Text Available Annually, swine influenza A virus (SwIAV causes severe economic loss to swine industry. Currently used inactivated SwIAV vaccines administered by intramuscular injection provide homologous protection, but limited heterologous protection against constantly evolving field viruses, attributable to the induction of inadequate levels of mucosal IgA and cellular immune responses in the respiratory tract. A novel vaccine delivery platform using mucoadhesive chitosan nanoparticles (CNPs administered through intranasal (IN route has the potential to elicit strong mucosal and systemic immune responses in pigs. In this study, we evaluated the immune responses and cross-protective efficacy of IN chitosan encapsulated inactivated SwIAV vaccine in pigs. Killed SwIAV H1N2 (δ-lineage antigens (KAg were encapsulated in chitosan polymer-based nanoparticles (CNPs-KAg. The candidate vaccine was administered twice IN as mist to nursery pigs. Vaccinates and controls were then challenged with a zoonotic and virulent heterologous SwIAV H1N1 (γ-lineage. Pigs vaccinated with CNPs-KAg exhibited an enhanced IgG serum antibody and mucosal secretory IgA antibody responses in nasal swabs, bronchoalveolar lavage (BAL fluids, and lung lysates that were reactive against homologous (H1N2, heterologous (H1N1, and heterosubtypic (H3N2 influenza A virus strains. Prior to challenge, an increased frequency of cytotoxic T lymphocytes, antigen-specific lymphocyte proliferation, and recall IFN-γ secretion by restimulated peripheral blood mononuclear cells in CNPs-KAg compared to control KAg vaccinates were observed. In CNPs-KAg vaccinated pigs challenged with heterologous virus reduced severity of macroscopic and microscopic influenza-associated pulmonary lesions were observed. Importantly, the infectious SwIAV titers in nasal swabs [days post-challenge (DPC 4] and BAL fluid (DPC 6 were significantly (p < 0.05 reduced in CNPs-KAg vaccinates but not in KAg vaccinates when compared

Design and evaluate alginate nanoparticles as a protein delivery system

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Saraei, F.

2013-12-01

Full Text Available In recent years, encapsulation of drugs and antigens in hydrogels, specifically in calcium alginate particles, is an interesting and practical technique that was developed widespread. It is well known that alginate solution, under proper conditions, can form suitable nanoparticles as a promising carrier system, for vaccine delivery. The aim of this study was to synthesis alginate nanoparticles as protein carrier and to evaluate the influence of various factors on nanoparticles properties. Alginate nanoparticles were prepared by ionic gelation method. Briefly, various concentrations of CaCl2 were added to different concentrations of sodium alginate dropwisly by homogenizing magnetically at 1300 rpm. The effects of homogenization time and (- rate were investigated on nanoparticle feature. Nanoparticles were characterized for their morphology and size distribution. Evaluation of loading capacity and loading efficiency of nanoparticles were performed by using various concentration of BSA. The concentration of 0.3%w/v sodium alginate and 0.1%w/v CaCl2 solution, homogenization time 45 min and homogenization rate 1300 rpm were observed as suitable condition - to prepare optimized nanoparticles. It can be concluded that the properties of nanoparticles are strongly dependent on the physicochemical conditions. The optimum concentrations of alginate and CaCl2and appropriate condition led to forming desirable nanoparticles that can be used as carrier for drug and vaccine delivery.

Liposome-Based Adjuvants for Subunit Vaccines: Formulation Strategies for Subunit Antigens and Immunostimulators

DEFF Research Database (Denmark)

Schmidt, Signe Tandrup; Foged, Camilla; Korsholm, Karen Smith

2016-01-01

be classified into delivery systems or immunostimulators. Liposomes are versatile delivery systems for antigens, and they can carefully be customized towards desired immune profiles by combining them with immunostimulators and optimizing their composition, physicochemical properties and antigen-loading mode......The development of subunit vaccines has become very attractive in recent years due to their superior safety profiles as compared to traditional vaccines based on live attenuated or whole inactivated pathogens, and there is an unmet medical need for improved vaccines and vaccines against pathogens...... of immunostimulators and antigens, respectively, into liposomes, and the choice of immunostimulator should ideally be based on knowledge regarding the specific PRR expression profile of the target APCs. Here, we review state-of-the-art formulation approaches employed for the inclusion of immunostimulators and subunit...

Weakened Immune System and Adult Vaccination

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... Basics Adult Vaccination Resources for Healthcare Professionals Weakened Immune System and Adult Vaccination Recommend on Facebook Tweet Share ... people with health conditions such as a weakened immune system. If you have cancer or other immunocompromising conditions, ...

Addressing health inequalities in the delivery of the human papillomavirus vaccination programme: examining the role of the school nurse.

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Tammy Boyce

Full Text Available HPV immunisation of adolescent girls is expected to have a significant impact in the reduction of cervical cancer. UK The HPV immunisation programme is primarily delivered by school nurses. We examine the role of school nurses in delivering the HPV immunisation programme and their impact on minimising health inequalities in vaccine uptake.A rapid evidence assessment (REA and semi-structured interviews with health professionals were conducted and analysed using thematic analysis. 80 health professionals from across the UK are interviewed, primarily school nurses and HPV immunisation programme coordinators. The REA identified 2,795 articles and after analysis and hand searches, 34 relevant articles were identified and analysed. Interviews revealed that health inequalities in HPV vaccination uptake were mainly related to income and other social factors in contrast to published research which emphasises potential inequalities related to ethnicity and/or religion. Most school nurses interviewed understood local health inequalities and made particular efforts to target girls who did not attend or missed doses. Interviews also revealed maintaining accurate and consistent records influenced both school nurses' understanding and efforts to target inequalities in HPV vaccination uptake.Despite high uptake in the UK, some girls remain at risk of not being vaccinated with all three doses. School nurses played a key role in reducing health inequalities in the delivery of the HPV programme. Other studies identified religious beliefs and ethnicity as potentially influencing HPV vaccination uptake but interviews for this research found this appeared not to have occurred. Instead school nurses stated girls who were more likely to be missed were those not in education. Improving understanding of the delivery processes of immunisation programmes and this impact on health inequalities can help to inform solutions to increase uptake and address health inequalities

Microneedle-mediated vaccine delivery

NARCIS (Netherlands)

Maaden, Koen van der

2014-01-01

Conventional vaccines are administered intramuscularly or subcutaneously via hypodermic needles, causing pain and stress. Since the skin is a powerful immune organ, it is not surprising that intradermal injections result in potent immune responses. However, they are relatively difficult to perform

Self-Assembly DNA Polyplex Vaccine inside Dissolving Microneedles for High-Potency Intradermal Vaccination

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Liao, Jing-Fong; Lee, Jin-Ching; Lin, Chun-Kuang; Wei, Kuo-Chen; Chen, Pin-Yuan; Yang, Hung-Wei

2017-01-01

The strong immunogenicity induction is the powerful weapon to prevent the virus infections. This study demonstrated that one-step synthesis of DNA polyplex vaccine in microneedle (MN) patches can induce high immunogenicity through intradermal vaccination and increase the vaccine stability for storage outside the cold chain. More negative charged DNA vaccine was entrapped into the needle region of MNs followed by DNA polyplex formation with branched polyethylenimine (bPEI) pre-coated in the cavities of polydimethylsiloxane (PDMS) molds that can deliver more DNA vaccine to immune-cell rich epidermis with high transfection efficiency. Our data in this study support the safety and immunogenicity of the MN-based vaccine; the MN patch delivery system induced an immune response 3.5-fold as strong as seen with conventional intramuscular administration; the DNA polyplex formulation provided excellent vaccine stability at high temperature (could be stored at 45ºC for at least 4 months); the DNA vaccine is expected to be manufactured at low cost and not generate sharps waste. We think this study is significant to public health because there is a pressing need for an effective vaccination in developing countries. PMID:28819449

TRANSDERMAL DRUG DELIVERY SYSTEM: REVIEW

OpenAIRE

Vishvakarama Prabhakar; Agarwal Shivendra; Sharma Ritika; Saurabh Sharma

2012-01-01

Various new technologies have been developed for the transdermal delivery of some important drugs. Today about 74% of drugs are taken orally and are found not to be as effective as desired. To improve such characters transdermal drug delivery system was emerged. Drug delivery through the skin to achieve a systemic effect of a drug is commonly known as transdermal drug delivery and differs from traditional topical drug delivery. Transdermal drug delivery systems (TDDS) are dosage forms involve...

Comparative performance of public and private sector delivery of BCG vaccination: evidence from Sub-Saharan Africa.

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Wagner, Zachary; Szilagyi, Peter G; Sood, Neeraj

2014-07-31

The private sector is an important source of health care in the developing world. However, there is limited evidence on how private providers compare to public providers, particularly for preventive services such as immunizations. We used data from Sub-Saharan Africa (SSA) to assess public-private differences in Bacillus Calmette-Guérin (BCG) vaccine delivery. We used demographic and health surveys from 102,629 children aged 0-59 months from 29 countries across SSA to measure differences in BCG status for children born at private versus public health facilities (BCG is recommended at birth). We used a probit model to estimate public-private differences in BCG delivery, while controlling for key confounders. Next, we estimated how differences in BCG status evolved over time for children born at private versus public facilities. Finally, we estimated heterogeneity in public-private differences based on wealth and rural-urban residency. We found that children born at a private facility were 7.1 percentage points less likely to receive BCG vaccine in the same month as birth than children born at a public facility (95% CI 6.3-8.0; pprivate providers (as opposed to NGOs) where the BCG provision rate was 10.0 percentage points less than public providers (95% CI 9.0-11.2; pprivate for-profit facilities remained less likely to be vaccinated up to 59 months after birth. Finally, public-private differences were more pronounced for poorer children and children in rural areas. The for-profit private sector performed substantially worse than the public sector in providing BCG vaccine to newborns, resulting in a longer duration of vulnerability to tuberculosis. This disparity was greater for poorer children and children in rural areas. Copyright © 2014 Elsevier Ltd. All rights reserved.

UAV Delivery Monitoring System

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San Khin Thida

2018-01-01

Full Text Available UAV-based delivery systems are increasingly being used in the logistics field, particularly to achieve faster last-mile delivery. This study develops a UAV delivery system that manages delivery order assignments, autonomous flight operation, real time control for UAV flights, and delivery status tracking. To manage the delivery item assignments, we apply the concurrent scheduler approach with a genetic algorithm. The present paper describes real time flight data based on a micro air vehicle communication protocol (MAVLink. It also presents the detailed hardware components used for the field tests. Finally, we provide UAV component analysis to choose the suitable components for delivery in terms of battery capacity, flight time, payload weight and motor thrust ratio.

Chitosan-Poly (I:C-PADRE Based Nanoparticles as Delivery Vehicles for Synthetic Peptide Vaccines

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Jorge F. Correia-Pinto

2015-09-01

Full Text Available The safety and precision of peptide antigens has prompted the search for adjuvants capable of increasing the immune response against these intrinsically poorly immunogenic antigens. The integration of both immunostimulants and peptide antigens within nanometric delivery systems for their co-delivery to immune cells is a promising vaccination strategy. With this in mind, the potential synergistic effect of the immunostimulant poly (I:C (pIC and a T-Helper peptide (PADRE, integrated into a chitosan (CS based nanostructure, was explored. The value of this nanostructured combination of materials was assessed for a peptide antigen (1338aa derived from the HPV-16 L2 protein. These nanoparticles, produced by ionic gelation technique, exhibited a nanometric size (<300 nm, a high positive surface charge (>40 mV and high pIC association efficiency (>96%. They also showed capacity for the association of both the 1338aa and PADRE peptides. The influence of the presence of pIC and PADRE in the nanocomposition, as well as that of the peptide presentation form (encapsulated versus surface adsorbed on the antibody induction was evaluated in a preliminary in vivo study. The data obtained highlights the possibility to engineer nanoparticles through the rational combination of a number of adjuvant molecules together with the antigen.

Enhanced immune responses by skin vaccination with influenza subunit vaccine in young hosts.

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Koutsonanos, Dimitrios G; Esser, E Stein; McMaster, Sean R; Kalluri, Priya; Lee, Jeong-Woo; Prausnitz, Mark R; Skountzou, Ioanna; Denning, Timothy L; Kohlmeier, Jacob E; Compans, Richard W

2015-09-08

Skin has gained substantial attention as a vaccine target organ due to its immunological properties, which include a high density of professional antigen presenting cells (APCs). Previous studies have demonstrated the effectiveness of this vaccination route not only in animal models but also in adults. Young children represent a population group that is at high risk from influenza infection. As a result, this group could benefit significantly from influenza vaccine delivery approaches through the skin and the improved immune response it can induce. In this study, we compared the immune responses in young BALB/c mice upon skin delivery of influenza vaccine with vaccination by the conventional intramuscular route. Young mice that received 5 μg of H1N1 A/Ca/07/09 influenza subunit vaccine using MN demonstrated an improved serum antibody response (IgG1 and IgG2a) when compared to the young IM group, accompanied by higher numbers of influenza-specific antibody secreting cells (ASCs) in the bone marrow. In addition, we observed increased activation of follicular helper T cells and formation of germinal centers in the regional lymph nodes in the MN immunized group, rapid clearance of the virus from their lungs as well as complete survival, compared with partial protection observed in the IM-vaccinated group. Our results support the hypothesis that influenza vaccine delivery through the skin would be beneficial for protecting the high-risk young population from influenza infection. Copyright © 2015. Published by Elsevier Ltd.

Active surveillance for influenza vaccine adverse events: the integrated vaccine surveillance system.

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Newes-Adeyi, Gabriella; Greece, Jacey; Bozeman, Sam; Walker, Deborah Klein; Lewis, Faith; Gidudu, Jane

2012-02-01

We conducted a pilot study of the Integrated Vaccine Surveillance System (IVSS), a novel active surveillance system for monitoring influenza vaccine adverse events that could be used in mass vaccination settings. We recruited 605 adult vaccinees from a convenience sample of 12 influenza vaccine clinics conducted by public health departments of two U.S. metropolitan regions. Vaccinees provided daily reports on adverse reactions following immunization (AEFI) using an interactive voice response system (IVR) or the internet for 14 consecutive days following immunization. Followup with nonrespondents was conducted through computer-assisted telephone interviewing (CATI). Data on vaccinee reports were available real-time through a dedicated secure website. 90% (545) of vaccinees made at least one daily report and 49% (299) reported consecutively for the full 14-day period. 58% (315) used internet, 20% (110) IVR, 6% (31) CATI, and 16% (89) used a combination for daily reports. Of the 545 reporters, 339 (62%) reported one or more AEFI, for a total of 594 AEFIs reported. The majority (505 or 85%) of these AEFIs were mild symptoms. It is feasible to develop a system to obtain real-time data on vaccine adverse events. Vaccinees are willing to provide daily reports for a considerable time post vaccination. Offering multiple modes of reporting encourages high response rates. Study findings on AEFIs showed that the IVSS was able to exhibit the emerging safety profile of the 2008 seasonal influenza vaccine. Copyright © 2011 Elsevier Ltd. All rights reserved.

An oral vaccine against candidiasis generated by a yeast molecular display system.

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Shibasaki, Seiji; Aoki, Wataru; Nomura, Takashi; Miyoshi, Ayuko; Tafuku, Senji; Sewaki, Tomomitsu; Ueda, Mitsuyoshi

2013-12-01

Enolase 1 (Eno1p) of Candida albicans is an immunodominant antigen. However, conventional technologies for preparing an injectable vaccine require purification of the antigenic protein and preparation of an adjuvant. To develop a novel type of oral vaccine against candidiasis, we generated Saccharomyces cerevisiae cells that display the Eno1p antigen on their surfaces. Oral delivery of the engineered S. cerevisiae cells prolonged survival rate of mice that were subsequently challenged with C. albicans. Given that a vaccine produced using molecular display technology avoids the need for protein purification, this oral vaccine offers a promising alternative to the use of conventional and injectable vaccines for preventing a range of infectious diseases. © 2013 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

Evaluation of mucosal and systemic immune responses elicited by GPI-0100- adjuvanted influenza vaccine delivered by different immunization strategies.

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Heng Liu

Full Text Available Vaccines for protection against respiratory infections should optimally induce a mucosal immune response in the respiratory tract in addition to a systemic immune response. However, current parenteral immunization modalities generally fail to induce mucosal immunity, while mucosal vaccine delivery often results in poor systemic immunity. In order to find an immunization strategy which satisfies the need for induction of both mucosal and systemic immunity, we compared local and systemic immune responses elicited by two mucosal immunizations, given either by the intranasal (IN or the intrapulmonary (IPL route, with responses elicited by a mucosal prime followed by a systemic boost immunization. The study was conducted in BALB/c mice and the vaccine formulation was an influenza subunit vaccine supplemented with GPI-0100, a saponin-derived adjuvant. While optimal mucosal antibody titers were obtained after two intrapulmonary vaccinations, optimal systemic antibody responses were achieved by intranasal prime followed by intramuscular boost. The latter strategy also resulted in the best T cell response, yet, it was ineffective in inducing nose or lung IgA. Successful induction of secretory IgA, IgG and T cell responses was only achieved with prime-boost strategies involving intrapulmonary immunization and was optimal when both immunizations were given via the intrapulmonary route. Our results underline that immunization via the lungs is particularly effective for priming as well as boosting of local and systemic immune responses.

Evaluation of Mucosal and Systemic Immune Responses Elicited by GPI-0100- Adjuvanted Influenza Vaccine Delivered by Different Immunization Strategies

Science.gov (United States)

Liu, Heng; Patil, Harshad P.; de Vries-Idema, Jacqueline; Wilschut, Jan; Huckriede, Anke

2013-01-01

Vaccines for protection against respiratory infections should optimally induce a mucosal immune response in the respiratory tract in addition to a systemic immune response. However, current parenteral immunization modalities generally fail to induce mucosal immunity, while mucosal vaccine delivery often results in poor systemic immunity. In order to find an immunization strategy which satisfies the need for induction of both mucosal and systemic immunity, we compared local and systemic immune responses elicited by two mucosal immunizations, given either by the intranasal (IN) or the intrapulmonary (IPL) route, with responses elicited by a mucosal prime followed by a systemic boost immunization. The study was conducted in BALB/c mice and the vaccine formulation was an influenza subunit vaccine supplemented with GPI-0100, a saponin-derived adjuvant. While optimal mucosal antibody titers were obtained after two intrapulmonary vaccinations, optimal systemic antibody responses were achieved by intranasal prime followed by intramuscular boost. The latter strategy also resulted in the best T cell response, yet, it was ineffective in inducing nose or lung IgA. Successful induction of secretory IgA, IgG and T cell responses was only achieved with prime-boost strategies involving intrapulmonary immunization and was optimal when both immunizations were given via the intrapulmonary route. Our results underline that immunization via the lungs is particularly effective for priming as well as boosting of local and systemic immune responses. PMID:23936066

Peptide and protein delivery using new drug delivery systems.

Science.gov (United States)

Jain, Ashish; Jain, Aviral; Gulbake, Arvind; Shilpi, Satish; Hurkat, Pooja; Jain, Sanjay K

2013-01-01

Pharmaceutical and biotechnological research sorts protein drug delivery systems by importance based on their various therapeutic applications. The effective and potent action of the proteins/peptides makes them the drugs of choice for the treatment of numerous diseases. Major research issues in protein delivery include the stabilization of proteins in delivery devices and the design of appropriate target-specific protein carriers. Many efforts have been made for effective delivery of proteins/peptidal drugs through various routes of administrations for successful therapeutic effects. Nanoparticles made of biodegradable polymers such as poly lactic acid, polycaprolactone, poly(lactic-co-glycolic acid), the poly(fumaric-co-sebacic) anhydride chitosan, and modified chitosan, as well as solid lipids, have shown great potential in the delivery of proteins/peptidal drugs. Moreover, scientists also have used liposomes, PEGylated liposomes, niosomes, and aquasomes, among others, for peptidal drug delivery. They also have developed hydrogels and transdermal drug delivery systems for peptidal drug delivery. A receptor-mediated delivery system is another attractive strategy to overcome the limitation in drug absorption that enables the transcytosis of the protein across the epithelial barrier. Modification such as PEGnology is applied to various proteins and peptides of the desired protein and peptides also increases the circulating life, solubility and stability, pharmacokinetic properties, and antigenicity of protein. This review focuses on various approaches for effective protein/peptidal drug delivery, with special emphasis on insulin delivery.

Costs of vaccine programs across 94 low- and middle-income countries.

Science.gov (United States)

Portnoy, Allison; Ozawa, Sachiko; Grewal, Simrun; Norman, Bryan A; Rajgopal, Jayant; Gorham, Katrin M; Haidari, Leila A; Brown, Shawn T; Lee, Bruce Y

2015-05-07

communities. By projecting the full costs of immunization programs, our findings may aid to garner greater country and donor commitments toward adequate resource mobilization and efficient allocation. As service delivery costs have increasingly become the main driver of vaccination program costs, it is essential to pay additional consideration to health systems strengthening. Copyright © 2015 Elsevier Ltd. All rights reserved.

Cost of goods sold and total cost of delivery for oral and parenteral vaccine packaging formats.

Science.gov (United States)

Sedita, Jeff; Perrella, Stefanie; Morio, Matt; Berbari, Michael; Hsu, Jui-Shan; Saxon, Eugene; Jarrahian, Courtney; Rein-Weston, Annie; Zehrung, Darin

2018-03-14

Despite limitations of glass packaging for vaccines, the industry has been slow to implement alternative formats. Polymer containers may address many of these limitations, such as breakage and delamination. However, the ability of polymer containers to achieve cost of goods sold (COGS) and total cost of delivery (TCOD) competitive with that of glass containers is unclear, especially for cost-sensitive low- and lower-middle-income countries. COGS and TCOD models for oral and parenteral vaccine packaging formats were developed based on information from subject matter experts, published literature, and Kenya's comprehensive multiyear plan for immunization. Rotavirus and inactivated poliovirus vaccines (IPV) were used as representative examples of oral and parenteral vaccines, respectively. Packaging technologies evaluated included glass vials, blow-fill-seal (BFS) containers, preformed polymer containers, and compact prefilled auto-disable (CPAD) devices in both BFS and preformed formats. For oral vaccine packaging, BFS multi-monodose (MMD) ampoules were the least expensive format, with a COGS of $0.12 per dose. In comparison, oral single-dose glass vials had a COGS of $0.40. BFS MMD ampoules had the lowest TCOD of oral vaccine containers at $1.19 per dose delivered, and ten-dose glass vials had a TCOD of $1.61 per dose delivered. For parenteral vaccines, the lowest COGS was achieved with ten-dose glass vials at $0.22 per dose. In contrast, preformed CPAD devices had the highest COGS at $0.60 per dose. Ten-dose glass vials achieved the lowest TCOD of the parenteral vaccine formats at $1.56 per dose delivered. Of the polymer containers for parenteral vaccines, BFS MMD ampoules achieved the lowest TCOD at $1.89 per dose delivered, whereas preformed CPAD devices remained the most expensive format, at $2.25 per dose delivered. Given their potential to address the limitations of glass and reduce COGS and TCOD, polymer containers deserve further consideration as alternative

Childhood vaccination in informal urban settlements in Nairobi, Kenya: Who gets vaccinated?

Directory of Open Access Journals (Sweden)

Ettarh Remare R

2011-01-01

Full Text Available Abstract Background Recent trends in global vaccination coverage have shown increases with most countries reaching 90% DTP3 coverage in 2008, although pockets of undervaccination continue to persist in parts of sub-Saharan Africa particularly in the urban slums. The objectives of this study were to determine the vaccination status of children aged between 12-23 months living in two slums of Nairobi and to identify the risk factors associated with incomplete vaccination. Methods The study was carried out as part of a longitudinal Maternal and Child Health study undertaken in Korogocho and Viwandani slums of Nairobi. These slums host the Nairobi Urban Health and Demographic Surveillance System (NUHDSS run by the African Population and Health Research Centre (APHRC. All women from the NUHDSS area who gave birth since September 2006 were enrolled in the project and administered a questionnaire which asked about the vaccination history of their children. For the purpose of this study, we used data from 1848 children aged 12-23 months who were expected to have received all the WHO-recommended vaccinations. The vaccination details were collected during the first visit about four months after birth with follow-up visits repeated thereafter at four month intervals. Full vaccination was defined as receiving all the basic childhood vaccinations by the end of 24 months of life, whereas up-to-date (UTD vaccination referred to receipt of BCG, OPV 1-3, DTP 1-3, and measles vaccinations within the first 12 months of life. All vaccination data were obtained from vaccination cards which were sighted during the household visit as well as by recall from mothers. Multivariate models were used to identify the risk factors associated with incomplete vaccination. Results Measles coverage was substantially lower than that for the other vaccines when determined using only vaccination cards or in addition to maternal recall. Up-to-date (UTD coverage with all vaccinations

A baiting system for the oral rabies vaccination of wild foxes and skunks.

Science.gov (United States)

Johnston, D H; Voigt, D R

1982-01-01

A bait delivery system has been developed for red foxes and skunks in Ontario, Canada. A biomarker (Tetracycline HCl) is incorporated into a meatball in a plastic bag. Deposits of tetracycline in teeth are detected microscopically with ultra-violet illumination of undecalcified sections. Baits were dropped from aircraft at the rate of 35 per km2 and accepted by 70% of foxes and 60% of skunks in the test area. Trials of various strains of inactivated vaccines are in progress.

Gelatin nanoparticles enhance delivery of hepatitis C virus recombinant NS2 gene.

Science.gov (United States)

Sabet, Salwa; George, Marina A; El-Shorbagy, Haidan M; Bassiony, Heba; Farroh, Khaled Y; Youssef, Tareq; Salaheldin, Taher A

2017-01-01

Development of an effective non-viral vaccine against hepatitis C virus infection is of a great importance. Gelatin nanoparticles (Gel.NPs) have an attention and promising approach as a viable carrier for delivery of vaccine, gene, drug and other biomolecules in the body. The present study aimed to develop stable Gel.NPs conjugated with nonstructural protein 2 (NS2) gene of Hepatitis C Virus genotype 4a (HCV4a) as a safe and an efficient vaccine delivery system. Gel.NPs were synthesized and characterized (size: 150±2 nm and zeta potential +17.6 mv). NS2 gene was successfully cloned and expressed into E. coli M15 using pQE-30 vector. Antigenicity of the recombinant NS2 protein was confirmed by Western blotting to verify the efficiency of NS2 as a possible vaccine. Then NS2 gene was conjugated to gelatin nanoparticles and a successful conjugation was confirmed by labeling and imaging using Confocal Laser Scanning Microscope (CLSM). Interestingly, the transformation of the conjugated NS2/Gel.NPs complex into E. coli DH5-α was 50% more efficient than transformation with the gene alone. In addition, conjugated NS2/Gel.NPs with ratio 1:100 (w/w) showed higher transformation efficiency into E. coli DH5-α than the other ratios (1:50 and 2:50). Gel.NPs effectively enhanced the gene delivery in bacterial cells without affecting the structure of NS2 gene and could be used as a safe, easy, rapid, cost-effective and non-viral vaccine delivery system for HCV.

Mass vaccination with a new, less expensive oral cholera vaccine using public health infrastructure in India: the Odisha model.

Science.gov (United States)

Kar, Shantanu K; Sah, Binod; Patnaik, Bikash; Kim, Yang Hee; Kerketta, Anna S; Shin, Sunheang; Rath, Shyam Bandhu; Ali, Mohammad; Mogasale, Vittal; Khuntia, Hemant K; Bhattachan, Anuj; You, Young Ae; Puri, Mahesh K; Lopez, Anna Lena; Maskery, Brian; Nair, Gopinath B; Clemens, John D; Wierzba, Thomas F

2014-02-01

The substantial morbidity and mortality associated with recent cholera outbreaks in Haiti and Zimbabwe, as well as with cholera endemicity in countries throughout Asia and Africa, make a compelling case for supplementary cholera control measures in addition to existing interventions. Clinical trials conducted in Kolkata, India, have led to World Health Organization (WHO)-prequalification of Shanchol, an oral cholera vaccine (OCV) with a demonstrated 65% efficacy at 5 years post-vaccination. However, before this vaccine is widely used in endemic areas or in areas at risk of outbreaks, as recommended by the WHO, policymakers will require empirical evidence on its implementation and delivery costs in public health programs. The objective of the present report is to describe the organization, vaccine coverage, and delivery costs of mass vaccination with a new, less expensive OCV (Shanchol) using existing public health infrastructure in Odisha, India, as a model. All healthy, non-pregnant residents aged 1 year and above residing in selected villages of the Satyabadi block (Puri district, Odisha, India) were invited to participate in a mass vaccination campaign using two doses of OCV. Prior to the campaign, a de jure census, micro-planning for vaccination and social mobilization activities were implemented. Vaccine coverage for each dose was ascertained as a percentage of the censused population. The direct vaccine delivery costs were estimated by reviewing project expenditure records and by interviewing key personnel. The mass vaccination was conducted during May and June, 2011, in two phases. In each phase, two vaccine doses were given 14 days apart. Sixty-two vaccination booths, staffed by 395 health workers/volunteers, were established in the community. For the censused population, 31,552 persons (61% of the target population) received the first dose and 23,751 (46%) of these completed their second dose, with a drop-out rate of 25% between the two doses. Higher

Origins of the Children's Vaccine Initiative: the political foundations.

Science.gov (United States)

Muraskin, W

1996-06-01

The Children's Vaccine Initiative (CVI) was founded in 1990-91 as a means to revolutionize the way that vaccines were developed for the South. The system for the creation of vaccines was a dis-articulated one in which basic research, product development and delivery were handled by different, often insufficiently linked groups. The public sector was deeply involved in research and delivery but not the vital product development area. That area was left to the private sector which was increasingly driven by the needs to maximize profits. Potential vaccines for diseases found in the South, where a hard currency market was limited, were often left undeveloped. The CVI was designed to change that situation. The CVI hoped to exploit the discoveries of biotechnology and produce not only new and improved vaccines, but ultimately to work towards a single multi-antigen vaccine given near birth that would immunize children for life. This article deals with the events that directly led to the creation of the CVI, and to the political problems caused by organizational and national rivalries that the new venture faced from its inception.

Intranasal delivery of influenza subunit vaccine formulated with GEM particles as an adjuvant

NARCIS (Netherlands)

Saluja, Vinay; Amorij, Jean P; van Roosmalen, Maarten L; Leenhouts, Kees; Huckriede, Anke; Hinrichs, Wouter L J; Frijlink, Henderik W

Nasal administration of influenza vaccine has the potential to facilitate influenza control and prevention. However, when administered intranasally (i.n.), commercially available inactivated vaccines only generate systemic and mucosal immune responses if strong adjuvants are used, which are often

Improving skills and institutional capacity to strengthen adolescent immunisation programmes and health systems in African countries through HPV vaccine introduction

Directory of Open Access Journals (Sweden)

Carine Dochez

2017-12-01

Full Text Available Several African countries have recently introduced or are currently introducing the HPV vaccine, either nationwide or through demonstration projects, while some countries are planning for introduction. A collaborative project was developed to strengthen country adolescent immunisation programmes and health systems in the African Region, addressing unique public health considerations of HPV vaccination: adolescents as the primary target group, delivery platforms (e.g. school-based and facility based, socio-behavioural issues, and the opportunity to deliver other health interventions alongside HPV vaccination.Following a successful “taking-stock” meeting, a training programme was drafted to assist countries to strengthen the integration of adolescent health interventions using HPV vaccination as an entry point. Two workshops were conducted in the Eastern and Southern African Regions. All countries reported on progress made during a final joint symposium.Of the 20 countries invited to participate in either of the workshops and/or final symposium, 17 countries participated: Angola, Botswana, Ethiopia, Kenya, Malawi, Mauritius, Mozambique, Namibia, Rwanda, Seychelles, South Africa, South Sudan, Swaziland, Tanzania, Uganda, Zambia and Zimbabwe. Countries that are currently implementing HPV vaccination programmes, either nationally or through demonstration projects, reported varying degrees of integration with other adolescent health interventions. The most commonly reported adolescent health interventions alongside HPV vaccination include health education (including sexually transmitted infections, deworming and delivering of other vaccines like tetanus toxoid (TT or tetanus diphtheria (Td.The project has successfully (a established an African-based network that will advocate for incorporating the HPV vaccine into national immunisation programmes; (b created a platform for experience exchange and thereby contributed to novel ideas of

Effective cancer vaccine platform based on attenuated salmonella and a type III secretion system.

Science.gov (United States)

Xu, Xin; Hegazy, Wael A H; Guo, Linjie; Gao, Xiuhua; Courtney, Amy N; Kurbanov, Suhrab; Liu, Daofeng; Tian, Gengwen; Manuel, Edwin R; Diamond, Don J; Hensel, Michael; Metelitsa, Leonid S

2014-11-01

Vaccines explored for cancer therapy have been based generally on injectable vector systems used to control foreign infectious pathogens, to which the immune system evolved to respond naturally. However, these vectors may not be effective at presenting tumor-associated antigens (TAA) to the immune system in a manner that is sufficient to engender antitumor responses. We addressed this issue with a novel orally administered Salmonella-based vector that exploits a type III secretion system to deliver selected TAA in the cytosol of professional antigen-presenting cells in situ. A systematic comparison of candidate genes from the Salmonella Pathogenicity Island 2 (SPI2) locus was conducted in the vaccine design, using model antigens and a codon-optimized form of the human TAA survivin (coSVN), an oncoprotein that is overexpressed in most human cancers. In a screen of 20 SPI2 promoter:effector combinations, a PsifB::sseJ combination exhibited maximal potency for antigen translocation into the APC cytosol, presentation to CD8 T cells, and murine immunogenicity. In the CT26 mouse model of colon carcinoma, therapeutic vaccination with a lead PsifB::sseJ-coSVN construct (p8032) produced CXCR3-dependent infiltration of tumors by CD8 T cells, reversed the CD8:Treg ratio at the tumor site, and triggered potent antitumor activity. Vaccine immunogenicity and antitumor potency were enhanced by coadministration of the natural killer T-cell ligand 7DW8-5, which heightened the production of IL12 and IFNγ. Furthermore, combined treatment with p8032 and 7DW8-5 resulted in complete tumor regression in A20 lymphoma-bearing mice, where protective memory was demonstrated. Taken together, our results demonstrate how antigen delivery using an oral Salmonella vector can provide an effective platform for the development of cancer vaccines. ©2014 American Association for Cancer Research.

Formulation and delivery of dermal DNA vaccines

NARCIS (Netherlands)

van den Berg, J.H.

2009-01-01

DNA vaccination is an appealing strategy of active vaccination, leading to the intracellular production of the encoding antigen which results in an efficient activation of an antigen specific immune response. Intradermal DNA tattooing was recently developed as a simple and robust method to induce

Project delivery system (PDS)

CERN Document Server

2001-01-01

As business environments become increasingly competitive, companies seek more comprehensive solutions to the delivery of their projects. "Project Delivery System: Fourth Edition" describes the process-driven project delivery systems which incorporates the best practices from Total Quality and is aligned with the Project Management Institute and ISO Quality Standards is the means by which projects are consistently and efficiently planned, executed and completed to the satisfaction of clients and customers.

AIDS vaccine: Present status and future challenges

Directory of Open Access Journals (Sweden)

Nigam P

2006-01-01

Full Text Available Development of a preventive vaccine for HIV is the best hope of controlling the AIDS pandemic. HIV has, however, proved a difficult pathogen to vaccinate against because of its very high mutation rate and capability to escape immune responses. Neutralizing antibodies that can neutralize diverse field strains have so far proved difficult to induce. Adjuvanting these vaccines with cytokine plasmids and a "prime-boost," approach is being evaluated in an effort to induce both CTL and antibody responses and thereby have immune responses active against both infected cells and free viral particles, thereby necessitating fewer doses of recombinant protein to reach maximum antibodies titers. Although obstacles exist in evaluation of candidate HIV vaccines, evidence from natural history studies, new molecular tools in virology and immunology, new adjuvants, new gene expression systems, new antigen delivery systems, recent discoveries in HIV entry and pathogenesis, and promising studies of candidate vaccines in animal models have provided reasons to hope that developing a safe and effective AIDS vaccine is possible and within reach.

A paradigm for peptide vaccine delivery using viral epitopes encapsulated in degradable polymer hydrogel capsules.

Science.gov (United States)

Chong, Siow-Feng; Sexton, Amy; De Rose, Robert; Kent, Stephen J; Zelikin, Alexander N; Caruso, Frank

2009-10-01

We report on the use of degradable polymer capsules as carriers for the delivery of oligopeptide antigens to professional antigen presenting cells (APCs). To achieve encapsulation, oligopeptide sequences were covalently linked to a negatively charged carrier polymer via biodegradable linkages and the resulting conjugate was then adsorbed onto amine-functionalized silica particles. These peptide-coated particles were then used as templates for the layer-by-layer (LbL) deposition of thiolated poly(methacrylic acid) (PMA(SH)) and poly(vinylpyrrolidone) (PVPON) multilayers. Removal of the silica core and disruption of the hydrogen bonding between PMA(SH) and PVPON by altering the solution pH yielded disulfide-stabilized PMA capsules that retain the encapsulated cargo in an oxidative environment. In the presence of a natural reducing agent, glutathione, cleavage of the disulfide bonds causes release of the peptide from the capsules. The developed strategy provides control over peptide loading into polymer capsules and yields colloidally stable micron- and submicron-sized carriers with uniform size and peptide loading. The conjugation and encapsulation procedures were proven to be non-degrading to the peptide vaccines. The peptide-loaded capsules were successfully used to deliver their cargo to APCs and activate CD8 T lymphocytes in a non-human primate model of SIV infection ex vivo. The reported approach represents a novel paradigm in the delivery of peptide vaccines and other therapeutic agents.

Synthetic sustained gene delivery systems.

Science.gov (United States)

Agarwal, Ankit; Mallapragada, Surya K

2008-01-01

Gene therapy today is hampered by the need of a safe and efficient gene delivery system that can provide a sustained therapeutic effect without cytotoxicity or unwanted immune responses. Bolus gene delivery in solution results in the loss of delivered factors via lymphatic system and may cause undesired effects by the escape of bioactive molecules to distant sites. Controlled gene delivery systems, acting as localized depot of genes, provide an extended sustained release of genes, giving prolonged maintenance of the therapeutic level of encoded proteins. They also limit the DNA degradation in the nuclease rich extra-cellular environment. While attempts have been made to adapt existing controlled drug delivery technologies, more novel approaches are being investigated for controlled gene delivery. DNA encapsulated in nano/micro spheres of polymers have been administered systemically/orally to be taken up by the targeted tissues and provide sustained release once internalized. Alternatively, DNA entrapped in hydrogels or scaffolds have been injected/implanted in tissues/cavities as platforms for gene delivery. The present review examines these different modalities for sustained delivery of viral and non-viral gene-delivery vectors. Design parameters and release mechanisms of different systems made with synthetic or natural polymers are presented along with their prospective applications and opportunities for continuous development.

Colloidal drug delivery system: amplify the ocular delivery.

Science.gov (United States)

Ali, Javed; Fazil, Mohd; Qumbar, Mohd; Khan, Nazia; Ali, Asgar

2016-01-01

The ocular perceivers are the most voluntarily accessible organs in terms of location in the body, yet drug distribution to these tissues is one of the most intriguing and challenging endeavors and problematic to the pharmaceutical scientist. The most of ocular diseases are treated with topical application of conventional formulation, i.e. solutions, suspensions and ointment. Typically on installation of these conventional formulations, only <5% of the applied dose penetrates the cornea and reaches intraocular tissues, while a major fraction of the instilled dose is wastage due to the presence of many ocular barriers like external barriers, rapid loss of the instilled solution from the precorneal area and nasolacrimal drainage system. Systemic absorption caused systemic side effects varying from mild to life-threatening events. The main objective of this review is to explore the role of colloidal delivery of drug to minimize the drawbacks associated with them. This review provides an insight into the various constraints associated with ocular drug delivery, summarizes recent findings and applications of colloidal delivery systems, i.e. nanoparticles, nanosuspensions, liposomes, niosomes, dendrimers and contact lenses containing nanoparticles have the capacity to distribute ocular drugs to categorical target sites and hold promise to revolutionize the therapy of many ocular perceiver diseases and minimized the circumscription of conventional delivery. Form the basis of literature review, it has been found that the novel delivery system have greater impact to maximize ocular drug absorption, and minimize systemic absorption and side effects.

Vaccines and IP Rights: A Multifaceted Relationship.

Science.gov (United States)

Durell, Karen

2016-01-01

Just as there are many forms of vaccines and components to vaccines-particular compositions, delivery systems, components, and distribution networks-there are a variety of intellectual property (IP) protections applicable for vaccines. IP rights such as patent, copyright, trademarks, plant breeders' rights, and trade secrets may all be applicable to vaccines. Thus, discussion of IP rights and vaccines should not begin and end with the application of one IP right to a vaccine. The discussion should engage considerations of multiple IP rights applicable to a vaccine and how these can be utilized in an integrated manner in a strategy aimed at supporting the development and distribution of the vaccine. Such an approach to IP rights to vaccines allows for the integrated rights to be considered in light of the justifications for protecting vaccines with IP rights, as well as the issues relating to specific IP rights for vaccines, such as compulsory license regimes, available humanitarian purpose IP credits, etc. To view vaccines as the subject of multiple IP protections involves a refocusing, but the outcome can provide significant benefits for vaccine development and distribution.

Enhanced immunity in intradermal vaccination by novel hollow microneedles.

Science.gov (United States)

Ogai, N; Nonaka, I; Toda, Y; Ono, T; Minegishi, S; Inou, A; Hachiya, M; Fukamizu, H

2018-04-29

The intradermal (ID) route for vaccination represents an effective alternative to subcutaneous (SC)/intramuscular administration to induce protective immunity. However, a critical issue associated with ID vaccination is the precise delivery of solution in the upper dermis, which ensures enhanced immunity. We fabricated a hollow microneedle unit made of poly-glycolic acid by injection molding and bonding, and created a dedicated prototype injector. To ensure ID delivery of solution, the injected site was macroscopically and microscopically examined. Serum immunoglobulin G antibody production was measured by enzyme immunoassay and compared in groups of rats following either ID delivery with microneedles or SC administration with a 27-G stainless needle of graded vaccine doses. The unit used a tandem array of six microneedles, each with a side delivery hole, and a conduit inside for solution. Microneedles installed in the injector punctured the skin with the aid of a spring. Injection of solution formed a wheal due to ID distribution. Histologically, a wedge-shaped skin defect in the upper skin corresponded to each puncture site. Antibody titers following vaccinations on days 1 and 8 were significantly higher with ID injection than with SC delivery on day 15 and every 7 days thereafter until day 36 with mumps vaccination, and until day 36 with varicella vaccination. The microneedle unit presented here delivered solution intradermally without any difficulty and evoked antibody responses against viruses even with the reduced vaccine volume. Our findings confirm promising results of ID delivery as an immunogenic option to enhance vaccination efficacy. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Intranasal delivery of cationic PLGA nano/microparticles-loaded FMDV DNA vaccine encoding IL-6 elicited protective immunity against FMDV challenge.

Directory of Open Access Journals (Sweden)

Gang Wang

Full Text Available Mucosal vaccination has been demonstrated to be an effective means of eliciting protective immunity against aerosol infections of foot and mouth disease virus (FMDV and various approaches have been used to improve mucosal response to this pathogen. In this study, cationic PLGA (poly(lactide-co-glycolide nano/microparticles were used as an intranasal delivery vehicle as a means administering FMDV DNA vaccine encoding the FMDV capsid protein and the bovine IL-6 gene as a means of enhancing mucosal and systemic immune responses in animals. Three eukaryotic expression plasmids with or without bovine IL-6 gene (pc-P12A3C, pc-IL2AP12A3C and pc-P12AIL3C were generated. The two latter plasmids were designed with the IL-6 gene located either before or between the P12A and 3C genes, respectively, as a means of determining if the location of the IL-6 gene affected capsid assembly and the subsequent immune response. Guinea pigs and rats were intranasally vaccinated with the respective chitosan-coated PLGA nano/microparticles-loaded FMDV DNA vaccine formulations. Animals immunized with pc-P12AIL3C (followed by animals vaccinated with pc-P12A3C and pc-IL2AP12A3C developed the highest levels of antigen-specific serum IgG and IgA antibody responses and the highest levels of sIgA (secretory IgA present in mucosal tissues. However, the highest levels of neutralizing antibodies were generated in pc-IL2AP12A3C-immunized animals (followed by pc-P12AIL3C- and then in pc-P12A3C-immunized animals. pc-IL2AP12A3C-immunized animals also developed stronger cell mediated immune responses (followed by pc-P12AIL3C- and pc-P12A3C-immunized animals as evidenced by antigen-specific T-cell proliferation and expression levels of IFN-γ by both CD4+ and CD8+ splenic T cells. The percentage of animals protected against FMDV challenge following immunizations with pc-IL2AP12A3C, pc-P12AIL3C or pc-P12A3C were 3/5, 1/5 and 0/5, respectively. These data suggested that intranasal delivery

Strategies & recent development of transmission-blocking vaccines against Plasmodium falciparum

Directory of Open Access Journals (Sweden)

Neha Chaturvedi

2016-01-01

Full Text Available Transmission blocking malaria vaccines are aimed to block the development and maturity of sexual stages of parasite within mosquitoes. The vaccine candidate antigens (Pfs25, Pfs48/45, Pfs230 that have shown transmission blocking immunity in model systems are in different stages of development. These antigens are immunogenic with limited genetic diversity. Pfs25 is a leading candidate and currently in phase I clinical trial. Efforts are now focused on the cost-effective production of potent antigens using safe adjuvants and optimization of vaccine delivery system that are capable of inducing strong immune responses. This review addresses the potential usefulness, development strategies, challenges, clinical trials and current status of Plasmodium falciparum sexual stage malaria vaccine candidate antigens for the development of transmission-blocking vaccines.

Vaccines, our shared responsibility.

Science.gov (United States)

Pagliusi, Sonia; Jain, Rishabh; Suri, Rajinder Kumar

2015-05-05

The Developing Countries Vaccine Manufacturers' Network (DCVMN) held its fifteenth annual meeting from October 27-29, 2014, New Delhi, India. The DCVMN, together with the co-organizing institution Panacea Biotec, welcomed over 240 delegates representing high-profile governmental and nongovernmental global health organizations from 36 countries. Over the three-day meeting, attendees exchanged information about their efforts to achieve their shared goal of preventing death and disability from known and emerging infectious diseases. Special praise was extended to all stakeholders involved in the success of polio eradication in South East Asia and highlighted challenges in vaccine supply for measles-rubella immunization over the coming decades. Innovative vaccines and vaccine delivery technologies indicated creative solutions for achieving global immunization goals. Discussions were focused on three major themes including regulatory challenges for developing countries that may be overcome with better communication; global collaborations and partnerships for leveraging investments and enable uninterrupted supply of affordable and suitable vaccines; and leading innovation in vaccines difficult to develop, such as dengue, Chikungunya, typhoid-conjugated and EV71, and needle-free technologies that may speed up vaccine delivery. Moving further into the Decade of Vaccines, participants renewed their commitment to shared responsibility toward a world free of vaccine-preventable diseases. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Global challenges of implementing human papillomavirus vaccines

Directory of Open Access Journals (Sweden)

Mishra Amrita

2011-06-01

Full Text Available Abstract Human Papillomavirus vaccines are widely hailed as a sweeping pharmaceutical innovation for the universal benefit of all women. The implementation of the vaccines, however, is far from universal or equitable. Socio-economically marginalized women in emerging and developing, and many advanced economies alike, suffer a disproportionately large burden of cervical cancer. Despite the marketing of Human Papillomavirus vaccines as the solution to cervical cancer, the market authorization (licensing of the vaccines has not translated into universal equitable access. Vaccine implementation for vulnerable girls and women faces multiple barriers that include high vaccine costs, inadequate delivery infrastructure, and lack of community engagement to generate awareness about cervical cancer and early screening tools. For Human Papillomavirus vaccines to work as a public health solution, the quality-assured delivery of cheaper vaccines must be integrated with strengthened capacity for community-based health education and screening.

Technical Transformation of Biodefense Vaccines

Science.gov (United States)

Lu, Shan; Wang, Shixia

2013-01-01

Biodefense vaccines are developed against a diverse group of pathogens. Vaccines were developed for some of these pathogens a long time ago but they are facing new challenges to move beyond the old manufacturing technologies. New vaccines to be developed against other pathogens have to determine whether to follow traditional vaccination strategies or to seek new approaches. Advances in basic immunology and recombinant DNA technology have fundamentally transformed the process of formulating a vaccine concept, optimizing protective antigens, and selecting the most effective vaccine delivery approach for candidate biodefense vaccines. PMID:19837293

Evaluating the value proposition for improving vaccine thermostability to increase vaccine impact in low and middle-income countries.

Science.gov (United States)

Karp, Christopher L; Lans, Deborah; Esparza, José; Edson, Eleanore B; Owen, Katey E; Wilson, Christopher B; Heaton, Penny M; Levine, Orin S; Rao, Raja

2015-07-09

The need to keep vaccines cold in the face of high ambient temperatures and unreliable access to electricity is a challenge that limits vaccine coverage in low and middle-income countries (LMICs). Greater vaccine thermostability is generally touted as the obvious solution. Despite conventional wisdom, comprehensive analysis of the value proposition for increasing vaccine thermostability has been lacking. Further, while significant investments have been made in increasing vaccine thermostability in recent years, no vaccine products have been commercialized as a result. We analyzed the value proposition for increasing vaccine thermostability, grounding the analysis in specific vaccine use cases (e.g., use in routine immunization [RI] programs, or in campaigns) and in the broader context of cold chain technology and country level supply chain system design. The results were often surprising. For example, cold chain costs actually represent a relatively small fraction of total vaccine delivery system costs. Further, there are critical, vaccine use case-specific temporal thresholds that need to be overcome for significant benefits to be reaped from increasing vaccine thermostability. We present a number of recommendations deriving from this analysis that suggest a rational path toward unlocking the value (maximizing coverage, minimizing total system costs) of increased vaccine thermostability, including: (1) the full range of thermostability of existing vaccines should be defined and included in their labels; (2) for new vaccines, thermostability goals should be addressed up-front at the level of the target product profile; (3) improving cold chain infrastructure and supply chain system design is likely to have the largest impact on total system costs and coverage in the short term-and will influence the degree of thermostability required in the future; (4) in the long term, there remains value in monitoring the emergence of disruptive technologies that could remove the

Targeting vaccines to dendritic cells

DEFF Research Database (Denmark)

Foged, Camilla; Sundblad, Anne; Hovgaard, Lars

2002-01-01

delivery systems (DDS) with adjuvant effect that target DC directly and induce optimal immune responses. This paper will review the current knowledge of DC physiology as well as the progress in the field of novel vaccination strategies that directly or indirectly aim at targeting DC....... to be far superior to that of B-cells and macrophages. DC are localized at strategic places in the body at sites used by pathogens to enter the organism, and are thereby in an optimal position to capture antigens. In general, vaccination strategies try to mimic the invasiveness of the pathogens. DC...

Mechanism of action of mRNA-based vaccines.

Science.gov (United States)

Iavarone, Carlo; O'hagan, Derek T; Yu, Dong; Delahaye, Nicolas F; Ulmer, Jeffrey B

2017-09-01

The present review summarizes the growing body of work defining the mechanisms of action of this exciting new vaccine technology that should allow rational approaches in the design of next generation mRNA vaccines. Areas covered: Bio-distribution of mRNA, localization of antigen production, role of the innate immunity, priming of the adaptive immune response, route of administration and effects of mRNA delivery systems. Expert commentary: In the last few years, the development of RNA vaccines had a fast growth, the rising number of proof will enable rational approaches to improving the effectiveness and safety of this modern class of medicine.

Rotavirus vaccines: an overview.

OpenAIRE

Midthun, K; Kapikian, A Z

1996-01-01

Rotavirus vaccine development has focused on the delivery of live attenuated rotavirus strains by the oral route. The initial "Jennerian" approach involving bovine (RIT4237, WC3) or rhesus (RRV) rotavirus vaccine candidates showed that these vaccines were safe, well tolerated, and immunogenic but induced highly variable rates of protection against rotavirus diarrhea. The goal of a rotavirus vaccine is to prevent severe illness that can lead to dehydration in infants and young children in both...

Self-nanoemulsifying drug delivery systems for oral insulin delivery

DEFF Research Database (Denmark)

Li, Ping; Tan, Angel; Prestidge, Clive A

2014-01-01

This study aims at evaluating the combination of self-nanoemulsifying drug delivery systems (SNEDDS) and enteric-coated capsules as a potential delivery strategy for oral delivery of insulin. The SNEDDS preconcentrates, loaded with insulin-phospholipid complex at different levels (0, 2.5 and 10% w...

Factors affecting the implementation of childhood vaccination communication strategies in Nigeria: a qualitative study.

Science.gov (United States)

Oku, Afiong; Oyo-Ita, Angela; Glenton, Claire; Fretheim, Atle; Eteng, Glory; Ames, Heather; Muloliwa, Artur; Kaufman, Jessica; Hill, Sophie; Cliff, Julie; Cartier, Yuri; Bosch-Capblanch, Xavier; Rada, Gabriel; Lewin, Simon

2017-02-15

The role of health communication in vaccination programmes cannot be overemphasized: it has contributed significantly to creating and sustaining demand for vaccination services and improving vaccination coverage. In Nigeria, numerous communication approaches have been deployed but these interventions are not without challenges. We therefore aimed to explore factors affecting the delivery of vaccination communication in Nigeria. We used a qualitative approach and conducted the study in two states: Bauchi and Cross River States in northern and southern Nigeria respectively. We identified factors affecting the implementation of communication interventions through interviews with relevant stakeholders involved in vaccination communication in the health services. We also reviewed relevant documents. Data generated were transcribed verbatim and analysed using thematic analysis. We used the SURE framework to organise the identified factors (barriers and facilitators) affecting vaccination communication delivery. We then grouped these into health systems and community level factors. Some of the commonly reported health system barriers amongst stakeholders interviewed included: funding constraints, human resource factors (health worker shortages, training deficiencies, poor attitude of health workers and vaccination teams), inadequate infrastructure and equipment and weak political will. Community level factors included the attitudes of community stakeholders and of parents and caregivers. We also identified factors that appeared to facilitate communication activities. These included political support, engagement of traditional and religious institutions and the use of organised communication committees. Communication activities are a crucial element of immunization programmes. It is therefore important for policy makers and programme managers to understand the barriers and facilitators affecting the delivery of vaccination communication so as to be able to implement

Microcontainers as an oral delivery system for spray dried cubosomes containing ovalbumin

DEFF Research Database (Denmark)

Nielsen, Line Hagner; Rades, Thomas; Boyd, Ben

2017-01-01

The purpose of this study was to prepare cubosomes encapsulating the model antigen ovalbumin (OVA) via spray drying, and to characterise such cubosomes with a view for their potential application in oral vaccine delivery. Furthermore the cubosome formulation was loaded into polymeric...... microcontainers intended as an oral drug delivery system. The cubosomes consisted of commercial glyceryl monooleate, Dimodan®, containing OVA and were surrounded with a dextran shell prepared by spray drying. Cryo-TEM was used to confirm that cubosomes were formed after hydration of the spray dried precursor...... the cubosomes and microcontainers occurred at pH 6.8, releasing 44.1±5.6% of the OVA in 96h. Small-angle X-ray scattering (SAXS) revealed that the 'dry' particles possessed an internal ordered lipid structure (lamellar and inverse micellar phase) by virtue of a small amount of residual water, and after...

Chloroplast-derived vaccine antigens and biopharmaceuticals: protocols for expression, purification, or oral delivery and functional evaluation.

Science.gov (United States)

Singh, N Dolendro; Ding, Yi; Daniell, Henry

2009-01-01

Many vaccine antigens and biopharmaceutical proteins have been expressed at high levels via the chloroplast genome and their functionality has been evaluated using in vitro assays in cell cultures (i.e., macrophage lysis assay, inhibition of vesicular stomatitis virus-induced cytopathicity in baby hamster kidney cells, or inhibition of human HIV infection in TZM-BL cells) as well as protection after challenge with bacterial or viral pathogens or antitumor assays or delay the onset of insulitis in suitable animal models. Production of therapeutic proteins in chloroplasts eliminates the expensive fermentation technology. Moreover, oral delivery of chloroplast-derived therapeutic proteins eliminates expensive purification steps, cold storage, cold transportation, and delivery via sterile needles, thereby further decreasing their cost. In this chapter, we describe detailed protocols for chloroplast transformation including the construction of chloroplast transformation vectors, delivery of DNA into plant cells using particle bombardment, selection and regeneration of transformants by tissue culture, confirmation of transgene integration into the chloroplast genome and homoplasmy, evaluation of foreign gene expression, purification of foreign protein, or oral delivery via bioencapsulation, functional evaluation using in vitro and in vivo assays, and evaluation of immunity after challenge with pathogens in suitable animal models.

Animal vaccines based on orally presented yeast recombinants.

Science.gov (United States)

Shin, Min-Kyoung; Yoo, Han Sang

2013-09-13

In veterinary vaccinology, the oral route of administration is an attractive alternative compared to the commonly used parenteral route. Yeasts have a number of properties that make them potential live delivery systems for oral vaccination purposes such as their high expression levels, their GRAS status, adjuvant properties, and post-translational modification possibilities. Consequently, yeasts have been employed for the expression of heterologous genes and for the production of therapeutic proteins. Yeast-based vaccines are reviewed with regard to their ability to express and produce antigens from pathogens for veterinary use. Many of these vaccines have been shown to elicit protective immune responses following oral immunization in animals. Ultimately, yeast-based oral vaccines may offer a potential opportunity for the development of novel ideal vaccines in veterinary medicine. Copyright © 2013 Elsevier Ltd. All rights reserved.

Tailoring subunit vaccine immunity with adjuvant combinations and delivery routes using the Middle East respiratory coronavirus (MERS-CoV receptor-binding domain as an antigen.

Directory of Open Access Journals (Sweden)

Jiaming Lan

Full Text Available The development of an effective vaccine is critical for prevention of a Middle East respiratory syndrome coronavirus (MERS-CoV pandemic. Some studies have indicated the receptor-binding domain (RBD protein of MERS-CoV spike (S is a good candidate antigen for a MERS-CoV subunit vaccine. However, highly purified proteins are typically not inherently immunogenic. We hypothesised that humoral and cell-mediated immunity would be improved with a modification of the vaccination regimen. Therefore, the immunogenicity of a novel MERS-CoV RBD-based subunit vaccine was tested in mice using different adjuvant formulations and delivery routes. Different vaccination regimens were compared in BALB/c mice immunized 3 times intramuscularly (i.m. with a vaccine containing 10 µg of recombinant MERS-CoV RBD in combination with either aluminium hydroxide (alum alone, alum and polyriboinosinic acid (poly I:C or alum and cysteine-phosphate-guanine (CpG oligodeoxynucleotides (ODN. The immune responses of mice vaccinated with RBD, incomplete Freund's adjuvant (IFA and CpG ODN by a subcutaneous (s.c. route were also investigated. We evaluated the induction of RBD-specific humoral immunity (total IgG and neutralizing antibodies and cellular immunity (ELISpot assay for IFN-γ spot-forming cells and splenocyte cytokine production. Our findings indicated that the combination of alum and CpG ODN optimized the development of RBD-specific humoral and cellular immunity following subunit vaccination. Interestingly, robust RBD-specific antibody and T-cell responses were induced in mice immunized with the rRBD protein in combination with IFA and CpG ODN, but low level of neutralizing antibodies were elicited. Our data suggest that murine immunity following subunit vaccination can be tailored using adjuvant combinations and delivery routes. The vaccination regimen used in this study is promising and could improve the protection offered by the MERS-CoV subunit vaccine by eliciting

Global Vaccine and Immunization Research Forum: Opportunities and challenges in vaccine discovery, development, and delivery.

Science.gov (United States)

Ford, Andrew Q; Touchette, Nancy; Hall, B Fenton; Hwang, Angela; Hombach, Joachim

2016-03-18

The World Health Organization, the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, and the Bill & Melinda Gates Foundation convened the first Global Vaccine and Immunization Research Forum (GVIRF) in March 2014. This first GVIRF aimed to track recent progress of the Global Vaccine Action Plan research and development agenda, identify opportunities and challenges, promote partnerships in vaccine research, and facilitate the inclusion of all stakeholders in vaccine research and development. Leading scientists, vaccine developers, and public health officials from around the world discussed scientific and technical challenges in vaccine development, research to improve the impact of immunization, and regulatory issues. This report summarizes the discussions and conclusions from the forum participants. Copyright © 2016. Published by Elsevier Ltd.. All rights reserved.

Edible vaccines against veterinary parasitic diseases--current status and future prospects.

Science.gov (United States)

Jacob, Siju S; Cherian, Susan; Sumithra, T G; Raina, O K; Sankar, M

2013-04-08

Protection of domestic animals against parasitic infections remains a major challenge in most of the developing countries, especially in the surge of drug resistant strains. In this circumstance vaccination seems to be the sole practical strategy to combat parasites. Most of the presently available live or killed parasitic vaccines possess many disadvantages. Thus, expression of parasitic antigens has seen a continued interest over the past few decades. However, only a limited success was achieved using bacterial, yeast, insect and mammalian expression systems. This is witnessed by an increasing number of reports on transgenic plant expression of previously reported and new antigens. Oral delivery of plant-made vaccines is particularly attractive due to their exceptional advantages. Moreover, the regulatory burden for veterinary vaccines is less compared to human vaccines. This led to an incredible investment in the field of transgenic plant vaccines for veterinary purpose. Plant based vaccine trials have been conducted to combat various significant parasitic diseases such as fasciolosis, schistosomosis, poultry coccidiosis, porcine cycticercosis and ascariosis. Besides, passive immunization by oral delivery of antibodies expressed in transgenic plants against poultry coccidiosis is an innovative strategy. These trials may pave way to the development of promising edible veterinary vaccines in the near future. As the existing data regarding edible parasitic vaccines are scattered, an attempt has been made to assemble the available literature. Copyright © 2013 Elsevier Ltd. All rights reserved.

Viral vector-based influenza vaccines

Science.gov (United States)

de Vries, Rory D.; Rimmelzwaan, Guus F.

2016-01-01

ABSTRACT Antigenic drift of seasonal influenza viruses and the occasional introduction of influenza viruses of novel subtypes into the human population complicate the timely production of effective vaccines that antigenically match the virus strains that cause epidemic or pandemic outbreaks. The development of game-changing vaccines that induce broadly protective immunity against a wide variety of influenza viruses is an unmet need, in which recombinant viral vectors may provide. Use of viral vectors allows the delivery of any influenza virus antigen, or derivative thereof, to the immune system, resulting in the optimal induction of virus-specific B- and T-cell responses against this antigen of choice. This systematic review discusses results obtained with vectored influenza virus vaccines and advantages and disadvantages of the currently available viral vectors. PMID:27455345

Development and validation of an attenuated Mycoplasma hyopneumoniae aerosol vaccine.

Science.gov (United States)

Feng, Zhi-Xin; Wei, Yan-Na; Li, Gui-Lan; Lu, Xiao-Ming; Wan, Xiu-Feng; Pharr, G Todd; Wang, Zhan-Wei; Kong, Meng; Gan, Yuan; Bai, Fang-Fang; Liu, Mao-Jun; Xiong, Qi-Yan; Wu, Xu-Su; Shao, Guo-Qing

2013-12-27

Mycoplasma hyopneumoniae (M. hyopneumoniae) causes a chronic respiratory disease with high morbidity and low mortality in swine, and has been presented as a major cause of growth retardation in the swine industry. Aerosol vaccination presents a needle free, high throughput, and efficient platform for vaccine delivery, and has been widely applied in poultry vaccination. However, aerosol vaccines have rarely been used in swine vaccination primarily because the long and curving respiratory track of swine presents a barrier for vaccine particle delivery. To develop an effective M. hyopneumoniae aerosol vaccine, three major barriers need to be overcome: to optimize particle size for aerosol delivery, to maintain the viability of mycoplasma cells in the vaccine, and to optimize the environmental conditions for vaccine delivery. In this study, an aerosol mycoplasma vaccine was successfully developed based on a conventional live attenuated M. hyopneumoniae vaccine. Specifically, the Pari LCD nebulizer was used to produce an aerosol vaccine particle size less than 5 μm; and a buffer with 5% glycerol was developed and optimized to prevent inactivation of M. hyopneumoniae caused by aerosolization and evaporation. Before nebulization, the room temperature and relative humidity were control to 20-25 °C and 70-75%, respectively, which helped maintain the viability of aerosol vaccine. Animal experiments demonstrated that this newly developed aerosol vaccine was effectively delivered to swine low respiratory track, being confirmed by nested-PCR, in situ hybridization and scanning electron microscope. Moreover, M. hyopneumoniae specific sIgA secretion was detected in the nasal swab samples at 14 days post-immunization. To our knowledge, this is the first report on a live M. hyopneumoniae aerosol vaccine. Copyright © 2013 Elsevier B.V. All rights reserved.

CDC Wonder Vaccine Adverse Event Reporting System

Data.gov (United States)

U.S. Department of Health & Human Services — The Vaccine Adverse Event Reporting System (VAERS) online database on CDC WONDER provides counts and percentages of adverse event case reports after vaccination,...

Polymeric micro/nanoparticles: Particle design and potential vaccine delivery applications.

Science.gov (United States)

Yue, Hua; Ma, Guanghui

2015-11-04

Particle based adjuvant showed promising signs on delivering antigen to immune cells and acting as stimulators to elicit preventive or therapeutic response. Nevertheless, the wide size distribution of available polymeric particles has so far obscured the immunostimulative effects of particle adjuvant, and compromised the progress in pharmacological researches. To conquer this hurdle, our research group has carried out a series of researches regarding the particulate vaccine, by taking advantage of the successful fabrication of polymeric particles with uniform size. In this review, we highlight the insight and practical progress focused on the effects of physiochemical property (e.g. particle size, charge, hydrophobicity, surface chemical group, and particle shape) and antigen loading mode on the resultant biological/immunological outcome. The underlying mechanisms of how the particles-based vaccine functioned in the immune system are also discussed. Based on the knowledge, particles with high antigen payload and optimized attributes could be designed for expected adjuvant purpose, leading to the development of high efficient vaccine candidates. Copyright © 2015 Elsevier Ltd. All rights reserved.

Simulation of the cost-effectiveness of malaria vaccines

Directory of Open Access Journals (Sweden)

Tediosi Fabrizio

2009-06-01

Full Text Available Abstract Background A wide range of possible malaria vaccines is being considered and there is a need to identify which vaccines should be prioritized for clinical development. An important element of the information needed for this prioritization is a prediction of the cost-effectiveness of potential vaccines in the transmission settings in which they are likely to be deployed. This analysis needs to consider a range of delivery modalities to ensure that clinical development plans can be aligned with the most appropriate deployment strategies. Methods The simulations are based on a previously published individual-based stochastic model for the natural history and epidemiology of Plasmodium falciparum malaria. Three different vaccine types: pre-erythrocytic vaccines (PEV, blood stage vaccines (BSV, mosquito-stage transmission-blocking vaccines (MSTBV, and combinations of these, are considered each delivered via a range of delivery modalities (Expanded Programme of Immunization – EPI-, EPI with booster, and mass vaccination combined with EPI. The cost-effectiveness ratios presented are calculated for four health outcomes, for assumed vaccine prices of US$ 2 or US$ 10 per dose, projected over a 10-year period. Results The simulations suggest that PEV will be more cost-effective in low transmission settings, while BSV at higher transmission settings. Combinations of BSV and PEV are more efficient than PEV, especially in moderate to high transmission settings, while compared to BSV they are more cost-effective in moderate to low transmission settings. Combinations of MSTBV and PEV or PEV and BSV improve the effectiveness and the cost-effectiveness compared to PEV and BSV alone only when applied with EPI and mass vaccinations. Adding booster doses to the EPI is unlikely to be a cost-effective alternative to delivering vaccines via the EPI for any vaccine, while mass vaccination improves effectiveness, especially in low transmission settings, and is

Oral delivery of the Sj23LHD-GST antigen by Salmonella typhimurium type III secretion system protects against Schistosoma japonicum infection in mice.

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Guo Chen

2011-09-01

Full Text Available BACKGROUND: Schistosomiasis japonica is a zoonotic parasitic disease and oral vaccine delivery system would be benefit for prevention of this disease. Although attenuated salmonella has been used as an antigen expression vector for oral vaccine development, the membrane-bound vacuoles in which bacteria reside hinders the presentation of expressed heterologous antigens to the major histocompatibility complex (MHC molecules. The present work used an attenuated Salmonella typhimurium strain VNP20009 to secretory expression of Sj23LHDGST bivalent antigen from Schistosoma japonicum and tested the protective efficacy against S. japonicum infection in orally immunized mice. METHODOLOGY/PRINCIPAL FINDINGS: Promoters (nirB or pagC were used to express the antigen (Sj23LHDGST and the Salmonella type III or α-hemolysin secretion system was employed to secrete it. The immunoblotting analysis and fluorescent microscopy revealed that the antigen was effectively expressed and delivered to the cytosol of macrophages in vitro. Among recombinant vaccine strains, an engineered VNP20009 which expressed the antigen by nirB promoter and secreted it through type III secretion system (nirB-sopE(1-104-Sj23LHD-GST efficiently protected against S. japonicum infection in a mouse model. This strain elicited a predominantly IgG(2a antibody response and a markedly increase in the production of IL-12 and IFN-γ. The flow cytometric analysis demonstrated that this strain caused T cell activation as evidenced by significantly increased expression of CD44 and CD69. CONCLUSION/SIGNIFICANCE: Oral delivery of antigen by nirB-driven Salmonella typhimurium type III secretion system is a novel, safe, inexpensive, efficient and convenient approach for schistosome vaccine development.

A potential disruptive technology in vaccine development: gene-based vaccines and their application to infectious diseases.

Science.gov (United States)

Kaslow, David C

2004-10-01

Vaccine development requires an amalgamation of disparate disciplines and has unique economic and regulatory drivers. Non-viral gene-based delivery systems, such as formulated plasmid DNA, are new and potentially disruptive technologies capable of providing 'cheaper, simpler, and more convenient-to-use' vaccines. Typically and somewhat ironically, disruptive technologies have poorer product performance, at least in the near-term, compared with the existing conventional technologies. Because successful product development requires that the product's performance must meet or exceed the efficacy threshold for a desired application, the appropriate selection of the initial product applications for a disruptive technology is critical for its successful evolution. In this regard, the near-term successes of gene-based vaccines will likely be for protection against bacterial toxins and acute viral and bacterial infections. Recent breakthroughs, however, herald increasing rather than languishing performance improvements in the efficacy of gene-based vaccines. Whether gene-based vaccines ultimately succeed in eliciting protective immunity in humans to persistent intracellular pathogens, such as HIV, malaria and tuberculosis, for which the conventional vaccine technologies have failed, remains to be determined. A success against any one of the persistent intracellular pathogens would be sufficient proof that gene-based vaccines represent a disruptive technology against which future vaccine technologies will be measured.

Design and application of chitosan microspheres as oral and nasal vaccine carriers: an updated review

Directory of Open Access Journals (Sweden)

Islam MA

2012-12-01

Full Text Available Mohammad Ariful Islam,1–3,* Jannatul Firdous,1–3,* Yun-Jaie Choi,1 Cheol-Heui Yun,1–4 Chong-Su Cho1,21Department of Agricultural Biotechnology, 2Research Institute for Agriculture and Life Sciences, 3Center for Food and Bioconvergence, 4World Class University Biomodulation Program, Seoul National University, Seoul, South Korea*These authors contributed equally to this workAbstract: Chitosan, a natural biodegradable polymer, is of great interest in biomedical research due to its excellent properties including bioavailability, nontoxicity, high charge density, and mucoadhesivity, which creates immense potential for various pharmaceutical applications. It has gelling properties when it interacts with counterions such as sulfates or polyphosphates and when it crosslinks with glutaraldehyde. This characteristic facilitates its usefulness in the coating or entrapment of biochemicals, drugs, antigenic molecules as a vaccine candidate, and microorganisms. Therefore, chitosan together with the advance of nanotechnology can be effectively applied as a carrier system for vaccine delivery. In fact, chitosan microspheres have been studied as a promising carrier system for mucosal vaccination, especially via the oral and nasal route to induce enhanced immune responses. Moreover, the thiolated form of chitosan is of considerable interest due to its improved mucoadhesivity, permeability, stability, and controlled/extended release profile. This review describes the various methods used to design and synthesize chitosan microspheres and recent updates on their potential applications for oral and nasal delivery of vaccines. The potential use of thiolated chitosan microspheres as next-generation mucosal vaccine carriers is also discussed.Keywords: chitosan microspheres, oral, nasal, vaccine delivery, mucosal and systemic immune responses

Programmatic challenges in obtaining and confirming the pneumococcal vaccination status of cochlear implant recipients.

Science.gov (United States)

Carpenter, Ryan M; Limb, Charles J; Francis, Howard W; Gottschalk, Barbara; Niparko, John K

2010-10-01

Bacterial meningitis represents a substantial concern for individuals with cochlear implants (CIs). Chart review and direct patient and family correspondence to ascertain vaccination status. Information dissemination via brochure and electronic media, ongoing reminders of the importance of vaccination when confirmation of vaccination was not received. Marked improvement in vaccination rates ranging from 49% to 99% across different patient populations. Importantly, many patients received their vaccinations only after follow-up reminders. Ensuring optimal vaccination of all CI recipients against high-risk pathogens is a significantly challenging task. Maximizing vaccination rates in CI users will require an ongoing, active effort of information dissemination, documentation of compliance, and well-designed behavioral systems to streamline the pragmatic challenges in vaccination delivery.

Preparing and evaluating delivery systems for proteins

DEFF Research Database (Denmark)

Jorgensen, L; Moeller, E H; van de Weert, M

2006-01-01

From a formulation perspective proteins are complex and therefore challenging molecules to develop drug delivery systems for. The success of a formulation depends on the ability of the protein to maintain the native structure and activity during preparation and delivery as well as during shipping...... and long-term storage of the formulation. Therefore, the development and evaluation of successful and promising drug delivery systems is essential. In the present review, some of the particulate drug delivery systems for parenteral delivery of protein are presented and discussed. The challenge...... for incorporation of protein in particulate delivery systems is exemplified by water-in-oil emulsions....

Towards tailored vaccine delivery : Needs, challenges and perspectives

NARCIS (Netherlands)

Amorij, Jean-Pierre; Kersten, Gideon F. A.; Saluja, Vinay; Tonnis, Wouter F.; Hinrichs, Wouter L. J.; Slutter, Bram; Bal, Suzanne M.; Bouwstra, Joke A.; Huckriede, Anke; Jiskoot, Wim

2012-01-01

The ideal vaccine is a simple and stable formulation which can be conveniently administered and provides life-long immunity against a given pathogen. The development of such a vaccine, which should trigger broad and strong B-cell and T-cell responses against antigens of the pathogen in question, is

Towards tailored vaccine delivery: Needs, challenges and perspectives

NARCIS (Netherlands)

Amorij, Jean-Pierre; Kersten, Gideon F. A.; Saluja, Vinay; Tonnis, Wouter F.; Hinrichs, Wouter L. J.; Slütter, Bram; Bal, Suzanne M.; Bouwstra, Joke A.; Huckriede, Anke; Jiskoot, Wim

2012-01-01

The ideal vaccine is a simple and stable formulation which can be conveniently administered and provides life-long immunity against a given pathogen. The development of such a vaccine, which should trigger broad and strong B-cell and T-cell responses against antigens of the pathogen in question, is

Vaccine Adjuvant Incorporation Strategy Dictates Peptide Amphiphile Micelle Immunostimulatory Capacity.

Science.gov (United States)

Zhang, Rui; Kramer, Jake S; Smith, Josiah D; Allen, Brittany N; Leeper, Caitlin N; Li, Xiaolei; Morton, Logan D; Gallazzi, Fabio; Ulery, Bret D

2018-06-01

Current vaccine research has shifted from traditional vaccines (i.e., whole-killed or live-attenuated) to subunit vaccines (i.e., protein, peptide, or DNA) as the latter is much safer due to delivering only the bioactive components necessary to produce a desirable immune response. Unfortunately, subunit vaccines are very weak immunogens requiring delivery vehicles and the addition of immunostimulatory molecules termed adjuvants to convey protective immunity. An interesting type of delivery vehicle is peptide amphiphile micelles (PAMs), unique biomaterials where the vaccine is part of the nanomaterial itself. Due to the modularity of PAMs, they can be readily modified to deliver both vaccine antigens and adjuvants within a singular construct. Through the co-delivery of a model antigenic epitope (Ovalbumin 319-340 -OVA BT ) and a known molecular adjuvant (e.g., 2,3-dipalmitoyl-S-glyceryl cysteine-Pam 2 C), greater insight into the mechanisms by which PAMs can exert immunostimulatory effects was gained. It was found that specific combinations of antigen and adjuvant can significantly alter vaccine immunogenicity both in vitro and in vivo. These results inform fundamental design rules that can be leveraged to fabricate optimal PAM-based vaccine formulations for future disease-specific applications. Graphical Abstract.

Vaccine process technology.

Science.gov (United States)

Josefsberg, Jessica O; Buckland, Barry

2012-06-01

The evolution of vaccines (e.g., live attenuated, recombinant) and vaccine production methods (e.g., in ovo, cell culture) are intimately tied to each other. As vaccine technology has advanced, the methods to produce the vaccine have advanced and new vaccine opportunities have been created. These technologies will continue to evolve as we strive for safer and more immunogenic vaccines and as our understanding of biology improves. The evolution of vaccine process technology has occurred in parallel to the remarkable growth in the development of therapeutic proteins as products; therefore, recent vaccine innovations can leverage the progress made in the broader biotechnology industry. Numerous important legacy vaccines are still in use today despite their traditional manufacturing processes, with further development focusing on improving stability (e.g., novel excipients) and updating formulation (e.g., combination vaccines) and delivery methods (e.g., skin patches). Modern vaccine development is currently exploiting a wide array of novel technologies to create safer and more efficacious vaccines including: viral vectors produced in animal cells, virus-like particles produced in yeast or insect cells, polysaccharide conjugation to carrier proteins, DNA plasmids produced in E. coli, and therapeutic cancer vaccines created by in vitro activation of patient leukocytes. Purification advances (e.g., membrane adsorption, precipitation) are increasing efficiency, while innovative analytical methods (e.g., microsphere-based multiplex assays, RNA microarrays) are improving process understanding. Novel adjuvants such as monophosphoryl lipid A, which acts on antigen presenting cell toll-like receptors, are expanding the previously conservative list of widely accepted vaccine adjuvants. As in other areas of biotechnology, process characterization by sophisticated analysis is critical not only to improve yields, but also to determine the final product quality. From a regulatory

Novel thermal-sensitive hydrogel enhances both humoral and cell-mediated immune responses by intranasal vaccine delivery.

Science.gov (United States)

Wu, Youbin; Wu, Shipo; Hou, Lihua; Wei, Wei; Zhou, Meng; Su, Zhiguo; Wu, Jie; Chen, Wei; Ma, Guanghui

2012-08-01

A novel thermal sensitive hydrogel was formulated with N-[(2-hydroxy-3-trimethylammonium) propyl] chitosan chloride (HTCC) and α, β-glycerophosphate (α, β-GP). A serial of hydrogels containing different amount of GP and HTCC with diverse quarternize degree (QD, 41%, 59%, 79.5%, and 99%) were prepared and characterized by rheological method. The hydrogel was subsequently evaluated for intranasal vaccine delivery with adenovirus based Zaire Ebola virus glycoprotein antigen (Ad-GPZ). Results showed that moderate quarternized HTCC (60% and 79.5%) hydrogel/antigen formulations induced highest IgG, IgG1, and IgG2a antibody titers in serum, as well as mucosal IgA responses in lung wash, which may attributed to the prolonged antigen residence time due to the thermal-sensitivity of this hydrogel. Furthermore, CD8(+) splenocytes for IFN-γ positive cell assay and the release profile of Th1/Th2 type cytokines (IFN-γ, IL-2, IL-10, and IL-4) showed that hydrogel/Ad-GPZ generated an overwhelmingly enhanced Th1 biased cellular immune response. In addition, this hydrogel displayed low toxicity to nasal tissue and epithelial cells even by frequently intranasal dosing of hydrogel. All these results strongly supported this hydrogel as a safe and effective delivery system for nasal immunization. Crown Copyright © 2012. Published by Elsevier B.V. All rights reserved.

A Systems Approach to Nitrogen Delivery

Energy Technology Data Exchange (ETDEWEB)

Goins, Bobby [Y-12 National Security Complex, Oak Ridge, TN (United States)

2017-10-23

A systems based approach will be used to evaluate the nitrogen delivery process. This approach involves principles found in Lean, Reliability, Systems Thinking, and Requirements. This unique combination of principles and thought process yields a very in depth look into the system to which it is applied. By applying a systems based approach to the nitrogen delivery process there should be improvements in cycle time, efficiency, and a reduction in the required number of personnel needed to sustain the delivery process. This will in turn reduce the amount of demurrage charges that the site incurs. In addition there should be less frustration associated with the delivery process.

A Systems Approach to Nitrogen Delivery

Energy Technology Data Exchange (ETDEWEB)

Goins, Bobby [Y-12 National Security Complex, Oak Ridge, TN (United States); Univ. of Tennessee, Knoxville, TN (United States)

2017-10-17

A systems based approach will be used to evaluate the nitrogen delivery process. This approach involves principles found in Lean, Reliability, Systems Thinking, and Requirements. This unique combination of principles and thought process yields a very in depth look into the system to which it is applied. By applying a systems based approach to the nitrogen delivery process there should be improvements in cycle time, efficiency, and a reduction in the required number of personnel needed to sustain the delivery process. This will in turn reduce the amount of demurrage charges that the site incurs. In addition there should be less frustration associated with the delivery process.

Coated microneedle arrays for transcutaneous delivery of live virus vaccines

OpenAIRE

Vrdoljak, Anto; McGrath, Marie G.; Carey, John B.; Draper, Simon J.; Hill, Adrian V.S.; O’Mahony, Conor; Crean, Abina M.; Moore, Anne C.

2011-01-01

Vaccines are sensitive biologics that require continuous refrigerated storage to maintain their viability. The vast majority of vaccines are also administered using needles and syringes. The need for cold chain storage and the significant logistics surrounding needle-and-syringe vaccination is constraining the success of immunization programs. Recombinant live viral vectors are a promising platform for the development of vaccines against a number of infectious diseases, however these viruses ...

Alga-Produced Cholera Toxin-Pfs25 Fusion Proteins as Oral Vaccines

Science.gov (United States)

Gregory, James A.; Topol, Aaron B.; Doerner, David Z.

2013-01-01

Infectious diseases disproportionately affect indigent regions and are the greatest cause of childhood mortality in developing countries. Practical, low-cost vaccines for use in these countries are paramount to reducing disease burdens and concomitant poverty. Algae are a promising low-cost system for producing vaccines that can be orally delivered, thereby avoiding expensive purification and injectable delivery. We engineered the chloroplast of the eukaryotic alga Chlamydomonas reinhardtii to produce a chimeric protein consisting of the 25-kDa Plasmodium falciparum surface protein (Pfs25) fused to the β subunit of the cholera toxin (CtxB) to investigate an alga-based whole-cell oral vaccine. Pfs25 is a promising malaria transmission-blocking vaccine candidate that has been difficult to produce in traditional recombinant systems due to its structurally complex tandem repeats of epidermal growth factor-like domains. The noncatalytic CtxB domain of the cholera holotoxin assembles into a pentameric structure and acts as a mucosal adjuvant by binding GM1 ganglioside receptors on gut epithelial cells. We demonstrate that CtxB-Pfs25 accumulates as a soluble, properly folded and functional protein within algal chloroplasts, and it is stable in freeze-dried alga cells at ambient temperatures. In mice, oral vaccination using freeze-dried algae that produce CtxB-Pfs25 elicited CtxB-specific serum IgG antibodies and both CtxB- and Pfs25-specific secretory IgA antibodies. These data suggest that algae are a promising system for production and oral delivery of vaccine antigens, but as an orally delivered adjuvant, CtxB is best suited for eliciting secretory IgA antibodies for vaccine antigens against pathogens that invade mucosal surfaces using this strategy. PMID:23603678

Recombinant viruses as vaccines against viral diseases

Directory of Open Access Journals (Sweden)

A.P.D. Souza

2005-04-01

Full Text Available Vaccine approaches to infectious diseases are widely applied and appreciated. Amongst them, vectors based on recombinant viruses have shown great promise and play an important role in the development of new vaccines. Many viruses have been investigated for their ability to express proteins from foreign pathogens and induce specific immunological responses against these antigens in vivo. Generally, gene-based vaccines can stimulate potent humoral and cellular immune responses and viral vectors might be an effective strategy for both the delivery of antigen-encoding genes and the facilitation and enhancement of antigen presentation. In order to be utilized as a vaccine carrier, the ideal viral vector should be safe and enable efficient presentation of required pathogen-specific antigens to the immune system. It should also exhibit low intrinsic immunogenicity to allow for its re-administration in order to boost relevant specific immune responses. Furthermore, the vector system must meet criteria that enable its production on a large-scale basis. Several viral vaccine vectors have thus emerged to date, all of them having relative advantages and limits depending on the proposed application, and thus far none of them have proven to be ideal vaccine carriers. In this review we describe the potential, as well as some of the foreseeable obstacles associated with viral vaccine vectors and their use in preventive medicine.

Intradermal inactivated poliovirus vaccine: a preclinical dose-finding study.

Science.gov (United States)

Kouiavskaia, Diana; Mirochnitchenko, Olga; Dragunsky, Eugenia; Kochba, Efrat; Levin, Yotam; Troy, Stephanie; Chumakov, Konstantin

2015-05-01

Intradermal delivery of vaccines has been shown to result in dose sparing. We tested the ability of fractional doses of inactivated poliovirus vaccine (IPV) delivered intradermally to induce levels of serum poliovirus-neutralizing antibodies similar to immunization through the intramuscular route. Immunogenicity of fractional doses of IPV was studied by comparing intramuscular and intradermal immunization of Wistar rats using NanoPass MicronJet600 microneedles. Intradermal delivery of partial vaccine doses induced antibodies at titers comparable to those after immunization with full human dose delivered intramuscularly. The results suggest that intradermal delivery of IPV may lead to dose-sparing effect and reduction of the vaccination cost. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Archaeosomes: an excellent carrier for drug and cell delivery.

Science.gov (United States)

Kaur, Gurmeet; Garg, Tarun; Rath, Goutam; Goyal, Amit K

2016-09-01

Archaeosomes as liposomes made with one or more ether lipids that are unique to the domain of Archaeobacteria, found in Archaea constitute a novel family of liposome. Achaean-type lipids consist of archaeol (diether) and/or caldarchaeol (tetraether) core structures. Archaeosomes can be produced using standard procedures (hydrated film submitted to sonication, extrusion and detergent dialysis) at any temperature in the physiological range or lower, therefore making it possible to encapsulate thermally stable compounds. Various physiological as well as environmental factors affect its stability. Archaeosomes are widely used as drug delivery systems for cancer vaccines, Chagas disease, proteins and peptides, gene delivery, antigen delivery and delivery of natural antioxidant compounds. In this review article, our major aim was to explore the applications of this new carrier system in pharmaceutical field.

Current and future technological advances in transdermal gene delivery.

Science.gov (United States)

Chen, Xianfeng

2017-12-19

Transdermal gene delivery holds significant advantages as it is able to minimize the problems of systemic administration such as enzymatic degradation, systemic toxicity, and poor delivery to target tissues. This technology has the potential to transform the treatment and prevention of a range of diseases. However, the skin poses a great barrier for gene delivery because of the "bricks-and-mortar" structure of the stratum corneum and the tight junctions between keratinocytes in the epidermis. This review systematically summarizes the typical physical and chemical approaches to overcome these barriers and facilitate gene delivery via skin for applications in vaccination, wound healing, skin cancers and skin diseases. Next, the advantages and disadvantages of different approaches are discussed and the insights for future development are provided. Copyright © 2017 Elsevier B.V. All rights reserved.

Fiber coupled optical spark delivery system

Science.gov (United States)

Yalin, Azer; Willson, Bryan; Defoort, Morgan

2008-08-12

A spark delivery system for generating a spark using a laser beam is provided, the spark delivery system including a laser light source and a laser delivery assembly. The laser delivery assembly includes a hollow fiber and a launch assembly comprising launch focusing optics to input the laser beam in the hollow fiber. In addition, the laser delivery assembly includes exit focusing optics that demagnify an exit beam of laser light from the hollow fiber, thereby increasing the intensity of the laser beam and creating a spark. In accordance with embodiments of the present invention, the assembly may be used to create a spark in a combustion engine. In accordance with other embodiments of the present invention, a method of using the spark delivery system is provided. In addition, a method of choosing an appropriate fiber for creating a spark using a laser beam is also presented.

Sterile Product Packaging and Delivery Systems.

Science.gov (United States)

Akers, Michael J

2015-01-01

Both conventional and more advanced product container and delivery systems are the focus of this brief article. Six different product container systems will be discussed, plus advances in primary packaging for special delivery systems and needle technology.

Reduction of treatment delivery variances with a computer-controlled treatment delivery system

International Nuclear Information System (INIS)

Fraass, B.A.; Lash, K.L.; Matrone, G.M.; Lichter, A.S.

1997-01-01

Purpose: To analyze treatment delivery variances for 3-D conformal therapy performed at various levels of treatment delivery automation, ranging from manual field setup to virtually complete computer-controlled treatment delivery using a computer-controlled conformal radiotherapy system. Materials and Methods: All external beam treatments performed in our department during six months of 1996 were analyzed to study treatment delivery variances versus treatment complexity. Treatments for 505 patients (40,641 individual treatment ports) on four treatment machines were studied. All treatment variances noted by treatment therapists or quality assurance reviews (39 in all) were analyzed. Machines 'M1' (CLinac (6(100))) and 'M2' (CLinac 1800) were operated in a standard manual setup mode, with no record and verify system (R/V). Machines 'M3' (CLinac 2100CD/MLC) and ''M4'' (MM50 racetrack microtron system with MLC) treated patients under the control of a computer-controlled conformal radiotherapy system (CCRS) which 1) downloads the treatment delivery plan from the planning system, 2) performs some (or all) of the machine set-up and treatment delivery for each field, 3) monitors treatment delivery, 4) records all treatment parameters, and 5) notes exceptions to the electronically-prescribed plan. Complete external computer control is not available on M3, so it uses as many CCRS features as possible, while M4 operates completely under CCRS control and performs semi-automated and automated multi-segment intensity modulated treatments. Analysis of treatment complexity was based on numbers of fields, individual segments (ports), non-axial and non-coplanar plans, multi-segment intensity modulation, and pseudo-isocentric treatments (and other plans with computer-controlled table motions). Treatment delivery time was obtained from the computerized scheduling system (for manual treatments) or from CCRS system logs. Treatment therapists rotate among the machines, so this analysis

Nanoparticulate STING agonists are potent lymph node-targeted vaccine adjuvants.

Science.gov (United States)

Hanson, Melissa C; Crespo, Monica P; Abraham, Wuhbet; Moynihan, Kelly D; Szeto, Gregory L; Chen, Stephanie H; Melo, Mariane B; Mueller, Stefanie; Irvine, Darrell J

2015-06-01

Cyclic dinucleotides (CDNs) are agonists of stimulator of IFN genes (STING) and have potential as vaccine adjuvants. However, cyclic di-GMP (cdGMP) injected s.c. shows minimal uptake into lymphatics/draining lymph nodes (dLNs) and instead is rapidly distributed to the bloodstream, leading to systemic inflammation. Here, we encapsulated cdGMP within PEGylated lipid nanoparticles (NP-cdGMP) to redirect this adjuvant to dLNs. Compared with unformulated CDNs, encapsulation blocked systemic dissemination and markedly enhanced dLN accumulation in murine models. Delivery of NP-cdGMP increased CD8+ T cell responses primed by peptide vaccines and enhanced therapeutic antitumor immunity. A combination of a poorly immunogenic liposomal HIV gp41 peptide antigen and NP-cdGMP robustly induced type I IFN in dLNs, induced a greater expansion of vaccine-specific CD4+ T cells, and greatly increased germinal center B cell differentiation in dLNs compared with a combination of liposomal HIV gp41 and soluble CDN. Further, NP-cdGMP promoted durable antibody titers that were substantially higher than those promoted by the well-studied TLR agonist monophosphoryl lipid A and comparable to a much larger dose of unformulated cdGMP, without the systemic toxicity of the latter. These results demonstrate that nanoparticulate delivery safely targets CDNs to the dLNs and enhances the efficacy of this adjuvant. Moreover, this approach can be broadly applied to other small-molecule immunomodulators of interest for vaccines and immunotherapy.

CDC WONDER: Vaccine Adverse Event Reporting System (VAERS)

Data.gov (United States)

U.S. Department of Health & Human Services — The Vaccine Adverse Event Reporting System (VAERS) online database on CDC WONDER provides counts and percentages of adverse event case reports after vaccination, by...

MINI-SLAR delivery system

International Nuclear Information System (INIS)

Alstein, D.

1996-01-01

In the Spring of 1993, a need to complete Spacer Location and Repositioning (SLAR) on the Bruce 'A', Unit 1 Reactor was identified. An alternate SLAR delivery system was required due to conversion constraints that prevented the existing Bruce SLAR System from being used in Unit 1. A Portable SLAR Delivery System called MINI-SLAR Delivery System was developed, designed and fabricated in a 14 month period, then used to successfully SLAR 109 channels. The system is a portable remotely operated Nuclear Class 1 registered fitting that is independent of the Fuelling Machine, allowing the station to continue normal Fuelling and Maintenance activities. It is designed to a Level 'D' faulted condition of HPECI Pressure thus minimizing PHT Heat Sink configuration requirements and minimizing outage set-up times. The system is based on a modular design allowing for easy fabrication, assembly and repair. It consists of a Snout Assembly, a Closure Plug Assembly, Shield Plug Assembly, SLAR Ram assembly, Work Table Assembly and Control Panel. Controls are through a Programmable Logic Controller with software tested and certified to a Software Quality Assurance of Level Ill. (author). 2 refs., 2 figs

MINI-SLAR delivery system

Energy Technology Data Exchange (ETDEWEB)

Alstein, D [Ontario Hydro, Tiverton, ON (Canada). Bruce Nuclear Generating Station-A; Dalton, K [Spectrum Engineering, Peterborough, ON (Canada)

1997-12-31

In the Spring of 1993, a need to complete Spacer Location and Repositioning (SLAR) on the Bruce `A`, Unit 1 Reactor was identified. An alternate SLAR delivery system was required due to conversion constraints that prevented the existing Bruce SLAR System from being used in Unit 1. A Portable SLAR Delivery System called MINI-SLAR Delivery System was developed, designed and fabricated in a 14 month period, then used to successfully SLAR 109 channels. The system is a portable remotely operated Nuclear Class 1 registered fitting that is independent of the Fuelling Machine, allowing the station to continue normal Fuelling and Maintenance activities. It is designed to a Level `D` faulted condition of HPECI Pressure thus minimizing PHT Heat Sink configuration requirements and minimizing outage set-up times. The system is based on a modular design allowing for easy fabrication, assembly and repair. It consists of a Snout Assembly, a Closure Plug Assembly, Shield Plug Assembly, SLAR Ram assembly, Work Table Assembly and Control Panel. Controls are through a Programmable Logic Controller with software tested and certified to a Software Quality Assurance of Level Ill. (author). 2 refs., 2 figs.

Health care delivery systems.

NARCIS (Netherlands)

Stevens, F.; Zee, J. van der

2007-01-01

A health care delivery system is the organized response of a society to the health problems of its inhabitants. Societies choose from alternative health care delivery models and, in doing so, they organize and set goals and priorities in such a way that the actions of different actors are effective,

Designing and assessing a sustainable networked delivery (SND) system: hybrid business-to-consumer book delivery case study.

Science.gov (United States)

Kim, Junbeum; Xu, Ming; Kahhat, Ramzy; Allenby, Braden; Williams, Eric

2009-01-01

We attempted to design and assess an example of a sustainable networked delivery (SND) system: a hybrid business-to-consumer book delivery system. This system is intended to reduce costs, achieve significant reductions in energy consumption, and reduce environmental emissions of critical local pollutants and greenhouse gases. The energy consumption and concomitant emissions of this delivery system compared with existing alternative delivery systems were estimated. We found that regarding energy consumption, an emerging hybrid delivery system which is a sustainable networked delivery system (SND) would consume 47 and 7 times less than the traditional networked delivery system (TND) and e-commerce networked delivery system (END). Regarding concomitant emissions, in the case of CO2, the SND system produced 32 and 7 times fewer emissions than the TND and END systems. Also the SND system offer meaningful economic benefit such as the costs of delivery and packaging, to the online retailer, grocery, and consumer. Our research results show that the SND system has a lot of possibilities to save local transportation energy consumption and delivery costs, and reduce environmental emissions in delivery system.

Preventative vaccine-loaded mannosylated chitosan nanoparticles intended for nasal mucosal delivery enhance immune responses and potent tumor immunity.

Science.gov (United States)

Yao, Wenjun; Peng, Yixing; Du, Mingzhu; Luo, Juan; Zong, Li

2013-08-05

Chitosan (CS) has been extensively used as a protein drug and gene delivery carrier, but its delivery efficiency is unsatisfactory. In this study, a mannose ligand was used to modify CS, which could enhance the delivery efficiency of CS via mannose receptor-mediated endocytosis. A preventative anti-GRP DNA vaccine (pCR3.1-VS-HSP65-TP-GRP6-M2, pGRP) was condensed with mannosylated chitosan (MCS) to form MCS/pGRP nanoparticles. Nanoparticles were intranasally administered in a subcutaneous mice prostate carcinoma model to evaluate the efficacy on inhibition of the growth of tumor cells. The titers of anti-GRP IgG that lasted for 11 weeks were significantly higher than that for administration of CS/pGRP nanoparticles (p intramuscular administration of a pGRP solution (p nanoparticles could suppress the growth of tumor cells. The average tumor weight (0.79 ± 0.30 g) was significantly lower than that in the CS/pGRP nanoparticle group (1.69 ± 0.15 g) (p nanoparticles bound with C-type lectin receptors on macrophages. MCS was an efficient targeting gene delivery carrier and could be used in antitumor immunotherapy.

Porous silicon advances in drug delivery and immunotherapy.

Science.gov (United States)

Savage, David J; Liu, Xuewu; Curley, Steven A; Ferrari, Mauro; Serda, Rita E

2013-10-01

Biomedical applications of porous silicon include drug delivery, imaging, diagnostics and immunotherapy. This review summarizes new silicon particle fabrication techniques, dynamics of cellular transport, advances in the multistage vector approach to drug delivery, and the use of porous silicon as immune adjuvants. Recent findings support superior therapeutic efficacy of the multistage vector approach over single particle drug delivery systems in mouse models of ovarian and breast cancer. With respect to vaccine development, multivalent presentation of pathogen-associated molecular patterns on the particle surface creates powerful platforms for immunotherapy, with the porous matrix able to carry both antigens and immune modulators. Copyright © 2013 Elsevier Ltd. All rights reserved.

Biodegradable polymeric nanocarriers for pulmonary drug delivery.

Science.gov (United States)

Rytting, Erik; Nguyen, Juliane; Wang, Xiaoying; Kissel, Thomas

2008-06-01

Pulmonary drug delivery is attractive for both local and systemic drug delivery as a non-invasive route that provides a large surface area, thin epithelial barrier, high blood flow and the avoidance of first-pass metabolism. Nanoparticles can be designed to have several advantages for controlled and targeted drug delivery, including controlled deposition, sustained release, reduced dosing frequency, as well as an appropriate size for avoiding alveolar macrophage clearance or promoting transepithelial transport. This review focuses on the development and application of biodegradable polymers to nanocarrier-based strategies for the delivery of drugs, peptides, proteins, genes, siRNA and vaccines by the pulmonary route. The selection of natural or synthetic materials is important in designing particles or nanoparticle clusters with the desired characteristics, such as biocompatibility, size, charge, drug release and polymer degradation rate.

Proteliposome-derived Cochleate as an immunomodulator for nasal vaccine.

Science.gov (United States)

Pérez, Oliver; Bracho, Gustavo; Lastre, Miriam; Zayas, Caridad; González, Domingo; Gil, Danay; del Campo, Judith; Acevedo, Reinaldo; Taboada, Carlos; Rodríguez, Tamara; Fajardo, María E; Sierra, Gustavo; Campa, Concepción; Mora, Nestor; Barberá, Ramón; Solís, Rosa L

2006-04-12

Proteoliposome (PL) has been recently used as a protective intramuscular (i.m.) anti-meningococcal BC vaccine. It induces a preferential Th 1 type of immune response. Nevertheless, mucosal protection is mainly mediated by IgA antibody response, which is not usually induced by i.m. vaccination route. IgA antibody production needs the stimulation of Th3 subpopulation, which is also related to the induction of small dose tolerance. We hypothesized that PL-derived Cochleate can induce a specific mucosal IgA and systemic IgG antibody responses. We could show that mice immunized with two or three intranasal doses of PL-derived Cochleate developed significantly increased levels of local anti PL IgA and systemic IgG antibody responses. Thus, our results suggest that PL-derived Cochleate can be used as a promising immunomodulator and delivery system for the development of mucosal, particularly nasal vaccines.

Diagnosing avian influenza infection in vaccinated populations by systems for differentiating infected from vaccinated animals (DIVA).

Science.gov (United States)

Capua, I; Cattoli, G

2007-01-01

Vaccination against avian influenza is recommended as a tool to support control measures in countries affected by avian influenza. Vaccination is known to increase the resistance of susceptible birds to infection and also to reduce shedding; however, it does not always prevent infection. Vaccinated infected flocks can therefore be a source of infection and thus be responsible for the perpetuation of infection. To avoid the spread of infection in a vaccinated population, immunization strategies must allow differentiation of infected from vaccinated animals (DIVA), combined with an appropriate monitoring system. Vaccinated exposed flocks must be identified and managed by restriction policies that include controlled marketing and stamping-out. Several vaccines and diagnostic tests to detect infection in vaccinated populations are available, the tests having various properties and characteristics. In order to achieve eradication, the most appropriate DIVA vaccination strategy must be identified and an appropriate monitoring programme be designed, taking into account risk factors, the epidemiological situation and the socioeconomic implications of the policy.

mRNA Cancer Vaccines-Messages that Prevail.

Science.gov (United States)

Grunwitz, Christian; Kranz, Lena M

2017-01-01

During the last decade, mRNA became increasingly recognized as a versatile tool for the development of new innovative therapeutics. Especially for vaccine development, mRNA is of outstanding interest and numerous clinical trials have been initiated. Strikingly, all of these studies have proven that large-scale GMP production of mRNA is feasible and concordantly report a favorable safety profile of mRNA vaccines. Induction of T-cell immunity is a multi-faceted process comprising antigen acquisition, antigen processing and presentation, as well as immune stimulation. The effectiveness of mRNA vaccines is critically dependent on making the antigen(s) of interest available to professional antigen-presenting cells, especially DCs. Efficient delivery of mRNA into DCs in vivo remains a major challenge in the mRNA vaccine field. This review summarizes the principles of mRNA vaccines and highlights the importance of in vivo mRNA delivery and recent advances in harnessing their therapeutic potential.

Some Recent Advances in Transdermal Drug Delivery Systems ...

African Journals Online (AJOL)

Some Recent Advances in Transdermal Drug Delivery Systems. ... Advances in Transdermal Drug Delivery Systems. EC Ibezim, B Kabele-Toge, CO Anie, C Njoku. Abstract. Transdermal delivery systems are forms of drug delivery involving the dermis, as distinct from topical, oral or other forms of parenteral dosage forms.

Virosomes for antigen and DNA delivery

NARCIS (Netherlands)

Daemen, T; de Mare, A; Bungener, L; de Jonge, J; Huckriede, A; Wilschut, J

2005-01-01

Specific targeting and delivery as well as the display of antigens on the surface of professional antigen-presenting cells (APCs) are key issues in the design and development of new-generation vaccines aimed at the induction of both humoral and cell-mediated immunity. Prophylactic vaccination

Perspective on Global Measles Epidemiology and Control and the Role of Novel Vaccination Strategies

Directory of Open Access Journals (Sweden)

Melissa M. Coughlin

2017-01-01

Full Text Available Measles is a highly contagious, vaccine preventable disease. Measles results in a systemic illness which causes profound immunosuppression often leading to severe complications. In 2010, the World Health Assembly declared that measles can and should be eradicated. Measles has been eliminated in the Region of the Americas, and the remaining five regions of the World Health Organization (WHO have adopted measles elimination goals. Significant progress has been made through increased global coverage of first and second doses of measles-containing vaccine, leading to a decrease in global incidence of measles, and through improved case based surveillance supported by the WHO Global Measles and Rubella Laboratory Network. Improved vaccine delivery methods will likely play an important role in achieving measles elimination goals as these delivery methods circumvent many of the logistic issues associated with subcutaneous injection. This review highlights the status of global measles epidemiology, novel measles vaccination strategies, and describes the pathway toward measles elimination.

Oral Modeling of an Adenovirus-Based Quadrivalent Influenza Vaccine in Ferrets and Mice.

Science.gov (United States)

Scallan, Ciaran D; Lindbloom, Jonathan D; Tucker, Sean N

2016-06-01

Oral vaccines delivered as tablets offer a number of advantages over traditional parenteral-based vaccines including the ease of delivery, lack of needles, no need for trained medical personnel, and the ability to formulate into temperature-stable tablets. We have been evaluating an oral vaccine platform based on recombinant adenoviral vectors for the purpose of creating a prophylactic vaccine to prevent influenza, and have demonstrated vaccine efficacy in animal models and substantial immunogenicity in humans. These studies have evaluated monovalent vaccines to date. To protect against the major circulating A and B influenza strains, a multivalent influenza vaccine will be required. In this study, the immunogenicity of orally delivered monovalent, bivalent, trivalent, and quadrivalent vaccines was tested in ferrets and mice. The various vaccine combinations were tested by blending monovalent recombinant adenovirus vaccines, each expressing hemagglutinin from a single strain. Human tablet delivery was modeled in animals by oral gavage in mice and by endoscopic delivery in ferrets. We demonstrated minimal interference between the various vaccine vectors when used in combination and that the oral quadrivalent vaccine compared favorably to an approved trivalent inactivated vaccine. The quadrivalent vaccine presented here produced immune responses that we predict should be capable of providing protection against multiple influenza strains, and the platform should have applications to other multivalent vaccines. Vaxart, Inc.

Drug delivery systems with modified release for systemic and biophase bioavailability.

Science.gov (United States)

Leucuta, Sorin E

2012-11-01

This review describes the most important new generations of pharmaceutical systems: medicines with extended release, controlled release pharmaceutical systems, pharmaceutical systems for the targeted delivery of drug substances. The latest advances and approaches for delivering small molecular weight drugs and other biologically active agents such as proteins and nucleic acids require novel delivery technologies, the success of a drug being many times dependent on the delivery method. All these dosage forms are qualitatively superior to medicines with immediate release, in that they ensure optimal drug concentrations depending on specific demands of different disease particularities of the body. Drug delivery of these pharmaceutical formulations has the benefit of improving product efficacy and safety, as well as patient convenience and compliance. This paper describes the biopharmaceutical, pharmacokinetic, pharmacologic and technological principles in the design of drug delivery systems with modified release as well as the formulation criteria of prolonged and controlled release drug delivery systems. The paper presents pharmaceutical prolonged and controlled release dosage forms intended for different routes of administration: oral, ocular, transdermal, parenteral, pulmonary, mucoadhesive, but also orally fast dissolving tablets, gastroretentive drug delivery systems, colon-specific drug delivery systems, pulsatile drug delivery systems and carrier or ligand mediated transport for site specific or receptor drug targeting. Specific technologies are given on the dosage forms with modified release as well as examples of marketed products, and current research in these areas.

Health system challenges to integration of mental health delivery in primary care in Kenya- perspectives of primary care health workers

OpenAIRE

Jenkins, Rachel; Othieno, Caleb; Okeyo, Stephen; Aruwa, Julyan; Kingora, James; Jenkins, Ben

2013-01-01

Background Health system weaknesses in Africa are broadly well known, constraining progress on reducing the burden of both communicable and non-communicable disease (Afr Health Monitor, Special issue, 2011, 14-24), and the key challenges in leadership, governance, health workforce, medical products, vaccines and technologies, information, finance and service delivery have been well described (Int Arch Med, 2008, 1:27). This paper uses focus group methodology to explore health worker perspecti...

STUDY ON FEASIBILITY AND LOGISTICS OF VACCINATION WITH TYPHOID VI-VACCINE ON SCHOOL CHILDREN IN NORTH JAKARTA INDONESIA: ANALYSIS OF THE VACCINATION COST

Directory of Open Access Journals (Sweden)

Roy G.A. Massie

2012-11-01

Full Text Available Background: In recent years, Indonesia government has become increasingly concerned with the issues of financing childhood vaccines and immunization programs including vaccine for typhoid  fever. The objective of the analysis is to provide alternative resources and to provide understandable data generated from the Study on Feasibility and Logistics of Vaccination School Age Children With Typhoid Vi-Vaccine in North Jakarta Indonesia. Methods: The analysis was focus on measurement of the cost for vaccinating school children with Typhoid Vi-vaccine from 18 selected primary schools in North Jakarta. The primary source of data was generated from the actual expenditures that were used in the vaccine delivery program in Indonesia. Results: The Vaccination Cost from the Study on Feasibility and Logistics of Vaccination School Age Children with Typhoid Vi-Vaccine conducted by DOMI project is not applicable for public vaccination program. The program might be feasible to be delivered only in private health sector settings.   Key words: Immunization expenditure, vaccine for typhoid fever, North Jakarta Indonesia

New delivery systems for amphotericin B applied to the improvement of leishmaniasis treatment

Directory of Open Access Journals (Sweden)

Miguel Angel Chávez-Fumagalli

2015-06-01

Full Text Available Leishmaniasis is one of the six major tropical diseases targeted by the World Health Organization. It is a life-threatening disease of medical, social and economic importance in endemic areas. No vaccine is yet available for human use, and chemotherapy presents several problems. Pentavalent antimonials have been the drugs of choice to treat the disease for more than six decades; however, they exhibit high toxicity and are not indicated for children, for pregnant or breastfeeding women or for chronically ill patients. Amphotericin B (AmpB is a second-line drug, and although it has been increasingly used to treat visceral leishmaniasis (VL, its clinical use has been hampered due to its high toxicity. This review focuses on the development and in vivo usage of new delivery systems for AmpB that aim to decrease its toxicity without altering its therapeutic efficacy. These new formulations, when adjusted with regard to their production costs, may be considered new drug delivery systems that promise to improve the treatment of leishmaniasis, by reducing the side effects and the number of doses while permitting a satisfactory cost-benefit ratio.

Inflammation, Immunity, and Vaccines for Helicobacter pylori Infection

DEFF Research Database (Denmark)

Walduck, Anna; Andersen, Leif P; Raghavan, Sukanya

2015-01-01

studies that contribute with new insights in the host response to H. pylori infection. Also, the adaptive immune response to H. pylori and particularly the role of IL-22 have been addressed in some studies. These advances may improve vaccine development where new strategies have been published. Two major...... studies analyzed H. pylori genomes of 39 worldwide strains and looked at the protein profiles. In addition, multi-epitope vaccines for therapeutic use have been investigated. Studies on different adjuvants and delivery systems have also given us new insights. This review presents articles from the last...... year that reveal detailed insight into immunity and regulation of inflammation, the contribution of immune cells to the development of gastric cancer, and understanding mechanisms of vaccine-induced protection....

DNA fusion gene vaccines

DEFF Research Database (Denmark)

Holst, Peter Johannes; Bassi, Maria Rosaria; Thomsen, Allan Randrup

2010-01-01

DNA vaccines are versatile and safe, but limited immunogenicity has prevented their use in the clinical setting. Experimentally, immunogenicity may be enhanced by the use of new delivery technologies, by coadministration of cytokines and pathogen-associated molecular patterns, or by fusion...... of antigens into molecular domains that enhance antigen presentation. More specifically, the immunogenicity of DNA vaccines may benefit from increased protein synthesis, increased T-cell help and MHC class I presentation, and the addition of a range of specific cytokines and pathogen-associated molecular...... with viral-vectored vaccines, various synergistic components may need to be incorporated into DNA vaccines. From the perspective of the future clinical use of DNA vaccines, it has been suggested that antigen presentation should be improved and cytokine coadministration attempted. However, even...

Future of Automated Insulin Delivery Systems.

Science.gov (United States)

Castle, Jessica R; DeVries, J Hans; Kovatchev, Boris

2017-06-01

Advances in continuous glucose monitoring (CGM) have brought on a paradigm shift in the management of type 1 diabetes. These advances have enabled the automation of insulin delivery, where an algorithm determines the insulin delivery rate in response to the CGM values. There are multiple automated insulin delivery (AID) systems in development. A system that automates basal insulin delivery has already received Food and Drug Administration approval, and more systems are likely to follow. As the field of AID matures, future systems may incorporate additional hormones and/or multiple inputs, such as activity level. All AID systems are impacted by CGM accuracy and future CGM devices must be shown to be sufficiently accurate to be safely incorporated into AID. In this article, we summarize recent achievements in AID development, with a special emphasis on CGM sensor performance, and discuss the future of AID systems from the point of view of their input-output characteristics, form factor, and adaptability.

Vaccine strategies: Optimising outcomes.

Science.gov (United States)

Hardt, Karin; Bonanni, Paolo; King, Susan; Santos, Jose Ignacio; El-Hodhod, Mostafa; Zimet, Gregory D; Preiss, Scott

2016-12-20

Successful immunisation programmes generally result from high vaccine effectiveness and adequate uptake of vaccines. In the development of new vaccination strategies, the structure and strength of the local healthcare system is a key consideration. In high income countries, existing infrastructures are usually used, while in less developed countries, the capacity for introducing new vaccines may need to be strengthened, particularly for vaccines administered beyond early childhood, such as the measles or human papillomavirus (HPV) vaccine. Reliable immunisation service funding is another important factor and low income countries often need external supplementary sources of finance. Many regions also obtain support in generating an evidence base for vaccination via initiatives created by organisations including World Health Organization (WHO), the Pan American Health Organization (PAHO), the Agence de Médecine Préventive and the Sabin Vaccine Institute. Strong monitoring and surveillance mechanisms are also required. An example is the efficient and low-cost approaches for measuring the impact of the hepatitis B control initiative and evaluating achievement of goals that have been established in the WHO Western Pacific region. A review of implementation strategies reveals differing degrees of success. For example, in the Americas, PAHO advanced a measles-mumps-rubella vaccine strategy, targeting different population groups in mass, catch-up and follow-up vaccination campaigns. This has had much success but coverage data from some parts of the region suggest that children are still not receiving all appropriate vaccines, highlighting problems with local service infrastructures. Stark differences in coverage levels are also observed among high income countries, as is the case with HPV vaccine implementation in the USA versus the UK and Australia, reflecting differences in delivery settings. Experience and research have shown which vaccine strategies work well and the

Exploring pathways for building trust in vaccination and strengthening health system resilience

Directory of Open Access Journals (Sweden)

Sachiko Ozawa

2016-11-01

Full Text Available Abstract Background Trust is critical to generate and maintain demand for vaccines in low and middle income countries. However, there is little documentation on how health system insufficiencies affect trust in vaccination and the process of re-building trust once it has been compromised. We reflect on how disruptions to immunizations systems can affect trust in vaccination and can compromise vaccine utilization. We then explore key pathways for overcoming system vulnerabilities in order to restore trust, to strengthen the resilience of health systems and communities, and to promote vaccine utilization. Methods Utilizing secondary data and a review of the literature, we developed a causal loop diagram (CLD to map the determinants of building trust in immunizations. Using the CLD, we devised three scenarios to illustrate common vulnerabilities that compromise trust and pathways to strengthen trust and utilization of vaccines, specifically looking at weak health systems, harmful communication channels, and role of social capital. Spill-over effects, interactions and other dynamics in the CLD were then examined to assess leverage points to counter these vulnerabilities. Results Trust in vaccination arises from the interactions among experiences with the health system, the various forms of communication and social capital – both external and internal to communities. When experiencing system-wide shocks such as the case in Ebola-affected countries, distrust is reinforced by feedback between the health and immunization systems where distrust often lingers even after systems are restored and spills over beyond vaccination in the broader health system. Vaccine myths or anti-vaccine movements reinforce distrust. Social capital – the collective value of social networks of community members – plays a central role in increasing levels of trust. Conclusions Trust is important, yet underexplored, in the context of vaccine utilization. Using a CLD to

Costs of delivering human papillomavirus vaccination to schoolgirls in Mwanza Region, Tanzania

Science.gov (United States)

2012-01-01

Background Cervical cancer is the leading cause of female cancer-related deaths in Tanzania. Vaccination against human papillomavirus (HPV) offers a new opportunity to control this disease. This study aimed to estimate the costs of a school-based HPV vaccination project in three districts in Mwanza Region (NCT ID: NCT01173900), Tanzania and to model incremental scaled-up costs of a regional vaccination program. Methods We first conducted a top-down cost analysis of the vaccination project, comparing observed costs of age-based (girls born in 1998) and class-based (class 6) vaccine delivery in a total of 134 primary schools. Based on the observed project costs, we then modeled incremental costs of a scaled-up vaccination program for Mwanza Region from the perspective of the Tanzanian government, assuming that HPV vaccines would be delivered through the Expanded Programme on Immunization (EPI). Results Total economic project costs for delivering 3 doses of HPV vaccine to 4,211 girls were estimated at about US$349,400 (including a vaccine price of US$5 per dose). Costs per fully-immunized girl were lower for class-based delivery than for age-based delivery. Incremental economic scaled-up costs for class-based vaccination of 50,290 girls in Mwanza Region were estimated at US$1.3 million. Economic scaled-up costs per fully-immunized girl were US$26.41, including HPV vaccine at US$5 per dose. Excluding vaccine costs, vaccine could be delivered at an incremental economic cost of US$3.09 per dose and US$9.76 per fully-immunized girl. Financial scaled-up costs, excluding costs of the vaccine and salaries of existing staff were estimated at US$1.73 per dose. Conclusions Project costs of class-based vaccination were found to be below those of age-based vaccination because of more eligible girls being identified and higher vaccine uptake. We estimate that vaccine can be delivered at costs that would make HPV vaccination a very cost-effective intervention. Potentially

Aspects of Microparticle Utilization for Potentiation of Novel Vaccines: Promises and Risks

Science.gov (United States)

Ilyinskii, P.

Many recombinant vaccines against novel (HIV, HCV) or ever-changing (influenza) infectious agents require the presence of adjuvants/delivery vehicles to induce strong immune responses. The necessity of their improvement led to the major effort towards development of vaccine delivery systems that are generally particulate (e.g., nano- and microparticles) and have comparable dimensions to the pathogens (viruses or bacteria). The mode of action of these adjuvants is not fully understood but implies the stimulation of the innate or antigen-specific immune responses, and/or the increase of antigen uptake or processing by antigen-presenting cells (APC). Moreover, enhancement of adjuvant activity through the use of micro- and nanoparticulate delivery systems often resulted from the synergistic effects producing immune responses stronger than those elicited by the adjuvant or delivery system alone. Among particulate adjuvants, biodegradable micro- and nanoparticles of poly(D,L-lactide-co-glycoside) (PLGA) or poly(D,L-lactide) (PLA) have been reported to enhance both humoral and cellular immune responses against an encapsulated protein antigen. Cationic and anionic polylactide co-glycolide (PLG) microparticles have been successfully used to adsorb a variety of agents, which include plasmid DNA, recombinant proteins and adjuvant active oligonucleotides and are also currently tested in several vaccine applications. Another approach envisions specific targeting of APC, especially peripheral DC and exploitation of particulate systems that are small enough for lymphatic uptake (polystyrene nanobeads). Micro- and nanoparticles offer the possibility of enhancement of their uptake by appropriate cells through manipulation of their surface properties. Still, questions regarding toxicity and molecular interaction between micro- and nano-particles and immune cells, tissues and whole organisms remain to be addressed. These risks and other possible side effects should be assessed in

Development of a nasal adenovirus-based vaccine: Effect of concentration and formulation on adenovirus stability and infectious titer during actuation from two delivery devices.

Science.gov (United States)

Renteria, Sandra S; Clemens, Courtney C; Croyle, Maria A

2010-02-25

A nasal adenovirus-based vaccine is under development. To determine if aggregation occurs during vaccination, infectious titer (limiting dilution) and capsid integrity (dynamic light scattering) were assessed after extrusion of a model vector from two intranasal delivery devices. Preparations of 2.5x10(12) and 1.25x10(11) virus particles (vp)/ml were studied. Virus aggregated ( approximately 10%) in the multi-dose vessel. Virus titer dropped by one log. Virus in the unit-dose device aggregated ( approximately 1%). Titer remained unchanged. Aggregation was concentration dependent. Formulations prevented aggregation during actuation, freeze-thaw and long-term storage. The device, formulation and dose may significantly influence aggregation and potency of any nasal adenovirus 5-based vaccine. Copyright 2009 Elsevier Ltd. All rights reserved.

Liposome-Based Adjuvants for Subunit Vaccines: Formulation Strategies for Subunit Antigens and Immunostimulators

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Signe Tandrup Schmidt

2016-03-01

Full Text Available The development of subunit vaccines has become very attractive in recent years due to their superior safety profiles as compared to traditional vaccines based on live attenuated or whole inactivated pathogens, and there is an unmet medical need for improved vaccines and vaccines against pathogens for which no effective vaccines exist. The subunit vaccine technology exploits pathogen subunits as antigens, e.g., recombinant proteins or synthetic peptides, allowing for highly specific immune responses against the pathogens. However, such antigens are usually not sufficiently immunogenic to induce protective immunity, and they are often combined with adjuvants to ensure robust immune responses. Adjuvants are capable of enhancing and/or modulating immune responses by exposing antigens to antigen-presenting cells (APCs concomitantly with conferring immune activation signals. Few adjuvant systems have been licensed for use in human vaccines, and they mainly stimulate humoral immunity. Thus, there is an unmet demand for the development of safe and efficient adjuvant systems that can also stimulate cell-mediated immunity (CMI. Adjuvants constitute a heterogeneous group of compounds, which can broadly be classified into delivery systems or immunostimulators. Liposomes are versatile delivery systems for antigens, and they can carefully be customized towards desired immune profiles by combining them with immunostimulators and optimizing their composition, physicochemical properties and antigen-loading mode. Immunostimulators represent highly diverse classes of molecules, e.g., lipids, nucleic acids, proteins and peptides, and they are ligands for pattern-recognition receptors (PRRs, which are differentially expressed on APC subsets. Different formulation strategies might thus be required for incorporation of immunostimulators and antigens, respectively, into liposomes, and the choice of immunostimulator should ideally be based on knowledge regarding the

Skin immunization by microneedle patch overcomes statin-induced suppression of immune responses to influenza vaccine.

Science.gov (United States)

Vassilieva, Elena V; Wang, Shelly; Li, Song; Prausnitz, Mark R; Compans, Richard W

2017-12-19

Recent studies indicated that in elderly individuals, statin therapy is associated with a reduced response to influenza vaccination. The present study was designed to determine effects on the immune response to influenza vaccination induced by statin administration in a mouse model, and investigate potential approaches to improve the outcome of vaccination on the background of statin therapy. We fed middle aged BALB/c mice a high fat "western" diet (WD) alone or supplemented with atorvastatin (AT) for 14 weeks, and control mice were fed with the regular rodent diet. Mice were immunized with a single dose of subunit A/Brisbane/59/07 (H1N1) vaccine, either systemically or with dissolving microneedle patches (MNPs). We observed that a greater age-dependent decline in the hemagglutinin inhibition titers occurred in systemically-immunized mice than in MNP- immunized mice. AT dampened the antibody response in the animals vaccinated by either route of vaccine delivery. However, the MNP-vaccinated AT-treated animals had ~20 times higher total antibody levels to the influenza vaccine than the systemically vaccinated group one month postvaccination. We propose that microneedle vaccination against influenza provides an approach to ameliorate the immunosuppressive effect of statin therapy observed with systemic immunization.

Triple co-culture cell model as an in vitro model for oral particulate vaccine systems

DEFF Research Database (Denmark)

Nielsen, Line Hagner; De Rossi, C.; Lehr, C.-M.

the immunostimulatory ability of particulate vaccine formulations designed for oral delivery. Levels of cytokine production in response to vaccine administration were measured following particulate vaccine administration, as an indication of dendritic cell and macrophage activation. Precursors of cubosomes containing......; this was not observed with ovalbumin and blank solution. An example of the results is shown in Figure 2 for IL-17A. An established co-culture of Caco-2, THP-1 and MUTZ-3 cells showed promise as an in vitro model for testing of oral vaccine formulations. Mobility of co-culture immune cells as well as cytokine production...... with particle formulations. This was not the case when incubating with ovalbumin solution or blank. The ELISA screening assay showed production of a wide range of cytokines following culture incubation with cubosomes (with and without ovalbumin) and LPS solutions, indicative of a stimulatory effect...

Heterologous protein secretion in Lactococcus lactis: a novel antigen delivery system

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Langella P.

1999-01-01

Full Text Available Lactic acid bacteria (LAB are Gram-positive bacteria and are generally regarded as safe (GRAS organisms. Therefore, LAB could be used for heterologous protein secretion and they are good potential candidates as antigen delivery vehicles. To develop such live vaccines, a better control of protein secretion is required. We developed an efficient secretion system in the model LAB, Lactococcus lactis. Staphylococcal nuclease (Nuc was used as the reporter protein. We first observed that the quantity of secreted Nuc correlated with the copy number of the cloning vector. The nuc gene was cloned on a high-copy number cloning vector and no perturbation of the metabolism of the secreting strain was observed. Replacement of nuc native promoter by a strong lactococcal one led to a significant increase of nuc expression. Secretion efficiency (SE of Nuc in L. lactis was low, i.e., only 60% of the synthesized Nuc was secreted. Insertion of a synthetic propeptide between the signal peptide and the mature moiety of Nuc increased the SE of Nuc. On the basis of these results, we developed a secretion system and we applied it to the construction of an L. lactis strain which secretes a bovine coronavirus (BCV epitope-protein fusion (BCV-Nuc. BCV-Nuc was recognized by both anti-BCV and anti-Nuc antibodies. Secretion of this antigenic fusion is the first step towards the development of a novel antigen delivery system based on LAB-secreting strains.

Biocompatible anionic polymeric microspheres as priming delivery system for effetive HIV/AIDS Tat-based vaccines.

Directory of Open Access Journals (Sweden)

Fausto Titti

Full Text Available Here we describe a prime-boost regimen of vaccination in Macaca fascicularis that combines priming with novel anionic microspheres designed to deliver the biologically active HIV-1 Tat protein and boosting with Tat in Alum. This regimen of immunization modulated the IgG subclass profile and elicited a balanced Th1-Th2 type of humoral and cellular responses. Remarkably, following intravenous challenge with SHIV89.6Pcy243, vaccinees significantly blunted acute viremia, as compared to control monkeys, and this control was associated with significantly lower CD4+ T cell depletion rate during the acute phase of infection and higher ability to resume the CD4+ T cell counts in the post-acute and chronic phases of infection. The long lasting control of viremia was associated with the persistence of high titers anti-Tat antibodies whose profile clearly distinguished vaccinees in controllers and viremics. Controllers, as opposed to vaccinated and viremic cynos, exhibited significantly higher pre-challenge antibody responses to peptides spanning the glutamine-rich and the RGD-integrin-binding regions of Tat. Finally, among vaccinees, titers of anti-Tat IgG1, IgG3 and IgG4 subclasses had a significant association with control of viremia in the acute and post-acute phases of infection. Altogether these findings indicate that the Tat/H1D/Alum regimen of immunization holds promise for next generation vaccines with Tat protein or other proteins for which maintenance of the native conformation and activity are critical for optimal immunogenicity. Our results also provide novel information on the role of anti-Tat responses in the prevention of HIV pathogenesis and for the design of new vaccine candidates.

Crude childhood vaccination coverage in West Africa: Trends and predictors of completeness [version 1; referees: 1 approved, 3 approved with reservations

Directory of Open Access Journals (Sweden)

Jacob S. Kazungu

2017-02-01

Full Text Available Background: Africa has the lowest childhood vaccination coverage worldwide. If the full benefits of childhood vaccination programmes are to be enjoyed in sub-Saharan Africa, all countries need to improve on vaccine delivery to achieve and sustain high coverage. In this paper, we review trends in vaccination coverage, dropouts between vaccine doses and explored the country-specific predictors of complete vaccination in West Africa. Methods: We utilized datasets from the Demographic and Health Surveys Program, available for Benin, Burkina Faso, The Gambia, Ghana, Guinea, Cote d’Ivoire, Liberia, Mali, Niger, Nigeria, Senegal, Sierra Leone and Togo, to obtain coverage for Bacillus Calmette-Guerin, polio, measles, and diphtheria, pertussis and tetanus (DPT vaccines in children aged 12 – 23 months. We also calculated the DPT1-to-DPT3 and DPT1-to-measles dropouts, and proportions of the fully immunised child (FIC. Factors predictive of FIC were explored using Chi-squared tests and multivariable logistic regression. Results: Overall, there was a trend of increasing vaccination coverage. The proportion of FIC varied significantly by country (range 24.1-81.4%, mean 49%. DPT1-to-DPT3 dropout was high (range 5.1% -33.9%, mean 16.3%. Similarly, DPT1-measles dropout exceeded 10% in all but four countries. Although no single risk factor was consistently associated with FIC across these countries, maternal education, delivery in a health facility, possessing a vaccine card and a recent post delivery visit to a health facility were the key predictors of complete vaccination. Conclusions: The low numbers of fully immunised children and high dropout between vaccine doses highlights weaknesses and the need to strengthen the healthcare and routine immunization delivery systems in this region. Country-specific correlates of complete vaccination should be explored further to identify interventions required to increase vaccination coverage. Despite the promise

Communications data delivery system analysis task 2 report : high-level options for secure communications data delivery systems.

Science.gov (United States)

2012-05-16

This Communications Data Delivery System Analysis Task 2 report describes and analyzes options for Vehicle to Vehicle (V2V) and Vehicle to Infrastructure (V2I) communications data delivery systems using various communication media (Dedicated Short Ra...

Simulation model of converging-diverging (CD) nozzle to improve particle delivery system of deoxyribonucleic acid (DNA)

Science.gov (United States)

Sumarsono, Danardono A.; Ibrahim, Fera; Santoso, Satria P.; Sari, Gema P.

2018-02-01

Gene gun is a mechanical device which has been used to deliver DNA vaccine into the cells and tissues by increasing the uptake of DNA plasmid so it can generate a high immune response with less amount of DNA. Nozzle is an important part of the gene gun which used to accelerate DNA in particle form with a gas flow to reach adequate momentum to enter the epidermis of human skin and elicit immune response. We developed new designs of nozzle for gene gun to make DNA uptake more efficient in vaccination. We used Computational Fluid Dynamics (CFD) by Autodesk® Simulation 2015 to simulate static fluid pressure and velocity contour of supersonic wave and parametric distance to predict the accuracy of the new nozzle. The result showed that the nozzle could create a shockwave at the distance parametric to the object from 4 to 5 cm using fluid pressure varied between 0.8-1.2 MPa. This is indication a possibility that the DNA particle could penetrate under the mammalian skin. For the future research step, this new nozzle model could be considered for development the main component of the DNA delivery system in vaccination in vivo

Next generation vaccines.

Science.gov (United States)

Riedmann, Eva M

2011-07-01

In February this year, about 100 delegates gathered for three days in Vienna (Austria) for the Next Generation Vaccines conference. The meeting held in the Vienna Hilton Hotel from 23rd-25th February 2011 had a strong focus on biotech and industry. The conference organizer Jacob Fleming managed to put together a versatile program ranging from the future generation of vaccines to manufacturing, vaccine distribution and delivery, to regulatory and public health issues. Carefully selected top industry experts presented first-hand experience and shared solutions for overcoming the latest challenges in the field of vaccinology. The program also included several case study presentations on novel vaccine candidates in different stages of development. An interactive pre-conference workshop as well as interactive panel discussions during the meeting allowed all delegates to gain new knowledge and become involved in lively discussions on timely, interesting and sometimes controversial topics related to vaccines.

Preliminary evaluation of a thermosensitive chitosan hydrogel for Echinococcus granulosus vaccine delivery.

Science.gov (United States)

Umair, Saleh; Pernthaner, Anton; Deng, Qing; Gibson, Blake; Hook, Sarah; Heath, David

2017-03-15

The EG95 vaccine is effective in protecting grazing animals from infection with Echinococcus granulosus. Six male lambs were used in the study, two were each vaccinated subcutaneously with 50μg EG95/1mg Quil-A, two animals were each vaccinated with 50μg EG95/1mg Quil-A in 1% chitosan thermolabile gel subcutaneously, and two animals served as non-vaccinated controls. Two vaccinations were given at a 7 week interval. Two vaccinations induced a significantly higher antibody titre in the chitosan group compared with the Quil-A only group. The chitosan vaccine group also had a significantly higher antibody titre compared with a positive control sera from vaccinated and challenged sheep. Incorporating the EG95/Quil-A vaccine in a thermo-responsive chitosan sol-gel stimulated, after the second injection, a high level of antibody absorbance which remained high for at least one year. This response was significantly greater than the response to vaccine without the gel. Copyright © 2017 Elsevier B.V. All rights reserved.

Levodopa delivery systems: advancements in delivery of the gold standard.

Science.gov (United States)

Ngwuluka, Ndidi; Pillay, Viness; Du Toit, Lisa C; Ndesendo, Valence; Choonara, Yahya; Modi, Girish; Naidoo, Dinesh

2010-02-01

Despite the fact that Parkinson's disease (PD) was discovered almost 200 years ago, its treatment and management remain immense challenges because progressive loss of dopaminergic nigral neurons, motor complications experienced by the patients as the disease progresses and drawbacks of pharmacotherapeutic management still persist. Various therapeutic agents have been used in the management of PD, including levodopa (l-DOPA), selegiline, amantadine, bromocriptine, entacapone, pramipexole dihydrochloride and more recently istradefylline and rasagiline. Of all agents, l-DOPA although the oldest, remains the most effective. l-DOPA is easier to administer, better tolerated, less expensive and is required by almost all PD patients. However, l-DOPA's efficacy in advanced PD is significantly reduced due to metabolism, subsequent low bioavailability and irregular fluctuations in its plasma levels. Significant strides have been made to improve the delivery of l-DOPA in order to enhance its bioavailability and reduce plasma fluctuations as well as motor complications experienced by patients purportedly resulting from pulsatile stimulation of the striatal dopamine receptors. Drug delivery systems that have been instituted for the delivery of l-DOPA include immediate release formulations, liquid formulations, dispersible tablets, controlled release formulations, dual-release formulations, microspheres, infusion and transdermal delivery, among others. In this review, the l-DOPA-loaded drug delivery systems developed over the past three decades are elaborated. The ultimate aim was to assess critically the attempts made thus far directed at improving l-DOPA absorption, bioavailability and maintenance of constant plasma concentrations, including the drug delivery technologies implicated. This review highlights the fact that neuropharmaceutics is at a precipice, which is expected to spur investigators to take that leap to enable the generation of innovative delivery systems for the

Content of web-based continuing medical education about HPV vaccination.

Science.gov (United States)

Kornides, Melanie L; Garrell, Jacob M; Gilkey, Melissa B

2017-08-16

Addressing low HPV vaccination coverage will require U.S. health care providers to improve their recommendation practices and vaccine delivery systems. Because readily available continuing medical education (CME) could be an important tool for supporting providers in this process, we sought to assess the content of web-based CME activities related to HPV vaccination. We conducted a content analysis of web-based CME activities about HPV vaccination available to U.S. primary care providers in May-September 2016. Using search engines, educational clearinghouses, and our professional networks, we identified 15 activities eligible for study inclusion. Through a process of open coding, we identified 45 commonly occurring messages in the CME activities, which we organized into five topic areas: delivering recommendations for HPV vaccination, addressing common parent concerns, implementing office-based strategies to increase HPV vaccination coverage, HPV epidemiology, and guidelines for HPV vaccine administration and safety. Using a standardized abstraction form, two coders then independently assessed which of the 45 messages each CME activity included. CME activities varied in the amount of content they delivered, with inclusion of the 45 messages ranging from 17% to 86%. Across activities, the most commonly included messages were related to guidelines for HPV vaccine administration and safety. For example, all activities (100%) specified that routine administration is recommended for ages 11 and 12. Most activities (73%) also noted that provider recommendations are highly influential. Fewer activities modeled examples of effective recommendations (47%), gave specific approaches to addressing common parent concerns (47%), or included guidance on office-based strategies to increase coverage (40%). Given that many existing CME activities lack substantive content on how to change provider practice, future activities should focus on the practical application of interpersonal

Intradermal vaccination using the novel microneedle device MicronJet600: Past, present, and future.

Science.gov (United States)

Levin, Yotam; Kochba, Efrat; Hung, Ivan; Kenney, Richard

2015-01-01

Intradermal immunization has become a forefront of vaccine improvement, both scientifically and commercially. Newer technologies are being developed to address the need to reduce the dose required for vaccination and to improve the reliability and ease of injection, which have been major hurdles in expanding the number of approved vaccines using this route of administration. In this review, 7 y of clinical experience with a novel intradermal delivery device, the MicronJet600, which is a registered hollow microneedle that simplifies the delivery of liquid vaccines, are summarized. This device has demonstrated both significant dose-sparing and superior immunogenicity in various vaccine categories, as well as in diverse subject populations and age groups. These studies have shown that intradermal delivery using this device is safe, effective, and preferred by the subjects. Comparison with other intradermal devices and potential new applications for intradermal delivery that could be pursued in the future are also discussed.

A history of adolescent school based vaccination in Australia.

Science.gov (United States)

Ward, Kirsten; Quinn, Helen; Menzies, Robert; McIntyre, Peter

2013-06-30

As adolescents have become an increasingly prominent target group for vaccination, school-based vaccination has emerged as an efficient and effective method of delivering nationally recommended vaccines to this often hard to reach group. School-based delivery of vaccines has occurred in Australia for over 80 years and has demonstrated advantages over primary care delivery for this part of the population. In the last decade school-based vaccination programs have become routine practice across all Australian states and territories. Using existing records and the recollection of experts we have compiled a history of school-based vaccination in Australia, primarily focusing on adolescents. This work is copyright. Apart from any use as permitted under the Copyright Act 1968, no part may be reproduced by any process without prior written permission from the Commonwealth. Requests and inquiries concerning reproduction and rights should be addressed to the Commonwealth Copyright Administration, Attorney General's Department, Robert Garran Offices, National Circuit, Barton ACT 2600 or posted at http://www.ag.gov.au/cca.

Vaccines for Prevention of Cervical Cancer

International Nuclear Information System (INIS)

Mahomed, M.F.

2017-01-01

The characteristics of two prophylactic Human Papilloma Virus HPV vaccines and ethical issues related to HPV vaccination are reviewed in this paper. These vaccines have the potential of substantially reducing HPV-related morbidity and mortality, and in particular cervical cancer. The vaccines cannot treat women with current HPV infection or HPV related disease. They should be administered before the commencement of sexual activity. The ideal age group is adolescent girls between the ages 9-13. Both vaccines are highly efficacious and immunogenic and induce high levels of serum antibodies after three doses for all vaccine-related HPV types. School-based vaccination is considered as a costeffective method for its delivery. Adequate education of both clinicians and patients is an essential to ensure effective implementation when considering a national vaccination program. (author)

Effect of adjuvants on responses to skin immunization by microneedles coated with influenza subunit vaccine.

Directory of Open Access Journals (Sweden)

William C Weldon

Full Text Available Recent studies have demonstrated the effectiveness of vaccine delivery to the skin by vaccine-coated microneedles; however there is little information on the effects of adjuvants using this approach for vaccination. Here we investigate the use of TLR ligands as adjuvants with skin-based delivery of influenza subunit vaccine. BALB/c mice received 1 µg of monovalent H1N1 subunit vaccine alone or with 1 µg of imiquimod or poly(I:C individually or in combination via coated microneedle patches inserted into the skin. Poly(I:C adjuvanted subunit influenza vaccine induced similar antigen-specific immune responses compared to vaccine alone when delivered to the skin by microneedles. However, imiquimod-adjuvanted vaccine elicited higher levels of serum IgG2a antibodies and increased hemagglutination inhibition titers compared to vaccine alone, suggesting enhanced induction of functional antibodies. In addition, imiquimod-adjuvanted vaccine induced a robust IFN-γ cellular response. These responses correlated with improved protection compared to influenza subunit vaccine alone, as well as reduced viral replication and production of pro-inflammatory cytokines in the lungs. The finding that microneedle delivery of imiquimod with influenza subunit vaccine induces improved immune responses compared to vaccine alone supports the use of TLR7 ligands as adjuvants for skin-based influenza vaccines.

An Estimation of Private Household Costs to Receive Free Oral Cholera Vaccine in Odisha, India

Science.gov (United States)

Mogasale, Vittal; Kar, Shantanu K.; Kim, Jong-Hoon; Mogasale, Vijayalaxmi V.; Kerketta, Anna S.; Patnaik, Bikash; Rath, Shyam Bandhu; Puri, Mahesh K.; You, Young Ae; Khuntia, Hemant K.; Maskery, Brian; Wierzba, Thomas F.; Sah, Binod

2015-01-01

Background Service provider costs for vaccine delivery have been well documented; however, vaccine recipients’ costs have drawn less attention. This research explores the private household out-of-pocket and opportunity costs incurred to receive free oral cholera vaccine during a mass vaccination campaign in rural Odisha, India. Methods Following a government-driven oral cholera mass vaccination campaign targeting population over one year of age, a questionnaire-based cross-sectional survey was conducted to estimate private household costs among vaccine recipients. The questionnaire captured travel costs as well as time and wage loss for self and accompanying persons. The productivity loss was estimated using three methods: self-reported, government defined minimum daily wages and gross domestic product per capita in Odisha. Findings On average, families were located 282.7 (SD = 254.5) meters from the nearest vaccination booths. Most family members either walked or bicycled to the vaccination sites and spent on average 26.5 minutes on travel and 15.7 minutes on waiting. Depending upon the methodology, the estimated productivity loss due to potential foregone income ranged from $0.15 to $0.29 per dose of cholera vaccine received. The private household cost of receiving oral cholera vaccine constituted 24.6% to 38.0% of overall vaccine delivery costs. Interpretation The private household costs resulting from productivity loss for receiving a free oral cholera vaccine is a substantial proportion of overall vaccine delivery cost and may influence vaccine uptake. Policy makers and program managers need to recognize the importance of private costs and consider how to balance programmatic delivery costs with private household costs to receive vaccines. PMID:26352143

An Estimation of Private Household Costs to Receive Free Oral Cholera Vaccine in Odisha, India.

Directory of Open Access Journals (Sweden)

Vittal Mogasale

Full Text Available Service provider costs for vaccine delivery have been well documented; however, vaccine recipients' costs have drawn less attention. This research explores the private household out-of-pocket and opportunity costs incurred to receive free oral cholera vaccine during a mass vaccination campaign in rural Odisha, India.Following a government-driven oral cholera mass vaccination campaign targeting population over one year of age, a questionnaire-based cross-sectional survey was conducted to estimate private household costs among vaccine recipients. The questionnaire captured travel costs as well as time and wage loss for self and accompanying persons. The productivity loss was estimated using three methods: self-reported, government defined minimum daily wages and gross domestic product per capita in Odisha.On average, families were located 282.7 (SD = 254.5 meters from the nearest vaccination booths. Most family members either walked or bicycled to the vaccination sites and spent on average 26.5 minutes on travel and 15.7 minutes on waiting. Depending upon the methodology, the estimated productivity loss due to potential foregone income ranged from $0.15 to $0.29 per dose of cholera vaccine received. The private household cost of receiving oral cholera vaccine constituted 24.6% to 38.0% of overall vaccine delivery costs.The private household costs resulting from productivity loss for receiving a free oral cholera vaccine is a substantial proportion of overall vaccine delivery cost and may influence vaccine uptake. Policy makers and program managers need to recognize the importance of private costs and consider how to balance programmatic delivery costs with private household costs to receive vaccines.

Association of chitosan and aluminium as a new adjuvant strategy for improved vaccination.

Science.gov (United States)

Lebre, F; Bento, D; Ribeiro, J; Colaço, M; Borchard, G; de Lima, M C Pedroso; Borges, O

2017-07-15

The use of particulate adjuvants offers an interesting possibility to enhance and modulate the immune responses elicited by vaccines. Aluminium salts have been extensively used as vaccine adjuvants, but they lack the capacity to induce a strong cellular and mucosal immune response. Taking this into consideration, in this study we designed a new antigen delivery system combining aluminium salts with chitosan. Chitosan-aluminium nanoparticles (CH-Al NPs) exhibited a mean diameter of 280nm and a positive surface charge. The newly developed CH-Al NPs are more stable at physiological environment than classical CH NPs, showing no cytotoxic effects and revealing potential as a delivery system for a wide range of model antigens. In vivo studies showed that mice immunized with hepatitis B surface antigen (HBsAg)-containing CH NPs display high anti-HBsAg IgG titers in the serum, as well as the highest antigen-specific IgG on vaginal washes. Furthermore, in contrast to mice receiving antigen alone, mice immunized with the particulate adjuvant were able to elicit IgG2c antibody titers and exhibited higher antigen-specific IFN-γ levels in splenocytes. In conclusion, we established that CH-Al NPs, combining two immunostimulants to enhance both humoral and cellular immune responses, are a safe and promising system for antigen delivery. Our findings point towards their potential in future vaccination approaches. Copyright © 2017 Elsevier B.V. All rights reserved.

Intradermal Inactivated Poliovirus Vaccine: A Preclinical Dose-Finding Study

OpenAIRE

Kouiavskaia, Diana; Mirochnitchenko, Olga; Dragunsky, Eugenia; Kochba, Efrat; Levin, Yotam; Troy, Stephanie; Chumakov, Konstantin

2014-01-01

Intradermal delivery of vaccines has been shown to result in dose sparing. We tested the ability of fractional doses of inactivated poliovirus vaccine (IPV) delivered intradermally to induce levels of serum poliovirus-neutralizing antibodies similar to immunization through the intramuscular route. Immunogenicity of fractional doses of IPV was studied by comparing intramuscular and intradermal immunization of Wistar rats using NanoPass MicronJet600 microneedles. Intradermal delivery of partial...

Green revolution vaccines, edible vaccines

African Journals Online (AJOL)

Admin

of development. Food vaccines may also help to suppress autoimmunity disorders such as Type-1. Diabetes. Key words: Edible vaccines, oral vaccines, antigen expression, food vaccines. INTRODUCTION. Vaccination involves the stimulation of the immune system to prepare it for the event of an invasion from a particular ...

One size does not fit all: The impact of primary vaccine container size on vaccine distribution and delivery.

Science.gov (United States)

Haidari, Leila A; Wahl, Brian; Brown, Shawn T; Privor-Dumm, Lois; Wallman-Stokes, Cecily; Gorham, Katie; Connor, Diana L; Wateska, Angela R; Schreiber, Benjamin; Dicko, Hamadou; Jaillard, Philippe; Avella, Melanie; Lee, Bruce Y

2015-06-22

While the size and type of a vaccine container (i.e., primary container) can have many implications on the safety and convenience of a vaccination session, another important but potentially overlooked consideration is how the design of the primary container may affect the distribution of the vaccine, its resulting cost, and whether the vial is ultimately opened. Using our HERMES software platform, we developed a simulation model of the World Health Organization Expanded Program on Immunization supply chain for the Republic of Benin and used the model to explore the effects of different primary containers for various vaccine antigens. Replacing vaccines with presentations containing fewer doses per vial reduced vaccine availability (proportion of people arriving for vaccines who are successfully immunized) by as much as 13% (from 73% at baseline) and raised logistics costs by up to $0.06 per dose administered (from $0.25 at baseline) due to increased bottlenecks, while reducing total costs by as much as $0.15 per dose administered (from $2.52 at baseline) due to lower open vial wastage. Primary containers with a greater number of doses per vial each improved vaccine availability by 19% and reduced logistics costs by $0.05 per dose administered, while reducing the total costs by up to $0.25 per dose administered. Changes in supply chain performance were more extreme in departments with greater constraints. Implementing a vial opening threshold reversed the direction of many of these effects. Our results show that one size may not fit all when choosing a primary vaccine container. Rather, the choice depends on characteristics of the vaccine, the vaccine supply chain, immunization session size, and goals of decision makers. In fact, the optimal vial size may vary among locations within a country. Simulation modeling can help identify tailored approaches to improve availability and efficiency. Copyright © 2015 Elsevier Ltd. All rights reserved.

Safety of currently licensed hepatitis B surface antigen vaccines in the United States, Vaccine Adverse Event Reporting System (VAERS), 2005-2015.

Science.gov (United States)

Haber, Penina; Moro, Pedro L; Ng, Carmen; Lewis, Paige W; Hibbs, Beth; Schillie, Sarah F; Nelson, Noele P; Li, Rongxia; Stewart, Brock; Cano, Maria V

2018-01-25

Currently four recombinant hepatitis B (HepB) vaccines are in use in the United States. HepB vaccines are recommended for infants, children and adults. We assessed adverse events (AEs) following HepB vaccines reported to the Vaccine Adverse Event Reporting System (VAERS), a national spontaneous reporting system. We searched VAERS for reports of AEs following single antigen HepB vaccine and HepB-containing vaccines (either given alone or with other vaccines), from January 2005 - December 2015. We conducted descriptive analyses and performed empirical Bayesian data mining to assess disproportionate reporting. We reviewed serious reports including reports of special interest. VAERS received 20,231 reports following HepB or HepB-containing vaccines: 10,291 (51%) in persons 18 years; for 1485 (7.3%) age was missing. Dizziness and nausea (8.4% each) were the most frequently reported AEs following a single antigen HepB vaccine: fever (23%) and injection site erythema (11%) were most frequent following Hep-containing vaccines. Of the 4444 (22%) reports after single antigen HepB vaccine, 303 (6.8%) were serious, including 45 deaths. Most commonly reported cause of death was Sudden Infant Death Syndrome (197). Most common non-death serious reports following single antigen HepB vaccines among infants aged children aged 1-23 months; infections and infestation (8) among persons age 2-18 years blood and lymphatic systemic disorders; and general disorders and administration site conditions among persons age >18 years. Most common vaccination error following single antigen HepB was incorrect product storage. Review current U.S.-licensed HepB vaccines administered alone or in combination with other vaccines did not reveal new or unexpected safety concerns. Vaccination errors were identified which indicate the need for training and education of providers on HepB vaccine indications and recommendations. Published by Elsevier Ltd.

Human papillomavirus vaccine policy and delivery in Latin America and the Caribbean.

Science.gov (United States)

Andrus, Jon Kim; Lewis, Merle J; Goldie, Sue J; García, Patricia J; Winkler, Jennifer L; Ruiz-Matus, Cuauhtémoc; de Quadros, Ciro A

2008-08-19

Cervical cancer caused by human papillomavirus (HPV) is a major preventable public health problem. Two vaccines are now available for primary prevention of HPV infection and their introduction offers new opportunities to enhance comprehensive cervical cancer prevention and control. Currently, HPV vaccine price is a significant barrier to rapid vaccine introduction and access. Therefore, making evidence-based decisions about whether and how to introduce HPV vaccine into the immunization schedule in the countries of Latin America and the Caribbean (LAC) requires a rigorous analysis of several factors. These include: estimates of disease burden, cost-effectiveness, operational feasibility of reaching a population of adolescent females and other key analyses that have been used in recent years to support the introduction of other vaccines, such as rotavirus and pneumococcal conjugate vaccines. Given the large number of public health priorities that are competing for limited public resources, developing and using a sound evidence base is of particular importance for vaccines, like HPV, which are currently available only at prices higher than other vaccines now in use. HPV vaccination provides the opportunity to dramatically improve women's health and partnerships must also be broad-based and effectively coordinated. This can be achieved by developing programs based on the lessons learned from vaccination strategies used to eliminate rubella and neonatal tetanus and for scaling up influenza vaccination in countries of LAC.

Ion-Responsive Drug Delivery Systems.

Science.gov (United States)

Yoshida, Takayuki; Shakushiro, Kohsuke; Sako, Kazuhiro

2018-02-08

Some kinds of cations and anions are contained in body fluids such as blood, interstitial fluid, gastrointestinal juice, and tears at relatively high concentration. Ionresponsive drug delivery is available to design the unique dosage formulations which provide optimized drug therapy with effective, safe and convenient dosing of drugs. The objective of the present review was to collect, summarize, and categorize recent research findings on ion-responsive drug delivery systems. Ions in body fluid/formulations caused structural changes of polymers/molecules contained in the formulations, allow formulations exhibit functions. The polymers/molecules responding to ions were ion-exchange resins/fibers, anionic or cationic polymers, polymers exhibiting transition at lower critical solution temperature, self-assemble supramolecular systems, peptides, and metalorganic frameworks. The functions of ion-responsive drug delivery systems were categorized to controlled drug release, site-specific drug release, in situ gelation, prolonged retention at the target sites, and enhancement of drug permeation. Administration of the formulations via oral, ophthalmic, transdermal, and nasal routes has showed significant advantages in the recent literatures. Many kinds of drug delivery systems responding to ions have been reported recently for several administration routes. Improvement and advancement of these systems can maximize drugs potential and contribute to patients in the world. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Evaluation of oral and subcutaneous delivery of an experimental canarypox recombinant canine distemper vaccine in the Siberian polecate (Mustela eversmanni)

Science.gov (United States)

Wimsatt, Jeffrey; Biggins, Dean E.; Innes, Kim; Taylor, Bobbi; Garell, Della

2003-01-01

the treatment groups. Survival rates were higher in animals with increasing serum neutralization titers (P = 0.027). This study demonstrates the efficacy of oral delivery of a recombinant CDV vaccine in the Siberian polecat. Further studies are needed to evaluate the safety and efficacy of vectored recombinant vaccines in highly susceptible species and especially in those species in which vaccination with modified live CDV has led to disease.

Recombinant expression systems: the obstacle to helminth vaccines?

Science.gov (United States)

Geldhof, Peter; De Maere, Veerle; Vercruysse, Jozef; Claerebout, Edwin

2007-11-01

The need for alternative ways to control helminth parasites has in recent years led to a boost in vaccination experiments with recombinant antigens. Despite the use of different expression systems, only a few recombinants induced high levels of protection against helminths. This is often attributed to the limitations of the current expression systems. Therefore, the need for new systems that can modify and glycosylate the expressed antigens has been advocated. However, analysis of over 100 published vaccine trials with recombinant helminth antigens indicates that it is often not known whether the native parasite antigen itself can induce protection or, if it does, which epitopes are important. This information is vital for a well-thought-out strategy for recombinant production. So, in addition to testing more expression systems, it should be considered that prior evaluation and characterization of the native antigens might help the development of recombinant vaccines against helminths in the long term.

Controlling chitosan-based encapsulation for protein and vaccine delivery

Science.gov (United States)

Koppolu, Bhanu prasanth; Smith, Sean G.; Ravindranathan, Sruthi; Jayanthi, Srinivas; Kumar, Thallapuranam K.S.; Zaharoff, David A.

2014-01-01

Chitosan-based nano/microencapsulation is under increasing investigation for the delivery of drugs, biologics and vaccines. Despite widespread interest, the literature lacks a defined methodology to control chitosan particle size and drug/protein release kinetics. In this study, the effects of precipitation-coacervation formulation parameters on chitosan particle size, protein encapsulation efficiency and protein release were investigated. Chitosan particle sizes, which ranged from 300 nm to 3 μm, were influenced by chitosan concentration, chitosan molecular weight and addition rate of precipitant salt. The composition of precipitant salt played a significant role in particle formation with upper Hofmeister series salts containing strongly hydrated anions yielding particles with a low polydispersity index (PDI) while weaker anions resulted in aggregated particles with high PDIs. Sonication power had minimal effect on mean particle size, however, it significantly reduced polydispersity. Protein loading efficiencies in chitosan nano/microparticles, which ranged from 14.3% to 99.2%, was inversely related to the hydration strength of precipitant salts, protein molecular weight and directly related to the concentration and molecular weight of chitosan. Protein release rates increased with particle size and were generally inversely related to protein molecular weight. This study demonstrates that chitosan nano/microparticles with high protein loading efficiencies can be engineered with well-defined sizes and controllable release kinetics through manipulation of specific formulation parameters. PMID:24560459

A Comprehensive Review on: Transdermal drug delivery systems.

OpenAIRE

Kharat, Rekha; Bathe, Ritesh Suresh

2016-01-01

Transdermal drug delivery system was introduced to overcome the difficulties of drug delivery through oral route. Despite their relatively higher costs, transdermal delivery systems have proved advantageous for delivery of selected drugs, such as estrogens, testosterone, clonidine and nitro-glycerine. Transdermal delivery provides a leading edge over injectable and oral routes by increasing patient compliance and avoiding first pass metabolism respectively. Topical  administration  of  therap...

Strategies to advance vaccine technologies for resource-poor settings.

Science.gov (United States)

Kristensen, Debra; Chen, Dexiang

2013-04-18

New vaccine platform and delivery technologies that can have significant positive impacts on the effectiveness, acceptability, and safety of immunizations in developing countries are increasingly available. Although donor support for vaccine technology development is strong, the uptake of proven technologies by the vaccine industry and demand for them by purchasers continues to lag. This article explains the challenges and opportunities associated with accelerating the availability of innovative and beneficial vaccine technologies to meet critical needs in resource-poor settings over the next decade. Progress will require increased dialog between the public and private sectors around vaccine product attributes; establishment of specifications for vaccines that mirror programmatic needs; stronger encouragement of vaccine developers to consider novel technologies early in the product development process; broader facilitation of research and access to technologies through the formation of centers of excellence; the basing of vaccine purchase decisions on immunization systems costs rather than price per dose alone; possible subsidization of early technology adoption costs for vaccine producers that take on the risks of new technologies of importance to the public sector; and the provision of data to purchasers, better enabling them to make informed decisions that take into account the value of specific product attributes. Copyright © 2012 Elsevier Ltd. All rights reserved.

Electronic Nicotine Delivery Systems Key Facts Infographic

Data.gov (United States)

U.S. Department of Health & Human Services — Explore the Electronic Nicotine Delivery Systems Key Facts Infographic which outlines key facts related to electronic nicotine delivery systems (ENDS), including...

Cost Evaluation of a Government-Conducted Oral Cholera Vaccination Campaign-Haiti, 2013.

Science.gov (United States)

Routh, Janell A; Sreenivasan, Nandini; Adhikari, Bishwa B; Andrecy, Lesly L; Bernateau, Margarette; Abimbola, Taiwo; Njau, Joseph; Jackson, Ernsley; Juin, Stanley; Francois, Jeannot; Tohme, Rania A; Meltzer, Martin I; Katz, Mark A; Mintz, Eric D

2017-10-01

The devastating 2010 cholera epidemic in Haiti prompted the government to introduce oral cholera vaccine (OCV) in two high-risk areas of Haiti. We evaluated the direct costs associated with the government's first vaccine campaign implemented in August-September 2013. We analyzed data for major cost categories and assessed the efficiency of available campaign resources to vaccinate the target population. For a target population of 107,906 persons, campaign costs totaled $624,000 and 215,295 OCV doses were dispensed. The total vaccine and operational cost was $2.90 per dose; vaccine alone cost $1.85 per dose, vaccine delivery and administration $0.70 per dose, and vaccine storage and transport $0.35 per dose. Resources were greater than needed-our analyses suggested that approximately 2.5-6 times as many persons could have been vaccinated during this campaign without increasing the resources allocated for vaccine delivery and administration. These results can inform future OCV campaigns in Haiti.

A New Decade of Vaccines

LENUS (Irish Health Repository)

Murphy, JFA

2011-09-01

The call for a new decade of vaccines was made in December 2010. The aims are to secure the further discovery, development and delivery of vaccination. The first challenge is the acquisition of funds for the research and development of 20 new vaccines1. The Gates Foundation has pledged $10 billion for this venture. The other major players are WHO, UNICEF and the US National Institute of Allergy and Infectious Diseases. The top priorities are TB, AIDS and Malaria. It is hoped that a Malaria vaccine will available in 3 years. The ambitious target of saving the lives of over 7 million children has been set. The programme must also address the need for vaccines in insulin dependent diabetes, cancers and degenerative diseases2.

The mental models of vaccination, trust in health care system and parental attitudes towards childhood vaccination

Directory of Open Access Journals (Sweden)

Bojan Gjorgjievski

2016-11-01

Full Text Available Many contradictory notions have been appearing in the area of health care in recent years, including those related to attitudes towards vaccination. On the basis of their understanding of the phenomenon some parents oppose to the vaccination. The purpose of this study was to compare mental models of laymen with expert models and examine the correlation of the mental models of vaccination and the trust in doctors and healthcare system with the parental attitudes on childhood vaccination. In doing so, we have considered the demographic characteristics of the parents and cultural differences between parents from Slovenia and Macedonia. We were also interested in the role of compulsory and optional vaccination, because in the latter the behavioral intention is expressed more clearly. The methods used in our study of mental models was based on the approach of Morgan, Fischhoff, Bostrom and Atman (2002 which has three phases: (1 obtaining expert mental models, (2 getting mental models of the laymen (e.g., parents and (3 comparison of both mental models. Expert models of vaccination were obtained from five doctors from Slovenia and five doctors from Macedonia. Laymen models of vaccination were obtained in structured interviews with 33 parents from Slovenia and 30 from Macedonia. Based on comparisons of expert and laymental models it can be concluded that the mental models of vaccination from parents of one-year old children differ from expert mental models. Most parents, both Macedonian and Slovenian, have also responded that they have greater confidence in the doctors rather than the healthcare system, mainly due to positive experiences with the selected pediatrician. In some Slovenian parents, a tendency to identify compulsory vaccination with force was noticed.

Complementing nuclear techniques with DNA vaccine technologies for improving animal health

International Nuclear Information System (INIS)

Relucio, J.L.V.; Dacanay, M.E.K.; Maligalig, A.C.S.; Ramos, E.A.; Santos, A.D.; Torres-Villanueva, C.A.T.; Osorio, R.G.; Deocaris, C.C.

2005-01-01

The use of nuclear methods can enhance several features of DNA vaccines in protecting livestock against pathogens. While DNA vaccines already have several advantages over their traditional predecessors (e.g. cheap production, stability over a wide range of temperature, amenability to genetic manipulation, and no risk of reversion to pathogenicity), conventional gene delivery systems make immunization of livestock and aquaculture populations tedious. For this reason, we are developing radiation-synthesized intelligent delivery systems for DNA vaccines. We encapsulated a reporter construct pCMV·SPORT-β-gal in radiation-synthesized κ-carrageenan-polyvinylpyrrolidone microspheres IP20 (for stomach release) and IP18 (for intestinal release). The DNA-loaded polymers were orally administered to Oreochromis niloticus (black Nile tilapia), and whole organs were stained with X-gal to observe β-galactosidase activity. Intense staining was observed in the stomach regions with IP20, while minimal staining was observed with IP18. The gills, in contrast, did not express β-galactosidase activity. Our results show evidence of the successful gene delivery capabilities of radiation-synthesized microspheres. When monitoring the progress of an animal's immune response after DNA immunization, non-invasive and sensitive methods are preferred. We also evaluated chicken egg-yolk polyclonal antibody response (chIgY) after direct intramuscular inoculation of the Hepatitis B Surface antigen expression vector pRc/CMV-HBs(S). Radioimmunoassay (RIA) was done to maximize sensitivity for determining antibody levels. Polyclonal antibody titres were observed to have increased after six weeks. Results of the RIA using the chIgY were comparable to that of immunized sera. Our findings indicate that chIgY could offer a cheaper and more animal-friendly antibody source and could be derived with the advantage of epitope specificity through DNA vaccination. (author)

Smart Drug Delivery Systems in Cancer Therapy.

Science.gov (United States)

Unsoy, Gozde; Gunduz, Ufuk

2018-02-08

Smart nanocarriers have been designed for tissue-specific targeted drug delivery, sustained or triggered drug release and co-delivery of synergistic drug combinations to develop safer and more efficient therapeutics. Advances in drug delivery systems provide reduced side effects, longer circulation half-life and improved pharmacokinetics. Smart drug delivery systems have been achieved successfully in the case of cancer. These nanocarriers can serve as an intelligent system by considering the differences of tumor microenvironment from healthy tissue, such as low pH, low oxygen level, or high enzymatic activity of matrix metalloproteinases. The performance of anti-cancer agents used in cancer diagnosis and therapy is improved by enhanced cellular internalization of smart nanocarriers and controlled drug release. Here, we review targeting, cellular internalization; controlled drug release and toxicity of smart drug delivery systems. We are also emphasizing the stimulus responsive controlled drug release from smart nanocarriers. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Lactococcus lactis carrying a DNA vaccine coding for the ESAT-6 antigen increases IL-17 cytokine secretion and boosts the BCG vaccine immune response.

Science.gov (United States)

Pereira, V B; da Cunha, V P; Preisser, T M; Souza, B M; Turk, M Z; De Castro, C P; Azevedo, M S P; Miyoshi, A

2017-06-01

A regimen utilizing Bacille Calmette-Guerin (BCG) and another vaccine system as a booster may represent a promising strategy for the development of an efficient tuberculosis vaccine for adults. In a previous work, we confirmed the ability of Lactococcus lactis fibronectin-binding protein A (FnBPA+) (pValac:ESAT-6), a live mucosal DNA vaccine, to produce a specific immune response in mice after oral immunization. In this study, we examined the immunogenicity of this strain as a booster for the BCG vaccine in mice. After immunization, cytokine and immunoglobulin profiles were measured. The BCG prime L. lactis FnBPA+ (pValac:ESAT-6) boost group was the most responsive group, with a significant increase in splenic pro-inflammatory cytokines IL-17, IFN-γ, IL-6 and TNF-α compared with the negative control. Based on the results obtained here, we demonstrated that L. lactis FnBPA+ (pValac:ESAT-6) was able to increase the BCG vaccine general immune response. This work is of great scientific and social importance because it represents the first step towards the development of a booster to the BCG vaccine using L. lactis as a DNA delivery system. © 2017 The Society for Applied Microbiology.

A phase 1, open-label, randomized study to compare the immunogenicity and safety of different administration routes and doses of virosomal influenza vaccine in elderly.

Science.gov (United States)

Levin, Yotam; Kochba, Efrat; Shukarev, Georgi; Rusch, Sarah; Herrera-Taracena, Guillermo; van Damme, Pierre

2016-10-17

Influenza remains a significant problem in elderly despite widespread vaccination coverage. This randomized, phase-I study in elderly compared different strategies of improving vaccine immunogenicity. A total of 370 healthy participants (⩾65years) were randomized equally 1:1:1:1:1:1 to six influenza vaccine treatments (approximately 60-63 participants per treatment arm) at day 1 that consisted of three investigational virosomal vaccine formulations at doses of 7.5, 15, and 45μg HA antigen/strain administered intradermally (ID) by MicronJet600™ microneedle device (NanoPass Technologies) or intramuscularly (IM), and three comparator registered seasonal vaccines; Inflexal V™ (Janssen) and MF59 adjuvanted Fluad™ (Novartis) administered IM and Intanza™ (Sanofi Pasteur) administered ID via Soluvia™ prefilled microinjection system (BD). Serological evaluations were performed at days 22 and 90 and safety followed-up for 6months. Intradermal delivery of virosomal vaccine using MicronJet600™ resulted in significantly higher immunogenicity than the equivalent dose of virosomal Inflexal V™ administered intramuscularly across most of the parameters and strains, as well as in some of the readouts and strains as compared with the 45μg dose of virosomal vaccine formulation. Of 370 participants, 300 (81.1%) reported ⩾1 adverse event (AE); more participants reported solicited local AEs (72.2%) than solicited systemic AEs (12.2%). Intradermal delivery significantly improved influenza vaccine immunogenicity compared with intramuscular delivery. Triple dose (45μg) virosomal vaccine did not demonstrate any benefit on vaccine's immunogenicity over 15μg commercial presentation. All treatments were generally safe and well-tolerated. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Dendrimer-conjugated peptide vaccine enhances clearance of Chlamydia trachomatis genital infection.

Science.gov (United States)

Ganda, Ingrid S; Zhong, Qian; Hali, Mirabela; Albuquerque, Ricardo L C; Padilha, Francine F; da Rocha, Sandro R P; Whittum-Hudson, Judith A

2017-07-15

Peptide-based vaccines have emerged in recent years as promising candidates in the prevention of infectious diseases. However, there are many challenges to maintaining in vivo peptide stability and enhancement of peptide immunogenicity to generate protective immunity which enhances clearance of infections. Here, a dendrimer-based carrier system is proposed for peptide-based vaccine delivery, and shows its anti-microbial feasibility in a mouse model of Chlamydia trachomatis. Chlamydiae are the most prevalent sexually transmitted bacteria worldwide, and also the causal agent of trachoma, the leading cause of preventable infectious blindness. In spite of the prevalence of this infectious agent and the many previous vaccine-related studies, there is no vaccine commercially available. The carrier system proposed consists of generation 4, hydroxyl-terminated, polyamidoamine (PAMAM) dendrimers (G4OH), to which a peptide mimic of a chlamydial glycolipid antigen-Peptide 4 (Pep4, AFPQFRSATLLL) was conjugated through an ester bond. The ester bond between G4OH and Pep4 is expected to break down mainly in the intracellular environment for antigen presentation. Pep4 conjugated to dendrimer induced Chlamydia-specific serum antibodies after subcutaneous immunizations. Further, this new vaccine formulation significantly protected immunized animals from vaginal challenge with infectious Chlamydia trachomatis, and it reduced infectious loads and tissue (genital tract) damage. Pep4 conjugated to G4OH or only mixed with peptide provided enhanced protection compared to Pep4 and adjuvant (i.e. alum), suggesting a potential adjuvant effect of the PAMAM dendrimer. Combined, these results demonstrate that hydroxyl-terminated PAMAM dendrimer is a promising polymeric nanocarrier platform for the delivery of peptide vaccines and this approach has potential to be expanded to other infectious intracellular bacteria and viruses of public health significance. Copyright © 2017 Elsevier B.V. All

Nanoengineering of vaccines using natural polysaccharides.

Science.gov (United States)

Cordeiro, Ana Sara; Alonso, María José; de la Fuente, María

2015-11-01

Currently, there are over 70 licensed vaccines, which prevent the pathogenesis of around 30 viruses and bacteria. Nevertheless, there are still important challenges in this area, which include the development of more active, non-invasive, and thermo-resistant vaccines. Important biotechnological advances have led to safer subunit antigens, such as proteins, peptides, and nucleic acids. However, their limited immunogenicity has demanded potent adjuvants that can strengthen the immune response. Particulate nanocarriers hold a high potential as adjuvants in vaccination. Due to their pathogen-like size and structure, they can enhance immune responses by mimicking the natural infection process. Additionally, they can be tailored for non-invasive mucosal administration (needle-free vaccination), and control the delivery of the associated antigens to a specific location and for prolonged times, opening room for single-dose vaccination. Moreover, they allow co-association of immunostimulatory molecules to improve the overall adjuvant capacity. The natural and ubiquitous character of polysaccharides, together with their intrinsic immunomodulating properties, their biocompatibility, and biodegradability, justify their interest in the engineering of nanovaccines. In this review, we aim to provide a state-of-the-art overview regarding the application of nanotechnology in vaccine delivery, with a focus on the most recent advances in the development and application of polysaccharide-based antigen nanocarriers. Copyright © 2015 Elsevier Inc. All rights reserved.

Supersaturating drug delivery systems

DEFF Research Database (Denmark)

Laitinen, Riikka; Löbmann, Korbinian; Grohganz, Holger

2017-01-01

of the bioavailability of poorly water-soluble drugs by increasing the driving force for drug absorption. However, ASDs often require a high weight percentage of carrier (usually a hydrophilic polymer) to ensure molecular mixing of the drug in the carrier and stabilization of the supersaturated state, often leading......Amorphous solid dispersions (ASDs) are probably the most common and important supersaturating drug delivery systems for the formulation of poorly water-soluble compounds. These delivery systems are able to achieve and maintain a sustained drug supersaturation which enables improvement...... strategy for poorly-soluble drugs. While the current research on co-amorphous formulations is focused on preparation and characterization of these systems, more detailed research on their supersaturation and precipitation behavior and the effect of co-formers on nucleation and crystal growth inhibition...

Vaccination of carp against SVCV with an oral DNA vaccine or an insect cells-based subunit vaccine.

Science.gov (United States)

Embregts, C W E; Rigaudeau, D; Tacchi, L; Pijlman, G P; Kampers, L; Veselý, T; Pokorová, D; Boudinot, P; Wiegertjes, G F; Forlenza, M

2018-03-19

We recently reported on a successful vaccine for carp against SVCV based on the intramuscular injection of a DNA plasmid encoding the SVCV glycoprotein (SVCV-G). This shows that the intramuscular (i.m.) route of vaccination is suitable to trigger protective responses against SVCV, and that the SVCV G-protein is a suitable vaccine antigen. Yet, despite the general success of DNA vaccines, especially against fish rhabdoviruses, their practical implementation still faces legislative as well as consumer's acceptance concerns. Furthermore, the i.m. route of plasmid administration is not easily combined with most of the current vaccination regimes largely based on intraperitoneal or immersion vaccination. For this reason, in the current study we evaluated possible alternatives to a DNA-based i.m. injectable vaccine using the SVCV-G protein as the vaccine antigen. To this end, we tested two parallel approaches: the first based on the optimization of an alginate encapsulation method for oral delivery of DNA and protein antigens; the second based on the baculovirus recombinant expression of transmembrane SVCV-G protein in insect cells, administered as whole-cell subunit vaccine through the oral and injection route. In addition, in the case of the oral DNA vaccine, we also investigated the potential benefits of the mucosal adjuvants Escherichia coli lymphotoxin subunit B (LTB). Despite the use of various vaccine types, doses, regimes, and administration routes, no protection was observed, contrary to the full protection obtained with our reference i.m. DNA vaccine. The limited protection observed under the various conditions used in this study, the nature of the host, of the pathogen, the type of vaccine and encapsulation method, will therefore be discussed in details to provide an outlook for future vaccination strategies against SVCV. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Methods and metrics challenges of delivery-system research

Directory of Open Access Journals (Sweden)

Alexander Jeffrey A

2012-03-01

Full Text Available Abstract Background Many delivery-system interventions are fundamentally about change in social systems (both planned and unplanned. This systems perspective raises a number of methodological challenges for studying the effects of delivery-system change--particularly for answering questions related to whether the change will work under different conditions and how the change is integrated (or not into the operating context of the delivery system. Methods The purpose of this paper is to describe the methodological and measurement challenges posed by five key issues in delivery-system research: (1 modeling intervention context; (2 measuring readiness for change; (3 assessing intervention fidelity and sustainability; (4 assessing complex, multicomponent interventions; and (5 incorporating time in delivery-system models to discuss recommendations for addressing these issues. For each issue, we provide recommendations for how research may be designed and implemented to overcome these challenges. Results and conclusions We suggest that a more refined understanding of the mechanisms underlying delivery-system interventions (treatment theory and the ways in which outcomes for different classes of individuals change over time are fundamental starting points for capturing the heterogeneity in samples of individuals exposed to delivery-system interventions. To support the research recommendations outlined in this paper and to advance understanding of the "why" and "how" questions of delivery-system change and their effects, funding agencies should consider supporting studies with larger organizational sample sizes; longer duration; and nontraditional, mixed-methods designs. A version of this paper was prepared under contract with the Agency for Healthcare Research and Quality (AHRQ, US Department of Health and Human Services for presentation and discussion at a meeting on "The Challenge and Promise of Delivery System Research," held in Sterling, VA, on

Lipid-formulated bcg as an oral-bait vaccine for tuberculosis: vaccine stability, efficacy, and palatability to brushtail possums (Trichosurus vulpecula) in New Zealand.

Science.gov (United States)

Cross, Martin L; Henderson, Ray J; Lambeth, Matthew R; Buddle, Bryce M; Aldwell, Frank E

2009-07-01

Bovine tuberculosis (Tb), due to infection with virulent Mycobacterium bovis, represents a threat to New Zealand agriculture due to vectorial transmission from wildlife reservoir species, principally the introduced Australian brushtail possum (Trichosurus vulpecula). An oral-delivery wildlife vaccine has been developed to immunize possums against Tb, based on formulation of the human Tb vaccine (M. bovis BCG) in edible lipid matrices. Here BCG bacilli were shown to be stable in lipid matrix formulation for over 8 mo in freezer storage, for 7 wk under room temperature conditions, and for 3-5 wk under field conditions in a forest/pasture margin habitat (when maintained in weatherproof bait-delivery sachets). Samples of the lipid matrix were flavored and offered to captive possums in a bait-preference study: a combination of 10% chocolate powder with anise oil was identified as the most effective attractant/palatability combination. In a replicated field study, 85-100% of wild possums were shown to access chocolate-flavored lipid pellets, when baits were applied to areas holding approximately 600-800 possums/km(2). Finally, in a controlled vaccination/challenge study, chocolate-flavored lipid vaccine samples containing 10(8) BCG bacilli were fed to captive possums, which were subsequently challenged via aerosol exposure to virulent M. bovis: vaccine immunogenicity was confirmed, and protection was identified by significantly reduced postchallenge weight loss in vaccinated animals compared to nonvaccinated controls. These studies indicate that, appropriately flavored, lipid delivery matrices may form effective bait vaccines for the control of Tb in wildlife.

Virus-Vectored Influenza Virus Vaccines

Science.gov (United States)

Tripp, Ralph A.; Tompkins, S. Mark

2014-01-01

Despite the availability of an inactivated vaccine that has been licensed for >50 years, the influenza virus continues to cause morbidity and mortality worldwide. Constant evolution of circulating influenza virus strains and the emergence of new strains diminishes the effectiveness of annual vaccines that rely on a match with circulating influenza strains. Thus, there is a continued need for new, efficacious vaccines conferring cross-clade protection to avoid the need for biannual reformulation of seasonal influenza vaccines. Recombinant virus-vectored vaccines are an appealing alternative to classical inactivated vaccines because virus vectors enable native expression of influenza antigens, even from virulent influenza viruses, while expressed in the context of the vector that can improve immunogenicity. In addition, a vectored vaccine often enables delivery of the vaccine to sites of inductive immunity such as the respiratory tract enabling protection from influenza virus infection. Moreover, the ability to readily manipulate virus vectors to produce novel influenza vaccines may provide the quickest path toward a universal vaccine protecting against all influenza viruses. This review will discuss experimental virus-vectored vaccines for use in humans, comparing them to licensed vaccines and the hurdles faced for licensure of these next-generation influenza virus vaccines. PMID:25105278

Vaccines 'on demand': science fiction or a future reality.

Science.gov (United States)

Ulmer, Jeffrey B; Mansoura, Monique K; Geall, Andrew J

2015-02-01

Self-amplifying mRNA vaccines are being developed as a platform technology with potential to be used for a broad range of targets. The synthetic production methods for their manufacture, combined with the modern tools of bioinformatics and synthetic biology, enable these vaccines to be produced rapidly from an electronic gene sequence. Preclinical proof of concept has so far been achieved for influenza, respiratory syncytial virus, rabies, Ebola, cytomegalovirus, human immunodeficiency virus and malaria. This editorial highlights the key milestones in the discovery and development of self-amplifying mRNA vaccines, and reviews how they might be used as a rapid response platform. The paper points out how future improvements in RNA vector design and non-viral delivery may lead to decreases in effective dose and increases in production capacity. The prospects for non-viral delivery of self-amplifying mRNA vaccines are very promising. Like other types of nucleic acid vaccines, these vaccines have the potential to draw on the positive attributes of live-attenuated vaccines while obviating many potential safety limitations. Hence, this approach could enable the concept of vaccines on demand as a rapid response to a real threat rather than the deployment of strategic stockpiles based on epidemiological predictions for possible threats.

Use of geographic information systems in rabies vaccination campaigns.

Science.gov (United States)

Grisi-Filho, José Henrique de Hildebrand e; Amaku, Marcos; Dias, Ricardo Augusto; Montenegro Netto, Hildebrando; Paranhos, Noemia Tucunduva; Mendes, Maria Cristina Novo Campos; Ferreira Neto, José Soares; Ferreira, Fernando

2008-12-01

To develop a method to assist in the design and assessment of animal rabies control campaigns. A methodology was developed based on geographic information systems to estimate the animal (canine and feline) population and density per census tract and per subregion (known as "Subprefeituras") in the city of São Paulo (Southeastern Brazil) in 2002. The number of vaccination units in a given region was estimated to achieve a certain proportion of vaccination coverage. Census database was used for the human population, as well as estimates ratios of dog:inhabitant and cat:inhabitant. Estimated figures were 1,490,500 dogs and 226,954 cats in the city, i.e. an animal population density of 1138.14 owned animals per km(2). In the 2002 campaign, 926,462 were vaccinated, resulting in a vaccination coverage of 54%. The estimated number of vaccination units to be able to reach a 70%-vaccination coverage, by vaccinating 700 animals per unit on average, was 1,729. These estimates are presented as maps of animal density according to census tracts and "Subprefeituras". The methodology used in the study may be applied in a systematic way to the design and evaluation of rabies vaccination campaigns, enabling the identification of areas of critical vaccination coverage.

Recent Trends of Polymer Mediated Liposomal Gene Delivery System

Directory of Open Access Journals (Sweden)

Shyamal Kumar Kundu

2014-01-01

Full Text Available Advancement in the gene delivery system have resulted in clinical successes in gene therapy for patients with several genetic diseases, such as immunodeficiency diseases, X-linked adrenoleukodystrophy (X-ALD blindness, thalassemia, and many more. Among various delivery systems, liposomal mediated gene delivery route is offering great promises for gene therapy. This review is an attempt to depict a portrait about the polymer based liposomal gene delivery systems and their future applications. Herein, we have discussed in detail the characteristics of liposome, importance of polymer for liposome formulation, gene delivery, and future direction of liposome based gene delivery as a whole.

Developments in the formulation and delivery of spray dried vaccines

NARCIS (Netherlands)

Kanojia, Gaurav; Have, Rimko Ten; Soema, Peter C; Frijlink, Henderik; Amorij, Jean-Pierre; Kersten, Gideon

2017-01-01

Spray drying is a promising method for the stabilization of vaccines, which are usually formulated as liquids. Usually, vaccine stability is improved by spray drying in the presence of a range of excipients. Unlike freeze drying, there is no freezing step involved, thus the damage related to this

Modified thermoresponsive Poloxamer 407 and chitosan sol-gels as potential sustained-release vaccine delivery systems

DEFF Research Database (Denmark)

Kojarunchitt, Thunjiradasiree; Baldursdottir, Stefania; Dong, Yao-Da

2015-01-01

Thermoresponsive, particle-loaded, Poloxamer 407 (P407)-Pluronic-R® (25R4) or chitosan-methyl cellulose (MC) formulations were developed as single-dose, sustained release vaccines. The sol-gels, loaded either with a particulate vaccine (cubosomes) or soluble antigen (ovalbumin) and adjuvants (Quil...... the chitosan-MC sol-gels sustained the release of antigen up to at least 14 days after administration. The chitosan-MC sol-gels stimulated both cellular and humoral responses. The inclusion of cubosomes in the sol-gels did not provide a definitive beneficial effect. Further analysis of the formulations...... with small-angle X-ray scattering (SAXS) revealed that while cubosomes were stable in chitosan-MC gels they were not stable in P407-25R4 formulations. The reason for the mixed response to cubosome-loaded vehicles requires more investigation, however it appears that the cubosomes did not facilitate...

Aspergillus vaccines: Hardly worth studying or worthy of hard study?

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Levitz, Stuart M

2017-01-01

Vaccines rank among the greatest advances in the history of public health. Yet, despite the need, there are no licensed vaccines to protect humans against fungal diseases, including aspergillosis. In this focused review, some of the major scientific and logistical challenges to developing vaccines to protect at-risk individuals against aspergillosis are discussed. Approaches that have shown promise in animal models include vaccines that protect against multiple fungal genera and those that are specifically directed to Aspergillus Advances in proteomics and glycomics have facilitated identification of candidate antigens for use in subunit vaccines. Novel adjuvants and delivery systems are becoming available that can skew vaccine responses toward those associated with protection. Immunotherapy consisting of adoptive transfer of Aspergillus-specific T cells to allogeneic hematopoietic transplant recipients has advanced to human testing but is technically difficult and of unproven benefit. While progress has been impressive, much work still needs to be done if vaccines against aspergillosis are to become a reality. © The Author 2016. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Transdermal influenza immunization with vaccine-coated microneedle arrays.

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Dimitrios G Koutsonanos

Full Text Available Influenza is a contagious disease caused by a pathogenic virus, with outbreaks all over the world and thousands of hospitalizations and deaths every year. Due to virus antigenic drift and short-lived immune responses, annual vaccination is required. However, vaccine coverage is incomplete, and improvement in immunization is needed. The objective of this study is to investigate a novel method for transdermal delivery using metal microneedle arrays (MN coated with inactivated influenza virus to determine whether this route is a simpler and safer approach than the conventional immunization, capable to induce robust immune responses and confer protection against lethal virus challenge.Inactivated A/Aichi/2/68 (H3N2 influenza virus was coated on metal microneedle arrays and applied to mice as a vaccine in the caudal dorsal skin area. Substantial antibody titers with hemagglutination inhibition activity were detected in sera collected two and four weeks after a single vaccine dose. Challenge studies in mice with 5 x LD(50 of mouse adapted Aichi virus demonstrated complete protection. Microneedle vaccination induced a broad spectrum of immune responses including CD4+ and CD8+ responses in the spleen and draining lymph node, a high frequency of antigen-secreting cells in the lung and induction of virus-specific memory B-cells. In addition, the use of MN showed a dose-sparing effect and a strong Th2 bias when compared to an intramuscular (IM reference immunization.The present results show that delivery of inactivated influenza virus through the skin using metal microneedle arrays induced strong humoral and cellular immune responses capable of conferring protection against virus challenge as efficiently as intramuscular immunization, which is the standard vaccination route. In view of the convenience of delivery and the potential for self-administration, vaccine-coated metal microneedles may provide a novel and highly effective immunization method.

Implementation research: reactive mass vaccination with single-dose oral cholera vaccine, Zambia.

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Poncin, Marc; Zulu, Gideon; Voute, Caroline; Ferreras, Eva; Muleya, Clara Mbwili; Malama, Kennedy; Pezzoli, Lorenzo; Mufunda, Jacob; Robert, Hugues; Uzzeni, Florent; Luquero, Francisco J; Chizema, Elizabeth; Ciglenecki, Iza

2018-02-01

To describe the implementation and feasibility of an innovative mass vaccination strategy - based on single-dose oral cholera vaccine - to curb a cholera epidemic in a large urban setting. In April 2016, in the early stages of a cholera outbreak in Lusaka, Zambia, the health ministry collaborated with Médecins Sans Frontières and the World Health Organization in organizing a mass vaccination campaign, based on single-dose oral cholera vaccine. Over a period of 17 days, partners mobilized 1700 health ministry staff and community volunteers for community sensitization, social mobilization and vaccination activities in 10 townships. On each day, doses of vaccine were delivered to vaccination sites and administrative coverage was estimated. Overall, vaccination teams administered 424 100 doses of vaccine to an estimated target population of 578 043, resulting in an estimated administrative coverage of 73.4%. After the campaign, few cholera cases were reported and there was no evidence of the disease spreading within the vaccinated areas. The total cost of the campaign - 2.31 United States dollars (US$) per dose - included the relatively low cost of local delivery - US$ 0.41 per dose. We found that an early and large-scale targeted reactive campaign using a single-dose oral vaccine, organized in response to a cholera epidemic within a large city, to be feasible and appeared effective. While cholera vaccines remain in short supply, the maximization of the number of vaccines in response to a cholera epidemic, by the use of just one dose per member of an at-risk community, should be considered.

Valuing vaccination.

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Bärnighausen, Till; Bloom, David E; Cafiero-Fonseca, Elizabeth T; O'Brien, Jennifer Carroll

2014-08-26

Vaccination has led to remarkable health gains over the last century. However, large coverage gaps remain, which will require significant financial resources and political will to address. In recent years, a compelling line of inquiry has established the economic benefits of health, at both the individual and aggregate levels. Most existing economic evaluations of particular health interventions fail to account for this new research, leading to potentially sizable undervaluation of those interventions. In line with this new research, we set forth a framework for conceptualizing the full benefits of vaccination, including avoided medical care costs, outcome-related productivity gains, behavior-related productivity gains, community health externalities, community economic externalities, and the value of risk reduction and pure health gains. We also review literature highlighting the magnitude of these sources of benefit for different vaccinations. Finally, we outline the steps that need to be taken to implement a broad-approach economic evaluation and discuss the implications of this work for research, policy, and resource allocation for vaccine development and delivery.

Immunization delivery in British Columbia

Science.gov (United States)

Omura, John; Buxton, Jane; Kaczorowski, Janusz; Catterson, Jason; Li, Jane; Derban, Andrea; Hasselback, Paul; Machin, Shelagh; Linekin, Michelle; Morgana, Tamsin; O’Briain, Barra; Scheifele, David; Dawar, Meena

2014-01-01

Abstract Objective To explore the experiences of family physicians and pediatricians delivering immunizations, including perceived barriers and supports. Design Qualitative study using focus groups. Setting Ten cities throughout British Columbia. Participants A total of 46 family physicians or general practitioners, 10 pediatricians, and 2 residents. Methods A semistructured dialogue guide was used by a trained facilitator to explore participants’ experiences and views related to immunization delivery in British Columbia. Verbatim transcriptions were independently coded by 2 researchers. Key themes were analyzed and identified in an iterative manner using interpretive description. Main findings Physicians highly valued vaccine delivery. Factors facilitating physician-delivered immunizations included strong beliefs in the value of vaccines and having adequate information. Identified barriers included the large time commitment and insufficient communication about program changes, new vaccines, and the adult immunization program in general. Some physicians reported good relationships with local public health, while others reported the opposite experience, and this varied by geographic location. Conclusion These findings suggest that physicians are supportive of delivering vaccines. However, there are opportunities to improve the sustainability of physician-delivered immunizations. While compensation schemes remain under the purview of the provincial governments, local public health authorities can address the information needs of physicians. PMID:24627403

Delivery arrangements for health systems in low-income countries: an overview of systematic reviews

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Ciapponi, Agustín; Lewin, Simon; Herrera, Cristian A; Opiyo, Newton; Pantoja, Tomas; Paulsen, Elizabeth; Rada, Gabriel; Wiysonge, Charles S; Bastías, Gabriel; Dudley, Lilian; Flottorp, Signe; Gagnon, Marie-Pierre; Garcia Marti, Sebastian; Glenton, Claire; Okwundu, Charles I; Peñaloza, Blanca; Suleman, Fatima; Oxman, Andrew D

2017-01-01

. Information and communication technology: mobile phone messaging for patients with long-term illnesses, mobile phone messaging reminders for attendance at healthcare appointments, mobile phone messaging to promote adherence to antiretroviral therapy, women carrying their own case notes in pregnancy, interventions to improve childhood vaccination. Quality and safety systems: decision support with clinical information systems for people living with HIV/AIDS. Complex interventions (cutting across delivery categories and other health system arrangements): emergency obstetric referral interventions. Authors' conclusions A wide range of strategies have been evaluated for improving delivery arrangements in low-income countries, using sound systematic review methods in both Cochrane and non-Cochrane reviews. These reviews have assessed a range of outcomes. Most of the available evidence focuses on who provides care, where care is provided and coordination of care. For all the main categories of delivery arrangements, we identified gaps in primary research related to uncertainty about the applicability of the evidence to low-income countries, low- or very low-certainty evidence or a lack of studies. Effects of delivery arrangements for health systems in low-income countries What is the aim of this overview? The aim of this Cochrane Overview is to provide a broad summary of what is known about the effects of delivery arrangements for health systems in low-income countries. This overview is based on 51 systematic reviews. These systematic reviews searched for studies that evaluated different types of delivery arrangements. The reviews included a total of 850 studies. This overview is one of a series of four Cochrane Overviews that evaluate health system arrangements. What was studied in the overview? Delivery arrangements include changes in who receives care and when, who provides care, the working conditions of those who provide care, coordination of care amongst different health care

Updates on the web-based VIOLIN vaccine database and analysis system.

Science.gov (United States)

He, Yongqun; Racz, Rebecca; Sayers, Samantha; Lin, Yu; Todd, Thomas; Hur, Junguk; Li, Xinna; Patel, Mukti; Zhao, Boyang; Chung, Monica; Ostrow, Joseph; Sylora, Andrew; Dungarani, Priya; Ulysse, Guerlain; Kochhar, Kanika; Vidri, Boris; Strait, Kelsey; Jourdian, George W; Xiang, Zuoshuang

2014-01-01

The integrative Vaccine Investigation and Online Information Network (VIOLIN) vaccine research database and analysis system (http://www.violinet.org) curates, stores, analyses and integrates various vaccine-associated research data. Since its first publication in NAR in 2008, significant updates have been made. Starting from 211 vaccines annotated at the end of 2007, VIOLIN now includes over 3240 vaccines for 192 infectious diseases and eight noninfectious diseases (e.g. cancers and allergies). Under the umbrella of VIOLIN, >10 relatively independent programs are developed. For example, Protegen stores over 800 protective antigens experimentally proven valid for vaccine development. VirmugenDB annotated over 200 'virmugens', a term coined by us to represent those virulence factor genes that can be mutated to generate successful live attenuated vaccines. Specific patterns were identified from the genes collected in Protegen and VirmugenDB. VIOLIN also includes Vaxign, the first web-based vaccine candidate prediction program based on reverse vaccinology. VIOLIN collects and analyzes different vaccine components including vaccine adjuvants (Vaxjo) and DNA vaccine plasmids (DNAVaxDB). VIOLIN includes licensed human vaccines (Huvax) and veterinary vaccines (Vevax). The Vaccine Ontology is applied to standardize and integrate various data in VIOLIN. VIOLIN also hosts the Ontology of Vaccine Adverse Events (OVAE) that logically represents adverse events associated with licensed human vaccines.

Vaccines: from valuation to resource allocation.

Science.gov (United States)

Bloom, David E; Madhavan, Guruprasad

2015-06-08

This review focuses on selected challenges and opportunities concerning broader valuation of vaccines and immunization. The challenges involve conceptualizing and measuring the value of vaccines, while the opportunities relate to the strategic and systematic use of that information in health policy decisions that range from the adoption of particular vaccines in national immunization plans to the allocation of resources to vaccine research, development, and delivery. Clarifying the demonstrable individual, family, and community-level benefits of vaccines will allow the public health community to make better-informed and more meaningful comparisons of the costs of vaccines in relation to their full benefits. Taking advantage of this opportunity will require enhanced data collection and the development of strategic planning tools for transparently assessing trade-offs among the myriad attributes of different vaccines in various social and economic contexts. Copyright © 2015 Elsevier Ltd. All rights reserved.

Stimuli-Responsive Polymeric Systems for Controlled Protein and Peptide Delivery: Future Implications for Ocular Delivery.

Science.gov (United States)

Mahlumba, Pakama; Choonara, Yahya E; Kumar, Pradeep; du Toit, Lisa C; Pillay, Viness

2016-07-30

Therapeutic proteins and peptides have become notable in the drug delivery arena for their compatibility with the human body as well as their high potency. However, their biocompatibility and high potency does not negate the existence of challenges resulting from physicochemical properties of proteins and peptides, including large size, short half-life, capability to provoke immune responses and susceptibility to degradation. Various delivery routes and delivery systems have been utilized to improve bioavailability, patient acceptability and reduce biodegradation. The ocular route remains of great interest, particularly for responsive delivery of macromolecules due to the anatomy and physiology of the eye that makes it a sensitive and complex environment. Research in this field is slowly gaining attention as this could be the breakthrough in ocular drug delivery of macromolecules. This work reviews stimuli-responsive polymeric delivery systems, their use in the delivery of therapeutic proteins and peptides as well as examples of proteins and peptides used in the treatment of ocular disorders. Stimuli reviewed include pH, temperature, enzymes, light, ultrasound and magnetic field. In addition, it discusses the current progress in responsive ocular drug delivery. Furthermore, it explores future prospects in the use of stimuli-responsive polymers for ocular delivery of proteins and peptides. Stimuli-responsive polymers offer great potential in improving the delivery of ocular therapeutics, therefore there is a need to consider them in order to guarantee a local, sustained and ideal delivery of ocular proteins and peptides, evading tissue invasion and systemic side-effects.

Antibody response in animals immunized after oral delivery of attenuated liver hepatitis a vaccine

International Nuclear Information System (INIS)

Long Runxiang; Hou Zongliu; Xie Zhongping; Ding Xuefeng; Pan Yue; Huang Cheng; Zhang Ming; Yang Lixian

2006-01-01

The microspheres were prepared by encapsulating live attenuated hepatitis A vaccine with PLA/PLG, and the rhesus monkeys and mice were immunized by such microspheres through oral route. Then serum was collected to detect the HAV-IgM, HAV-IgG, HAV-IgA with EIA, so as to find a convenient immunization way. Results showed that HAV-IgG in rhesus monkeys was detected in the 3rd week and reached a peak value (1267mlU/mL), and then decreased by degrees. HAV-IgM titer was 1:4000. After an oral booster was given, the HAV-IgG level increased, and HAV-IgM titer was 1:1000. The level reached 1244mIU/mL after challenge with wild virus strain, and HAV-IgM was 1:100. HAV-IgM was detected in the control group only after challenge with wild virus strain. HAV-IgG in mice was detected in the 2nd week and reached a peak value in the 4th week. HAV S-IgA was detected in the 1st week and reached a peak value in the 4th week. Antibody response was induced in the rhesus monkeys after oral delivery of the biodegradable microspheres containing live attenuated HA vaccine. The results in mice were similar with the report but the anti-HAV was present earlier as compared with rhesus monkeys. (authors)

Solid lipid nanoparticles mediate non-viral delivery of plasmid DNA to dendritic cells

Science.gov (United States)

Penumarthi, Alekhya; Parashar, Deepti; Abraham, Amanda N.; Dekiwadia, Chaitali; Macreadie, Ian; Shukla, Ravi; Smooker, Peter M.

2017-06-01

There is an increasing demand for novel DNA vaccine delivery systems, mainly for the non-viral type as they are considered relatively safe. Therefore, solid lipid nanoparticles (SLNs) were investigated for their suitability as a non-viral DNA vaccine delivery system. SLNs were synthesised by a modified solvent-emulsification method in order to study their potential to conjugate with plasmid DNA and deliver them in vitro to dendritic cells using eGFP as the reporter plasmid. The DNA-SLN complexes were characterised by electron microscopy, gel retardation assays and dynamic light scattering. The cytotoxicity assay data supported their biocompatibility and was used to estimate safe threshold concentration resulting in high transfection rate. The transfection efficiency of these complexes in a dendritic cell line was shown to increase significantly compared to plasmid alone, and was comparable to that mediated by lipofectamine. Transmission electron microscopy studies delineated the pathway of cellular uptake. Endosomal escape was observed supporting the mechanism of transfection.

Preparation of alginate coated chitosan microparticles for vaccine delivery

Directory of Open Access Journals (Sweden)

Wei YuQuan

2008-11-01

Full Text Available Abstract Background Absorption of antigens onto chitosan microparticles via electrostatic interaction is a common and relatively mild process suitable for mucosal vaccine. In order to increase the stability of antigens and prevent an immediate desorption of antigens from chitosan carriers in gastrointestinal tract, coating onto BSA loaded chitosan microparticles with sodium alginate was performed by layer-by-layer technology to meet the requirement of mucosal vaccine. Results The prepared alginate coated BSA loaded chitosan microparticles had loading efficiency (LE of 60% and loading capacity (LC of 6% with mean diameter of about 1 μm. When the weight ratio of alginate/chitosan microparticles was greater than 2, the stable system could be obtained. The rapid charge inversion of BSA loaded chitosan microparticles (from +27 mv to -27.8 mv was observed during the coating procedure which indicated the presence of alginate layer on the chitosan microparticles surfaces. According to the results obtained by scanning electron microscopy (SEM, the core-shell structure of BSA loaded chitosan microparticles was observed. Meanwhile, in vitro release study indicated that the initial burst release of BSA from alginate coated chitosan microparticles was lower than that observed from uncoated chitosan microparticles (40% in 8 h vs. about 84% in 0.5 h. SDS-polyacrylamide gel electrophoresis (SDS-PAGE assay showed that alginate coating onto chitosan microparticles could effectively protect the BSA from degradation or hydrolysis in acidic condition for at least 2 h. The structural integrity of alginate modified chitosan microparticles incubated in PBS for 24 h was investigated by FTIR. Conclusion The prepared alginate coated chitosan microparticles, with mean diameter of about 1 μm, was suitable for oral mucosal vaccine. Moreover, alginate coating onto the surface of chitosan microparticles could modulate the release behavior of BSA from alginate coated chitosan

Typhoid fever vaccination strategies.

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Date, Kashmira A; Bentsi-Enchill, Adwoa; Marks, Florian; Fox, Kimberley

2015-06-19

Typhoid vaccination is an important component of typhoid fever prevention and control, and is recommended for public health programmatic use in both endemic and outbreak settings. We reviewed experiences with various vaccination strategies using the currently available typhoid vaccines (injectable Vi polysaccharide vaccine [ViPS], oral Ty21a vaccine, and injectable typhoid conjugate vaccine [TCV]). We assessed the rationale, acceptability, effectiveness, impact and implementation lessons of these strategies to inform effective typhoid vaccination strategies for the future. Vaccination strategies were categorized by vaccine disease control strategy (preemptive use for endemic disease or to prevent an outbreak, and reactive use for outbreak control) and vaccine delivery strategy (community-based routine, community-based campaign and school-based). Almost all public health typhoid vaccination programs used ViPS vaccine and have been in countries of Asia, with one example in the Pacific and one experience using the Ty21a vaccine in South America. All vaccination strategies were found to be acceptable, feasible and effective in the settings evaluated; evidence of impact, where available, was strongest in endemic settings and in the short- to medium-term. Vaccination was cost-effective in high-incidence but not low-incidence settings. Experience in disaster and outbreak settings remains limited. TCVs have recently become available and none are WHO-prequalified yet; no program experience with TCVs was found in published literature. Despite the demonstrated success of several typhoid vaccination strategies, typhoid vaccines remain underused. Implementation lessons should be applied to design optimal vaccination strategies using TCVs which have several anticipated advantages, such as potential for use in infant immunization programs and longer duration of protection, over the ViPS and Ty21a vaccines for typhoid prevention and control. Copyright © 2015. Published by

Humoral Immunity to Primary Smallpox Vaccination: Impact of Childhood versus Adult Immunization on Vaccinia Vector Vaccine Development in Military Populations.

Directory of Open Access Journals (Sweden)

Bonnie M Slike

Full Text Available Modified Vaccinia virus has been shown to be a safe and immunogenic vector platform for delivery of HIV vaccines. Use of this vector is of particular importance to the military, with the implementation of a large scale smallpox vaccination campaign in 2002 in active duty and key civilian personnel in response to potential bioterrorist activities. Humoral immunity to smallpox vaccination was previously shown to be long lasting (up to 75 years and protective. However, using vaccinia-vectored vaccine delivery for other diseases on a background of anti-vector antibodies (i.e. pre-existing immunity may limit their use as a vaccine platform, especially in the military. In this pilot study, we examined the durability of vaccinia antibody responses in adult primary vaccinees in a healthy military population using a standard ELISA assay and a novel dendritic cell neutralization assay. We found binding and neutralizing antibody (NAb responses to vaccinia waned after 5-10 years in a group of 475 active duty military, born after 1972, who were vaccinated as adults with Dryvax®. These responses decreased from a geometric mean titer (GMT of 250 to baseline (30 years with a GMT of 210 (range 112-3234. This data suggests limited durability of antibody responses in adult vaccinees compared to those vaccinated in childhood and further that adult vaccinia recipients may benefit similarly from receipt of a vaccinia based vaccine as those who are vaccinia naïve. Our findings may have implications for the smallpox vaccination schedule and support the ongoing development of this promising viral vector in a military vaccination program.

The Research Progress of Targeted Drug Delivery Systems

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Zhan, Jiayin; Ting, Xizi Liang; Zhu, Junjie

2017-06-01

Targeted drug delivery system (DDS) means to selectively transport drugs to targeted tissues, organs, and cells through a variety of drugs carrier. It is usually designed to improve the pharmacological and therapeutic properties of conventional drugs and to overcome problems such as limited solubility, drug aggregation, poor bio distribution and lack of selectivity, controlling drug release carrier and to reduce normal tissue damage. With the characteristics of nontoxic and biodegradable, it can increase the retention of drug in lesion site and the permeability, improve the concentration of the drug in lesion site. at present, there are some kinds of DDS using at test phase, such as slow controlled release drug delivery system, targeted drug delivery systems, transdermal drug delivery system, adhesion dosing system and so on. This paper makes a review for DDS.

A study on nanodiamond-based drug delivery system

International Nuclear Information System (INIS)

Li Jing; Zhang Xiaoyong; Zhu Ying; Li Wenxin; Huang Qing

2010-01-01

A multifunctional drug delivery system based on nanodiamonds (NDs) has been developed. FITC, HCPT and TF were absorbed on NDs successively to form the multifunctional complex. The NDs and ND complex samples were characterized by TEM, FR-IR and UV-V. The results indicated that this drug delivery system is a high loading system. Efficacy of the drug delivery system on Hela cell was evaluated with MTT assays and fluorescence microscopy. The results show that multifunction of the NDs complex include fluorescence, targeting and high efficacy. (authors)

Analytics for vaccine economics and pricing: insights and observations.

Science.gov (United States)

Robbins, Matthew J; Jacobson, Sheldon H

2015-04-01

Pediatric immunization programs in the USA are a successful and cost-effective public health endeavor, profoundly reducing mortalities caused by infectious diseases. Two important issues relate to the success of the immunization programs, the selection of cost-effective vaccines and the appropriate pricing of vaccines. The recommended childhood immunization schedule, published annually by the CDC, continues to expand with respect to the number of injections required and the number of vaccines available for selection. The advent of new vaccines to meet the growing requirements of the schedule results: in a large, combinatorial number of possible vaccine formularies. The expansion of the schedule and the increase in the number of available vaccines constitutes a challenge for state health departments, large city immunization programs, private practices and other vaccine purchasers, as a cost-effective vaccine formulary must be selected from an increasingly large set of possible vaccine combinations to satisfy the schedule. The pediatric vaccine industry consists of a relatively small number of pharmaceutical firms engaged in the research, development, manufacture and distribution of pediatric vaccines. The number of vaccine manufacturers has dramatically decreased in the past few decades for a myriad of reasons, most notably due to low profitability. The contraction of the industry negatively impacts the reliable provision of pediatric vaccines. The determination of appropriate vaccine prices is an important issue and influences a vaccine manufacturer's decision to remain in the market. Operations research is a discipline that applies advanced analytical methods to improve decision making; analytics is the application of operations research to a particular problem using pertinent data to provide a practical result. Analytics provides a mechanism to resolve the challenges facing stakeholders in the vaccine development and delivery system, in particular, the selection

Systemic RNA delivery to dendritic cells exploits antiviral defence for cancer immunotherapy

Science.gov (United States)

Kranz, Lena M.; Diken, Mustafa; Haas, Heinrich; Kreiter, Sebastian; Loquai, Carmen; Reuter, Kerstin C.; Meng, Martin; Fritz, Daniel; Vascotto, Fulvia; Hefesha, Hossam; Grunwitz, Christian; Vormehr, Mathias; Hüsemann, Yves; Selmi, Abderraouf; Kuhn, Andreas N.; Buck, Janina; Derhovanessian, Evelyna; Rae, Richard; Attig, Sebastian; Diekmann, Jan; Jabulowsky, Robert A.; Heesch, Sandra; Hassel, Jessica; Langguth, Peter; Grabbe, Stephan; Huber, Christoph; Türeci, Özlem; Sahin, Ugur

2016-06-01

Lymphoid organs, in which antigen presenting cells (APCs) are in close proximity to T cells, are the ideal microenvironment for efficient priming and amplification of T-cell responses. However, the systemic delivery of vaccine antigens into dendritic cells (DCs) is hampered by various technical challenges. Here we show that DCs can be targeted precisely and effectively in vivo using intravenously administered RNA-lipoplexes (RNA-LPX) based on well-known lipid carriers by optimally adjusting net charge, without the need for functionalization of particles with molecular ligands. The LPX protects RNA from extracellular ribonucleases and mediates its efficient uptake and expression of the encoded antigen by DC populations and macrophages in various lymphoid compartments. RNA-LPX triggers interferon-α (IFNα) release by plasmacytoid DCs and macrophages. Consequently, DC maturation in situ and inflammatory immune mechanisms reminiscent of those in the early systemic phase of viral infection are activated. We show that RNA-LPX encoding viral or mutant neo-antigens or endogenous self-antigens induce strong effector and memory T-cell responses, and mediate potent IFNα-dependent rejection of progressive tumours. A phase I dose-escalation trial testing RNA-LPX that encode shared tumour antigens is ongoing. In the first three melanoma patients treated at a low-dose level, IFNα and strong antigen-specific T-cell responses were induced, supporting the identified mode of action and potency. As any polypeptide-based antigen can be encoded as RNA, RNA-LPX represent a universally applicable vaccine class for systemic DC targeting and synchronized induction of both highly potent adaptive as well as type-I-IFN-mediated innate immune mechanisms for cancer immunotherapy.

Elastin-Like Recombinamers As Smart Drug Delivery Systems.

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Arias, F Javier; Santos, Mercedes; Ibanez-Fonseca, Arturo; Pina, Maria Jesus; Serrano, Sofía

2018-02-19

Drug delivery systems that are able to control the release of bioactive molecules and designed to carry drugs to target sites are of particular interest for tissue therapy. Moreover, systems comprising materials that can respond to environmental stimuli and promote self-assembly and higher order supramolecular organization are especially useful in the biomedical field. Objetive: This review focuses on biomaterials suitable for this purpose and that include elastin-like recombinamers (ELRs), a class of proteinaceous polymers bioinspired by natural elastin, designed using recombinant technologies. The self-assembly and thermoresponsive behaviour of these systems, along with their biodegradability, biocompatibility and well-defined composition as a result of their tailormade design, make them particularly attractive for controlled drug delivery. ELR-based delivery systems that allow targeted delivery are reviewed, especially ELR-drug recombinant fusion constructs, ELR-drug systems chemically bioconjugated in their monomeric and soluble forms, and drug encapsulation by nanoparticle-forming ELRs. Subsequently, the review focuses on those drug carriers in which smart release is triggered by pH or temperature with a particular focus on cancer treatments. Systems for controlled drug release based on depots and hydrogels that act as both a support and reservoir in which drugs can be stored will be described, and their applications in drug delivery discussed. Finally, smart drug-delivery systems not based on ELRs, including those comprising proteins, synthetic polymers and non-polymeric systems, will also be briefly discussed. Several different constructions based on ELRs are potential candidates for controlled drug delivery to be applied in advanced biomedical treatments. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The status of vaccine availability and associated factors in Tshwane government clinics.

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Ngcobo, Ntombenhle Judith; Kamupira, Mercy G

2017-05-24

Vaccines have greatly contributed to the control of vaccine-preventable diseases and to human development. Efforts by many countries to introduce new vaccines are a significant move towards achieving the sustainable development goal for health. However, effective vaccine supply chains that ensure an uninterrupted supply of vaccines are pivotal to attaining universal access to life-saving vaccines and sustainable development. The introduction of new vaccines puts a strain on supply chains; South Africa (SA) is no exception, as there are indications of vaccine stock-outs in clinics. To establish the status of vaccine availability and associated factors in government health facilities of Tshwane Health District in Gauteng Province, SA. A cross-sectional study was conducted in a sample of randomly selected government clinics in the Tshwane health district of Gauteng Province. Data were collected using a structured measurement instrument in participating clinics. Data were analysed using Excel-based software (Microsoft, USA). A total of 31 clinics participated. In the preceding 12 months, clinics had experienced vaccine stock-outs, especially of the three newer vaccines: pneumococcal conjugate vaccine, rotavirus and Pentaxim. These were also out of stock for a long duration; for over 2 weeks in a majority of clinics. The causes of vaccine stock-outs were: poor management of stock, district depot out of stock, unreliable deliveries, lack of pharmacy assistants and limited fridge capacity. Further burdening the situation is the ineffective emergency-ordering system. Significant shortages of vaccines, which are essential drugs, occur in Tshwane government clinics. Vaccine supply chain issues and vaccine shortages should be treated as a priority at all levels of the healthcare system; therefore, a similar study should be conducted at national level. It is recommended that the vaccine supply chain should be restructured and overhauled with the use of advances in technology

Peptide Vaccine: Progress and Challenges

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Weidang Li

2014-07-01

Full Text Available Conventional vaccine strategies have been highly efficacious for several decades in reducing mortality and morbidity due to infectious diseases. The bane of conventional vaccines, such as those that include whole organisms or large proteins, appear to be the inclusion of unnecessary antigenic load that, not only contributes little to the protective immune response, but complicates the situation by inducing allergenic and/or reactogenic responses. Peptide vaccines are an attractive alternative strategy that relies on usage of short peptide fragments to engineer the induction of highly targeted immune responses, consequently avoiding allergenic and/or reactogenic sequences. Conversely, peptide vaccines used in isolation are often weakly immunogenic and require particulate carriers for delivery and adjuvanting. In this article, we discuss the specific advantages and considerations in targeted induction of immune responses by peptide vaccines and progresses in the development of such vaccines against various diseases. Additionally, we also discuss the development of particulate carrier strategies and the inherent challenges with regard to safety when combining such technologies with peptide vaccines.

A genetically engineered prime-boost vaccination strategy for oculonasal delivery with poly(D,L-lactic-co-glycolic acid) microparticles against infection of turkeys with avian Metapneumovirus.

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Liman, Martin; Peiser, Lieselotte; Zimmer, Gert; Pröpsting, Marcus; Naim, Hassan Y; Rautenschlein, Silke

2007-11-14

In this study we demonstrated the use of an oculonasally delivered poly(D,L-lactic-co-glycolic acid) microparticle (PLGA-MP)-based and genetically engineered vaccination strategy in the avian system. An avian Metapneumovirus (aMPV) fusion (F) protein-encoding plasmid vaccine and the corresponding recombinant protein vaccine were produced and bound to or encapsulated by PLGA-MP, respectively. The PLGA-MP as the controlled release system was shown in vitro to not induce any cytopathic effects and to efficiently deliver the F protein-based aMPV-vaccines to avian cells for further processing. Vaccination of turkeys was carried out by priming with an MP-bound F protein-encoding plasmid vaccine and a booster-vaccination with an MP-encapsulated recombinant F protein. Besides the prime-boost F-specific vaccinated birds, negative control birds inoculated with a mock-MP prime-boost regimen as well as non-vaccinated birds and live vaccinated positive control birds were included in the study. The MP-based immunization of turkeys via the oculonasal route induced systemic humoral immune reactions as well as local and systemic cellular immune reactions, and had no adverse effects on the upper respiratory tract. The F protein-specific prime-boost strategy induced partial protection. After challenge the F protein-specific MP-vaccinated birds showed less clinical signs and histopathological lesions than control birds of mock MP-vaccinated and non-vaccinated groups did. The vaccination improved viral clearance and induced accumulation of local and systemic CD4+ T cells when compared to the mock MP-vaccination. It also induced systemic aMPV-neutralizing antibodies. The comparison of mock- and F protein-specific MP-vaccinated birds to non-vaccinated control birds suggests that aMPV-specific effects as well as adjuvant effects mediated by MP may have contributed to the overall protective effect.

Recent trends in challenges and opportunities of Transdermal drug delivery system

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P.M.Patil; P.D.Chaudhari; Jalpa K.Patel; K.A.Kedar; P.P.Katolkar

2012-01-01

Drug delivery system relates to the production of a drug, its delivery medium, and the way of administration. Drug delivery systems are even used for administering nitroglycerin. Transdermal drug delivery system is the system in which the delivery of the active ingredients of the drug occurs by the means of skin. Various types of transdermal patches are used. There are various methods to enhance the transdermal drug delivery system. But using microfabricated microneedles drugs are delivered v...

Exploitation of sub-micron cavitation nuclei to enhance ultrasound-mediated transdermal transport and penetration of vaccines.

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Bhatnagar, Sunali; Kwan, James J; Shah, Apurva R; Coussios, Constantin-C; Carlisle, Robert C

2016-09-28

Inertial cavitation mediated by ultrasound has been previously shown to enable skin permeabilisation for transdermal drug and vaccine delivery, by sequentially applying the ultrasound then the therapeutic in liquid form on the skin surface. Using a novel hydrogel dosage form, we demonstrate that the use of sub-micron gas-stabilising polymeric nanoparticles (nanocups) to sustain and promote cavitation activity during simultaneous application of both drug and vaccine results in a significant enhancement of both the dose and penetration of a model vaccine, Ovalbumin (OVA), to depths of 500μm into porcine skin. The nanocups themselves exceeded the penetration depth of the vaccine (up to 700μm) due to their small size and capacity to 'self-propel'. In vivo murine studies indicated that nanocup-assisted ultrasound transdermal vaccination achieved significantly (pultrasound-assisted vaccine delivery in the presence of nanocups demonstrated substantially higher specific anti-OVA IgG antibody levels compared to other transdermal methods. Further optimisation can lead to a viable, safe and non-invasive delivery platform for vaccines with potential use in a primary care setting or personalized self-vaccination at home. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Access and Attitudes to HPV Vaccination amongst Hard-To-Reach Populations in Kenya.

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Deborah Watson-Jones

Full Text Available Sub-Saharan Africa bears the greatest burden of cervical cancer. Human papillomavirus (HPV vaccination programmes to prevent the disease will need to reach vulnerable girls who may not be able access health and screening services in the future. We conducted formative research on facilitators and barriers to HPV vaccination and potential acceptability of a future HPV vaccination programme amongst girls living in hard-to-reach populations in Kenya.Stakeholder interviews with Ministry of Health staff explored barriers to and support for the uptake of HPV vaccination. A situation assessment was conducted to assess community services in Maasai nomadic pastoralist communities in Kajiado County and in Korogocho informal settlement in Nairobi city, followed by focus group discussions (n=14 and semi-structured interviews (n=28 with health workers, parents, youth, and community and religious leaders. These covered marriage, knowledge of cervical cancer and HPV, factors that might inhibit or support HPV vaccine uptake and intention to accept HPV vaccine if a programme was in place.Reported challenges to an HPV vaccination programme included school absenteeism and drop-out, early age of sex and marriage, lack of parental support, population mobility and distance from services. Despite little prior knowledge of cervical cancer and HPV, communities were interested in receiving HPV vaccination. Adequate social mobilisation and school-based vaccination, supplemented by out-reach activities, were considered important facilitating factors to achieve high coverage. There was some support for a campaign approach to vaccine delivery.Given the high level of support for a vaccine against cervical cancer and the experience of reaching pastoralist and slum-dwellers for other immunizations, implementing an HPV vaccine programme should be feasible in such hard-to-reach communities. This may require additional delivery strategies in addition to the standard school

Role of the private sector in vaccination service delivery in India: evidence from private-sector vaccine sales data, 2009-12.

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Sharma, Abhishek; Kaplan, Warren A; Chokshi, Maulik; Zodpey, Sanjay P

2016-09-01

India's Universal Immunization Programme (UIP) provides basic vaccines free-of-cost in the public sector, yet national vaccination coverage is poor. The Government of India has urged an expanded role for the private sector to help achieve universal immunization coverage. We conducted a state-by-state analysis of the role of the private sector in vaccinating Indian children against each of the six primary childhood diseases covered under India's UIP. We analyzed IMS Health data on Indian private-sector vaccine sales, 2011 Indian Census data and national household surveys (DHS/NFHS 2005-06 and UNICEF CES 2009) to estimate the percentage of vaccinated children among the 2009-12 birth cohort who received a given vaccine in the private sector in 16 Indian states. We also analyzed the estimated private-sector vaccine shares as function of state-specific socio-economic status. Overall in 16 states, the private sector contributed 4.7% towards tuberculosis (Bacillus Calmette-Guérin (BCG)), 3.5% towards measles, 2.3% towards diphtheria-pertussis-tetanus (DPT3) and 7.6% towards polio (OPV3) overall (both public and private sectors) vaccination coverage. Certain low income states (Uttar Pradesh, Rajasthan, Madhya Pradesh, Orissa, Assam and Bihar) have low private as well as public sector vaccination coverage. The private sector's role has been limited primarily to the high income states as opposed to these low income states where the majority of Indian children live. Urban areas with good access to the private sector and the ability to pay increases the Indian population's willingness to access private-sector vaccination services. In India, the public sector offers vaccination services to the majority of the population but the private sector should not be neglected as it could potentially improve overall vaccination coverage. The government could train and incentivize a wider range of private-sector health professionals to help deliver the vaccines, especially in the low

Identification of protective antigens for vaccination against systemic salmonellosis

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Dirk eBumann

2014-08-01

Full Text Available There is an urgent medical need for improved vaccines with broad serovar coverage and high efficacy against systemic salmonellosis. Subunit vaccines offer excellent safety profiles but require identification of protective antigens, which remains a challenging task. Here, I review crucial properties of Salmonella antigens that might help to narrow down the number of potential candidates from more than 4000 proteins encoded in Salmonella genomes, to a more manageable number of 50-200 most promising antigens. I also discuss complementary approaches for antigen identification and potential limitations of current pre-clinical vaccine testing.

A review of integrating electroactive polymers as responsive systems for specialized drug delivery applications.

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Pillay, Viness; Tsai, Tong-Sheng; Choonara, Yahya E; du Toit, Lisa C; Kumar, Pradeep; Modi, Girish; Naidoo, Dinesh; Tomar, Lomas K; Tyagi, Charu; Ndesendo, Valence M K

2014-06-01

Electroactive polymers (EAPs) are promising candidate materials for the design of drug delivery technologies, especially in conditions where an "on-off" drug release mechanism is required. To achieve this, EAPs such as polyaniline, polypyrrole, polythiophene, ethylene vinyl acetate, and polyethylene may be blended into responsive hydrogels in conjunction with the desired drug to obtain a patient-controlled drug release system. The "on-off" drug release mechanism can be achieved through the environmental-responsive nature of the interpenetrating hydrogel-EAP complex via (i) charged ions initiated diffusion of drug molecules; (ii) conformational changes that occur during redox switching of EAPs; or (iii) electroerosion. These release mechanisms are not exhaustive and new release mechanisms are still under investigation. Therefore, this review seeks to provide a concise incursion and critical overview of EAPs and responsive hydrogels as a strategy for advanced drug delivery, for example, controlled release of neurotransmitters, sulfosalicyclic acid from cross-linked hydrogel, and vaccine delivery. The review further discusses techniques such as linear sweep voltammetry, cyclic voltammetry, impedance spectroscopy, and chronoamperometry for the determination of the redox capability of EAPs. The future implications of the hydrogel-EAP composites include, but not limited to, application toward biosensors, DNA hybridizations, microsurgical tools, and miniature bioreactors and may be utilized to their full potential in the form of injectable devices as nanorobots or nanobiosensors. Copyright © 2013 Wiley Periodicals, Inc.

[Is it ethically acceptable to invite a pregnant woman to enroll in a clinical trial with Tdap if it could entail not being vaccinated with Tdap before delivery?

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Dal-Ré, Rafael

2017-02-01

Pertussis incidence has increased in recent years, especially among infants aged <2months. A number of Spanish regions have started a vaccination program with Tdap vaccine to all pregnant women in the third trimester of pregnancy. An observational study has shown that this strategy reduces the number of cases of pertussis by 90% in infants aged <2months. Mathematical models showed that a cocooning strategy (i.e. vaccination of the mother at immediate postpartum, and other adults and adolescents who have close contact with the newborn and caregivers) will reduce the incidence of pertussis by 70% in infants aged <2months. It is intended to conduct a clinical trial in which 340 pregnant women will receive Tdap vaccine, whereas another 340 pregnant woman will be vaccinated soon after delivery. Vaccination with Tdap will be offered to all partners and caregivers of the newborn. After assessing both the ethical and scientific reasons supporting the trial, it is concluded that it is ethically and legally acceptable to invite pregnant women living in communities where Tdap vaccination has been implemented to participate in the trial. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Two doses of bovine viral diarrhea virus DNA vaccine delivered by electroporation induce long-term protective immune responses.

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van Drunen Littel-van den Hurk, Sylvia; Lawman, Zoe; Snider, Marlene; Wilson, Don; van den Hurk, Jan V; Ellefsen, Barry; Hannaman, Drew

2013-02-01

Bovine viral diarrhea virus (BVDV) is a pathogen of major importance in cattle, so there is a need for new effective vaccines. DNA vaccines induce balanced immune responses and are relatively inexpensive and thus promising for both human and veterinary applications. In this study, newborn calves with maternal antibodies were vaccinated intramuscularly (i.m.) with a BVDV E2 DNA vaccine with the TriGrid Delivery System for i.m. delivery (TDS-IM). Two doses of this vaccine spaced 6 or 12 weeks apart were sufficient to induce significant virus-neutralizing antibody titers, numbers of activated T cells, and reduction in viral shedding and clinical presentations after BVDV-2 challenge. In contrast to the placebo-treated animals, the vaccinated calves did not lose any weight, which is an excellent indicator of the well-being of an animal and has a significant economic impact. Furthermore, the interval between the two vaccinations did not influence the magnitude of the immune responses or degree of clinical protection, and a third immunization was not necessary or beneficial. Since electroporation may enhance not only the magnitude but also the duration of immunity after DNA immunization, the interval between vaccination and challenge was extended in a second trial, which showed that two doses of this E2 DNA vaccine again significantly reduced clinical disease against BVDV for several months. These results are promising and support this technology for use against infectious diseases in cattle and large species, including humans, in general.

Advances in our understanding of immunization and vaccines for patients with systemic lupus erythematosus.