scholarly journals KSAC, the First Defined Polyprotein Vaccine Candidate for Visceral Leishmaniasis

2011 ◽  
Vol 18 (7) ◽  
pp. 1118-1124 ◽  
Author(s):  
Yasuyuki Goto ◽  
Ajay Bhatia ◽  
Vanitha S. Raman ◽  
Hong Liang ◽  
Raodoh Mohamath ◽  
...  
Keyword(s):  
Visceral Leishmaniasis ◽  
Lipid A ◽  
Vaccine Candidate ◽  
Cost Effective ◽  
Content Type ◽  
Monophosphoryl Lipid A ◽  
Multiple Antigen ◽  
Antigen Vaccine ◽  
The Cost ◽  
Multiple Antigen Vaccine

ABSTRACTA subunit vaccine using a defined antigen(s) may be one effective solution for controlling leishmaniasis. Because of genetic diversity in target populations, including both dogs and humans, a multiple-antigen vaccine will likely be essential. However, the cost of a vaccine to be used in developing countries must be considered. We describe herein a multiantigen vaccine candidate comprised of antigens known to be protective in animal models, including dogs, and to be recognized by humans immune to visceral leishmaniasis. The polyprotein (KSAC) formulated with monophosphoryl lipid A, a widely used adjuvant in human vaccines, was found to be immunogenic and capable of inducing protection againstLeishmania infantum, responsible for human and canine visceral leishmaniasis, and againstL. major, responsible for cutaneous leishmaniasis. The results demonstrate the feasibility of producing a practical, cost-effective leishmaniasis vaccine capable of protecting both humans and dogs against multipleLeishmaniaspecies.

The cost-effectiveness of insulin analogs and regular insulin for diabetes control: a case study in Iran

2020 ◽  
Vol 33 (4/5) ◽  
pp. 323-331
Author(s):  
Mohsen pakdaman ◽  
Raheleh akbari ◽  
Hamid reza Dehghan ◽  
Asra Asgharzadeh ◽  
Mahdieh Namayandeh
Keyword(s):  
Cost Effectiveness ◽  
Cost Effective ◽  
Regular Insulin ◽  
Diabetes Control ◽  
Diabetic Patients ◽  
Insulin Analogs ◽  
Content Type ◽  
Patients With Diabetes ◽  
The Government ◽  
The Cost

PurposeFor years, traditional techniques have been used for diabetes treatment. There are two major types of insulin: insulin analogs and regular insulin. Insulin analogs are similar to regular insulin and lead to changes in pharmacokinetic and pharmacodynamic properties. The purpose of the present research was to determine the cost-effectiveness of insulin analogs versus regular insulin for diabetes control in Yazd Diabetes Center in 2017.Design/methodology/approachIn this descriptive–analytical research, the cost-effectiveness index was used to compare insulin analogs and regular insulin (pen/vial) for treatment of diabetes. Data were analyzed in the TreeAge Software and a decision tree was constructed. A 10% discount rate was used for ICER sensitivity analysis. Cost-effectiveness was examined from a provider's perspective.FindingsQALY was calculated to be 0.2 for diabetic patients using insulin analogs and 0.05 for those using regular insulin. The average cost was $3.228 for analog users and $1.826 for regular insulin users. An ICER of $0.093506/QALY was obtained. The present findings suggest that insulin analogs are more cost-effective than regular insulin.Originality/valueThis study was conducted using a cost-effectiveness analysis to evaluate insulin analogs versus regular insulin in controlling diabetes. The results of study are helpful to the government to allocate more resources to apply the cost-effective method of the treatment and to protect patients with diabetes from the high cost of treatment.

The cost competitiveness, competitiveness and sustainability of the hospitality industry in India

2016 ◽  
Vol 8 (4) ◽  
pp. 432-443 ◽  
Author(s):  
Madhu Vij
Keyword(s):  
Hospitality Industry ◽  
Cost Optimization ◽  
Cost Effective ◽  
Comprehensive Treatment ◽  
Global Level ◽  
Content Type ◽  
Present Context ◽  
Cost Competitiveness ◽  
Internal Operations ◽  
The Cost

Purpose This study aims to provide a comprehensive treatment of the various issues surrounding the concept of the cost competitiveness, competitiveness and sustainability of the hospitality industry. We also investigate how innovations in the Indian hospitality industry can optimize costs without compromising the quality of the product or the services offered. Design/methodology/approach The methodology used is mainly survey-based with the use of both structured and unstructured questionnaires. In addition, some interviews were conducted with policy-makers and academics to explore from their perspectives what might be the innovations and sustainability issues in the next decade. Findings The paper helps to identify the essential aspects of cost competitiveness, competitiveness and sustainability in the hospitality industry and to better understand if cost optimization can be accomplished simply by realigning process or cost. These issues have become very important in India in the present context of globalization. Practical implications With growing competition on a global level, the hospitality industry needs to proactively manage its internal operations and focus on reducing costs and raising service quality. In this context, the paper helps to reveal sustainable cost effective practices that are geared to today’s competitive environment. Originality/value The inspiration to write this paper arises from the recent global economic slowdown and the fact that the hospitality industry is confronted with growing competition on a global level. This study highlights how value can be created for customers by applying suitable strategies.

scholarly journals Passive Immunization with a Polyclonal Antiserum to the Hemoglobin Receptor of Haemophilus ducreyi Confers Protection against a Homologous Challenge in the Experimental Swine Model of Chancroid

2011 ◽  
Vol 79 (8) ◽  
pp. 3168-3177 ◽  
Author(s):  
Isabelle Leduc ◽  
William G. Fusco ◽  
Neelima Choudhary ◽  
Patty A. Routh ◽  
Deborah M. Cholon ◽  
...  
Keyword(s):  
Lipid A ◽  
Polyclonal Antibodies ◽  
Passive Immunization ◽  
Etiologic Agent ◽  
Polyclonal Antiserum ◽  
Haemophilus Ducreyi ◽  
Human Model ◽  
Swine Model ◽  
Content Type ◽  
Monophosphoryl Lipid A

ABSTRACTHaemophilus ducreyi, the etiologic agent of chancroid, has an obligate requirement for heme. Heme is acquired byH. ducreyifrom its human host via TonB-dependent transporters expressed at its bacterial surface. Of 3 TonB-dependent transporters encoded in the genome ofH. ducreyi, only the hemoglobin receptor, HgbA, is required to establish infection during the early stages of the experimental human model of chancroid. Active immunization with a native preparation of HgbA (nHgbA) confers complete protection in the experimental swine model of chancroid, using either Freund's or monophosphoryl lipid A as adjuvants. To determine if transfer of anti-nHgbA serum is sufficient to confer protection, a passive immunization experiment using pooled nHgbA antiserum was conducted in the experimental swine model of chancroid. Pigs receiving this pooled nHgbA antiserum were protected from a homologous, but not a heterologous, challenge. Passively transferred polyclonal antibodies elicited to nHgbA bound the surface ofH. ducreyiand partially blocked hemoglobin binding by nHgbA, but were not bactericidal. Taken together, these data suggest that the humoral immune response to the HgbA vaccine is protective against anH. ducreyiinfection, possibly by preventing acquisition of the essential nutrient heme.

scholarly journals The Combinations Chitosan-Pam3CSK4 and Chitosan-Monophosphoryl Lipid A: Promising Immune-Enhancing Adjuvants for Anticaries Vaccine PAc

2019 ◽  
Vol 87 (12) ◽  
Author(s):  
Yongli Bi ◽  
Qingan Xu ◽  
Lingkai Su ◽  
Jiantao Xu ◽  
Zhongfang Liu ◽  
...  
Keyword(s):  
Lipid A ◽  
Vaccine Development ◽  
Protection Effect ◽  
Content Type ◽  
Monophosphoryl Lipid A ◽  
Monophosphoryl Lipid ◽  
Tooth Surfaces ◽  
Antibody Titers

ABSTRACT We previously demonstrated that recombinant protein PAc could be administered as an anticaries vaccine. However, the relatively weak immunogenicity of PAc limits its application. In the present study, we investigated the effect of two adjuvant combinations of chitosan plus Pam3CSK4 (chitosan-Pam3CSK4) and of chitosan plus monophosphoryl lipid A (chitosan-MPL) in the immune responses to the PAc protein in vivo and in vitro. PAc-chitosan-Pam3CSK4 or PAc-chitosan-MPL promoted significantly higher PAc-specific antibody titers in serum and saliva, inhibited Streptococcus mutans colonization onto the tooth surfaces, and endowed better protection effect with significantly less caries activities than PAc alone. Chitosan-Pam3CSK4 and chitosan-MPL showed no statistically significant differences. In conclusion, our study demonstrated that the chitosan-Pam3CSK4 and chitosan-MPL combinations are promising for anticaries vaccine development.

scholarly journals Combining Monophosphoryl Lipid A (MPL), CpG Oligodeoxynucleotide (ODN), and QS-21 Adjuvants Induces Strong and Persistent Functional Antibodies and T Cell Responses against Cell-Traversal Protein for Ookinetes and Sporozoites (CelTOS) ofPlasmodium falciparumin BALB/c Mice

2019 ◽  
Vol 87 (6) ◽  
Author(s):  
Sakineh Pirahmadi ◽  
Sedigheh Zakeri ◽  
Akram A. Mehrizi ◽  
Navid D. Djadid ◽  
Abbas-Ali Raz ◽  
...  
Keyword(s):  
Lipid A ◽  
Enzyme Linked Immunosorbent Assay ◽  
Vaccine Adjuvants ◽  
Content Type ◽  
Quillaja Saponaria ◽  
Monophosphoryl Lipid A ◽  
Monophosphoryl Lipid ◽  
Cpg Oligodeoxynucleotide ◽  
Membrane Feeding ◽  
Functional Antibodies

ABSTRACTPlasmodium falciparumcell-traversal protein for ookinetes and sporozoites (PfCelTOS) is an advanced vaccine candidate that has a crucial role in the traversal of the malaria parasite in both mosquito and mammalian hosts. As recombinant purified proteins are normally poor immunogens, they require to be admixed with an adjuvant(s); therefore, the objective of the present study was to evaluate the capacity of different vaccine adjuvants, monophosphoryl lipid A (MPL), CpG, andQuillaja saponariaMolina fraction 21 (QS-21), alone or in combination (MCQ [MPL/CpG/QS-21]), to enhance the immunogenicity ofEscherichia coli-expressed PfCelTOS in BALB/c mice. This goal was achieved by the assessment of anti-PfCelTOS IgG antibodies (level, titer, IgG isotype profile, avidity, and persistence) and extracellular Th1 cytokines using an enzyme-linked immunosorbent assay (ELISA) on postimmunized BALB/c mouse sera and PfCelTOS-stimulated splenocytes, respectively. Also, an assessment of the transmission-reducing activity (TRA) of anti-PfCelTOS obtained from different vaccine groups was carried out in femaleAnopheles stephensimosquitoes by using a standard membrane feeding assay (SMFA). In comparison to PfCelTOS alone, administration of PfCelTOS with three distinct potent Th1 adjuvants in vaccine mouse groups showed enhancement and improvement of PfCelTOS immunogenicity that generated more bias toward a Th1 response with significantly enhanced titers and avidity of the anti-PfCelTOS responses that could impair ookinete development inA. stephensi. However, immunization of mice with PfCelTOS with MCQ mixture adjuvants resulted in the highest levels of induction of antibody titers, avidity, and inhibitory antibodies in oocyst development (88%/26.7% reductions in intensity/prevalence) inA. stephensi. It could be suggested that adjuvant combinations with different mechanisms stimulate better functional antibody responses than adjuvants individually against challenging diseases such as malaria.

scholarly journals Induction of Protective Antiplague Immune Responses by Self-Adjuvanting Bionanoparticles Derived from Engineered Yersinia pestis

2020 ◽  
Vol 88 (5) ◽  
Author(s):  
Xiuran Wang ◽  
Amit K. Singh ◽  
Xiangmin Zhang ◽  
Wei Sun
Keyword(s):  
Immune Responses ◽  
Yersinia Pestis ◽  
Rational Design ◽  
Lipid A ◽  
Vaccine Development ◽  
Lethal Dose ◽  
Outer Membrane Vesicles ◽  
Vector System ◽  
Content Type ◽  
Monophosphoryl Lipid A

ABSTRACT A Yersinia pestis mutant synthesizing an adjuvant form of lipid A (monophosphoryl lipid A, MPLA) displayed increased biogenesis of bacterial outer membrane vesicles (OMVs). To enhance the immunogenicity of the OMVs, we constructed an Asd-based balanced-lethal host-vector system that oversynthesized the LcrV antigen of Y. pestis, raised the amounts of LcrV enclosed in OMVs by the type II secretion system, and eliminated harmful factors like plasminogen activator (Pla) and murine toxin from the OMVs. Vaccination with OMVs containing MPLA and increased amounts of LcrV with diminished toxicity afforded complete protection in mice against subcutaneous challenge with 8 × 105 CFU (80,000 50% lethal dose [LD50]) and intranasal challenge with 5 × 103 CFU (50 LD50) of virulent Y. pestis. This protection was significantly superior to that resulting from vaccination with LcrV/alhydrogel or rF1-V/alhydrogel. At week 4 postimmunization, the OMV-immunized mice showed more robust titers of antibodies against LcrV, Y. pestis whole-cell lysate (YPL), and F1 antigen and more balanced IgG1:IgG2a/IgG2b-derived Th1 and Th2 responses than LcrV-immunized mice. Moreover, potent adaptive and innate immune responses were stimulated in the OMV-immunized mice. Our findings demonstrate that self-adjuvanting Y. pestis OMVs provide a novel plague vaccine candidate and that the rational design of OMVs could serve as a robust approach for vaccine development.

scholarly journals Monophosphoryl Lipid A Enhances Efficacy of a Francisella tularensis LVS-Catanionic Nanoparticle Subunit Vaccine against F. tularensis Schu S4 Challenge by Augmenting both Humoral and Cellular Immunity

2017 ◽  
Vol 24 (3) ◽  
Author(s):  
Katharina Richard ◽  
Barbara J. Mann ◽  
Aiping Qin ◽  
Eileen M. Barry ◽  
Robert K. Ernst ◽  
...  
Keyword(s):  
Francisella Tularensis ◽  
Subunit Vaccine ◽  
Lipid A ◽  
Ex Vivo ◽  
The United States ◽  
Content Type ◽  
Monophosphoryl Lipid A ◽  
Monophosphoryl Lipid ◽  
Ifn Γ ◽  
Schu S4

ABSTRACT Francisella tularensis, a bacterial biothreat agent, has no approved vaccine in the United States. Previously, we showed that incorporating lysates from partially attenuated F. tularensis LVS or fully virulent F. tularensis Schu S4 strains into catanionic surfactant vesicle (V) nanoparticles (LVS-V and Schu S4-V, respectively) protected fully against F. tularensis LVS intraperitoneal (i.p.) challenge in mice. However, we achieved only partial protection against F. tularensis Schu S4 intranasal (i.n.) challenge, even when employing heterologous prime-boost immunization strategies. We now extend these findings to show that both LVS-V and Schu S4-V immunization (i.p./i.p.) elicited similarly high titers of anti-F. tularensis IgG and that the titers could be further increased by adding monophosphoryl lipid A (MPL), a nontoxic Toll-like receptor 4 (TLR4) adjuvant that is included in several U.S. FDA-approved vaccines. LVS-V+MPL immune sera also detected more F. tularensis antigens than LVS-V immune sera and, after passive transfer to naive mice, significantly delayed the time to death against F. tularensis Schu S4 subcutaneous (s.c.) but not i.n. challenge. Active immunization with LVS-V+MPL (i.p./i.p.) also increased the frequency of gamma interferon (IFN-γ)-secreting activated helper T cells, IFN-γ production, and the ability of splenocytes to control intramacrophage F. tularensis LVS replication ex vivo. Active LVS-V+MPL immunization via heterologous routes (i.p./i.n.) significantly elevated IgA and IgG levels in bronchoalveolar lavage fluid and significantly enhanced protection against i.n. F. tularensis Schu S4 challenge (to ∼60%). These data represent a significant step in the development of a subunit vaccine against the highly virulent type A strains.

Effects of determinants of dried fruit purchase intention and the related consumer segmentation on e-commerce in China

2020 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Yuting Sun ◽  
Chaoyun Liang
Keyword(s):  
Purchase Intention ◽  
Online Survey ◽  
Cost Effective ◽  
Marketing Strategies ◽  
Self Control ◽  
Added Value ◽  
Content Type ◽  
Dried Fruits ◽  
Dried Fruit ◽  
The Cost

PurposeIn this study, a comprehensive theoretical framework was developed to investigate the influence of the determinants of online dried fruit purchase intention in China.Design/methodology/approachThe dried fruit eating experiences of 1,160 participants from China were collected using an online survey.FindingsSignificant differences were noted in the sociodemographic distributions among three age-based consumer segments. Furthermore, the cost of the marketing strategy had the strongest effect on online dried fruit purchase intention. Finally, different patterns of online dried fruit purchase intention were observed among the three consumer segments: consumers aged below 24 years regarded dried fruits as a new and healthy snack choice and favoured companies with high-quality communication with consumers; consumers aged 25–29 years viewed dried fruits as a healthy eating habit, reflecting their strong self-control over their lifestyle; and consumers aged over 30 years valued the convenience marketing strategies applied by dried fruit manufacturers.Originality/valueOverall, the results indicate that dried fruits are considered a niche market of snacks that provides added value for core products in the Chinese e-commerce (EC) market; therefore, developing cost-effective strategies to raise consumer awareness of dried fruits is crucial. Furthermore, marketing strategies should target different consumer segments.

Preparing a framework for two-stage target-cost arrangement formulation

2016 ◽  
Vol 9 (1) ◽  
pp. 123-146 ◽  
Author(s):  
Pertti Lahdenperä
Keyword(s):  
Service Provider ◽  
Development Process ◽  
Cost Effective ◽  
Two Stage ◽  
Content Type ◽  
Investment Projects ◽  
Second Stage ◽  
Target Cost ◽  
The Cost ◽  
Concrete Model

Purpose – Early involvement of the project team with the construction resources seems to be gaining popularity as it aims to improve the cost efficiency of a project as there is significantly more potential to influence the project solution at that point in time. The missing price during early involvement/selection and the principal-agent setting, however, tend to leave the project owner in doubt of the reasonableness of pricing when it is fixed only later after the joint design phase involving the service provider and the owner. The purpose of this paper is to find a solution for this challenge. Design/methodology/approach – A two-stage target-cost (2STC) arrangement has been proposed as the solution. In this model the service provider earns a bonus by suggesting a lower target cost than the reference set at the time of the involvement of the provider. The amount of bonus also impacts the cost over-run risk transferred to the service provider to avoid overly optimistic promises. The proposition encompassed just the basic idea, and did not really delve into actual model formulations and their functioning under practical realities. Therefore, the required work is presented here in the form of a conceptual, discursive study focusing on relevant theories and empirical findings from major investment projects. Findings – The study produces a requirement framework for the 2STC model to allow functioning models to be formulated and tested. The framework incorporates numerous requirements, constraints and a suggested path forward. For instance, while the model may not be manipulatable, it must incentivise the service provider to seek more cost-effective project solutions, be feasible also from the view of the project owner and adapt to various project risk profiles and ranges of efficiency improvements. Research limitations/implications – The study suggests more concrete model formulations to be provided under the guidance of the presented framework. Originality/value – The 2STC model is a unique concept and no comparable construct is known to exist. Besides the requirement framework, the study also strengthens the foundation of and need for the 2STC model by a thorough survey of its theoretical linkages. Accordingly, the study presented in this paper forms the second stage in the overall 2STC development process focused on benefiting project owners and the industry.

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