Hofman, R.; Empelen, P. van; Vogel, I.; Raat, H.; Ballegooijen, M. van; Korfage, I.J.
Before the introduction of the human papillomavirus (HPV) vaccine, decisional strategies and factors that could guide HPV vaccination intentions were explored. The authors conducted 4 focus group discussions with 36 parents of children 8-15 years of age. Three groups consisted primarily of Dutch
Nabel, Gary J
Traditional methods of vaccine development have not produced effective vaccines for several prevalent infectious diseases, including AIDS, malaria and tuberculosis. These difficult diseases call attention to the importance of new approaches that profit from modern technologies. Successful efforts in the past have typically taken advantage of naturally occurring, protective immune responses, but this avenue is not readily available in certain cases, such as in HIV infection, where the immune system rarely confers protective immunity. However, there are alternative strategies and areas of research that may facilitate the development of highly effective vaccines. These include the identification of immunogens that elicit broadly neutralizing antibodies, determination of the molecular and cellular basis for immune responses to the components of the infectious agent, the identification of relevant forms of viral proteins for antigen presentation, stimulation of relevant T-cell types, and enhancement of antigen-presenting, dendritic cell function. Answering these basic research questions will aid in rational vaccine design. It is also extremely important to optimize techniques for the testing and production of new vaccines including the quantitation of immune responses in animals and in humans, identification of surrogate markers of immune protection, streamlined vaccine production, and rapid evaluation of candidate vaccines for testing in clinical trials. We have put these ideas into practice in two recent studies in which we generated enhanced cytotoxic T lymphocyte (CTL) responses, while retaining robust humoral responses, to wild-type viral proteins by immunizing mice with genetically modified forms of HIV-1 Env, Gag and Pol delivered in the form of plasmid DNA expression vectors.
Correia, Bruno E.; Bates, John T.; Loomis, Rebecca J.; Baneyx, Gretchen; Carrico, Chris; Jardine, Joseph G.; Rupert, Peter; Correnti, Colin; Kalyuzhniy, Oleksandr; Vittal, Vinayak; Connell, Mary J.; Stevens, Eric; Schroeter, Alexandria; Chen, Man; MacPherson, Skye; Serra, Andreia M.; Adachi, Yumiko; Holmes, Margaret A.; Li, Yuxing; Klevit, Rachel E.; Graham, Barney S.; Wyatt, Richard T.; Baker, David; Strong, Roland K.; Crowe, James E.; Johnson, Philip R.; Schief, William R.
Vaccines prevent infectious disease largely by inducing protective neutralizing antibodies against vulnerable epitopes. Several major pathogens have resisted traditional vaccine development, although vulnerable epitopes targeted by neutralizing antibodies have been identified for several such cases. Hence, new vaccine design methods to induce epitope-specific neutralizing antibodies are needed. Here we show, with a neutralization epitope from respiratory syncytial virus, that computational protein design can generate small, thermally and conformationally stable protein scaffolds that accurately mimic the viral epitope structure and induce potent neutralizing antibodies. These scaffolds represent promising leads for the research and development of a human respiratory syncytial virus vaccine needed to protect infants, young children and the elderly. More generally, the results provide proof of principle for epitope-focused and scaffold-based vaccine design, and encourage the evaluation and further development of these strategies for a variety of other vaccine targets, including antigenically highly variable pathogens such as human immunodeficiency virus and influenza.
Riese, Peggy; Sakthivel, Priya; Trittel, Stephanie; Guzmán, Carlos A
The emergence of new diseases and the lack of efficient vaccines against numerous non-treatable pathogens require the development of novel vaccination strategies. To date, only a few mucosal vaccines have been approved for humans. This was in part due to i) the use of live attenuated vaccines, which are not suitable for certain groups of individuals, ii) safety concerns derived from implementation in humans of some mucosal vaccines, iii) the poor stability, absorption and immunogenicity of antigens delivered by the mucosal route and iv) the limited number of available technologies to overcome the bottlenecks associated with mucosal antigen delivery. Recent advances make feasible the development of efficacious mucosal vaccines with adequate safety profile. Thus, currently intranasal vaccines represent an attractive and valid alternative to conventional vaccines. The present review is focused on the potentials and limitations of market-approved intranasal vaccines and promising candidates undergoing clinical investigations. Furthermore, emerging strategies to overcome main bottlenecks including efficient breaching of the mucosal barrier and safety concerns by implementation of new adjuvants and delivery systems are discussed. The rational design of intranasal vaccines requires an in-depth understanding of the anatomic, physicochemical and barrier properties of the nasal mucosa, as well as the molecular mechanisms governing the activation of the local innate and adaptive immune system. This would provide the critical knowledge to establish effective approaches to deliver vaccine antigens across the mucosal barrier, supporting the stimulation of a long-lasting protective response at both mucosal and systemic levels. Current developments in the area of adjuvants, nanotechnologies and mucosal immunology, together with the identification of surface receptors that can be exploited for cell targeting and manipulating their physiological properties, will become instrumental
Nascimento, I.P.; Leite, L.C.C. [Centro de Biotecnologia, Instituto Butantan, São Paulo, SP (Brazil)
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.
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.
Full Text Available In this review the authors analyze the effector and regulatory mechanisms in the immune response to schistosomiasis. To study these mechanisms two animal models were used, mouse and rat. The mouse totaly permissive host like human, show prominent-T cell control in the acquisition of resistance. But other mechanisms like antibody mediated cytotoxity (ADCC involving eosinophils and IgG antibodies described in humans, are observed in rats. Also in this animal, it is observed specific IgE antibody high production and blood and tisssue eosinophilia. Using the rat model and schistosomula as target, some ADCC features have emerged: the cellular population involved are bone marrow derived inflammatory cell (mononuclear phagocytes, eosinophils and platelets, interacting with IgE through IgE Fc receptors. Immunization has been attempted using the recombinant protein Sm28/GST. Protection has been observed in rodents with significant decrease of parasite fecundity and egg viability affecting the number, size and volume of liver egg granulomas. The association of praziquantel and immunization with with Sm28/GST increases the resistance to infection and decreases egg viability. The authors suggest the possibility of the stablishment of a future vaccine against Schistosoma mansoni.
Paran, Nir; Sutter, Gerd
Smallpox has been eradicated but stockpiles of the causative infectious agent, variola virus, have been maintained over decades. Today, the threat of accidental or intentional poxvirus release is accompanied by the fact that the existing licensed smallpox vaccines cause rare but severe adverse reactions yet are the only products with approved efficacy against smallpox. New safer vaccines and new strategies of immunization are to be developed to fit to a scenario of emergency smallpox vaccination. However, we still lack knowledge about the pathogen and the mechanisms involved in acquiring protective immunity. Here, we review the history of smallpox vaccines and recent achievements in the development of highly efficacious and safer vaccines and vaccine applications. These include i) assessment of adequate animal models to study pathogenesis and protective immunity, ii) characterization of the immunity elicited by next generation vaccines, and (iii) the investigation of the requirements for rapidly protective vaccination.
Bitton, Roberto J; Guthmann, Marcel D; Gabri, Mariano R; Carnero, Ariel J L; Alonso, Daniel F; Fainboim, Leonardo; Gomez, Daniel E
the Inmunologia Molecular> (CIM) from La Havana, Cuba, to developed new strategies for specific active immunotherapy. The project included two ganglioside based vaccines and one anti-idiotypic vaccine. We focused on two antigens: first GM3, an ubiquitous antigen which is over-expressed in several epithelial tumor types; and a second one, N-Glycolyl-GM3 a more molecule, not being expressed in normal tissues and recently found in several neoplastic cells, in particular breast, melanoma and neuroectodermal cancer cells. We developed two vaccines, one with each antigen, both using proteins derived from the outer membrane proteins (OMP) of Neisseria Meningitidis B, as carriers. We developed also the 1E10 vaccine; an anti-idiotype vaccine designed to mimic the N-Glycolyl-GM3 gangliosides. This monoclonal antibody is an Ab2-type-antibody which recognizes the Ab1 antibody called P3, the latter is a monoclonal antibody that specifically recognizes gangliosides as antigens. Since 1998 we initiated a clinical development program for these three compounds. Results of the phase I clinical trials proved that the three vaccines were safe and able to elicit specific antibody responses. In addition we were able to demonstrate the activation of the cellular arm of the immune response in patients treated with the GM3 vaccine. Although phase I trials are not designed to evaluate antitumor efficacy, it was encouraging to observe tumor shrinkage in some patients treated both with the GM3 and N-Glycolyl-GM3 vaccines. We have already begun a phase II program in several neoplastic diseases, with all three vaccines.
de Vries, Rory D; Stittelaar, Koert J; Osterhaus, Albert D M E; de Swart, Rik L
Measles is a highly contagious viral disease. With 1 million deaths reported in 1996, measles was the leading cause of vaccine-preventable deaths. However, in recent years, significant progress has been made in measles control, reducing deaths attributed to measles to 454,000 in 2004 and 242,000 in 2006. The main strategy behind this reduction has been the improvement of vaccination coverage and implementation of a second opportunity for immunization with the live-attenuated measles vaccine. The Measles Initiative, a partnership between the American Red Cross, CDC, UNICEF, WHO and UN Foundation, has had a significant role in this achievement. Here, we provide an overview of old and new vaccination strategies, and discuss changes in the route of administration of the existing live-attenuated vaccine, the development of new-generation nonreplicating measles virus vaccine candidates and attempts to use recombinant measles virus as a vector for vaccination against other pathogens.
Hanslik, Thomas; Boëlle, Pierre Yves
This article summarises the various stages of the risk/benefit assessment of vaccination strategies. Establishing the awaited effectiveness of a vaccination strategy supposes to have an epidemiologic description of the disease to be prevented. The effectiveness of the vaccine strategy will be thus expressed in numbers of cases, hospitalizations or deaths avoided. The effectiveness can be direct, expressed as the reduction of the incidence of the infectious disease in the vaccinated subjects compared to unvaccinated subjects. It can also be indirect, the unvaccinated persons being protected by the suspension in circulation of the pathogenic agent, consecutive to the implementation of the vaccination campaign. The risks of vaccination related to the adverse effects detected during the clinical trials preceding marketing are well quantified, but other risks can occur after marketing: e.g., serious and unexpected adverse effects detected by vaccinovigilance systems, or risk of increase in the age of cases if the vaccination coverage is insufficient. The medico-economic evaluation forms a part of the risks/benefit assessment, by positioning the vaccine strategy comparatively with other interventions for health. Epidemiologic and vaccinovigilance informations must be updated very regularly, which underlines the need for having an operational and reliable real time monitoring system to accompany the vaccination strategies. Lastly, in the context of uncertainty which often accompanies the risks/benefit assessments, it is important that an adapted communication towards the public and the doctors is planned.
Barry, Alyssa E.; Arnott, Alicia
After more than 50 years of intensive research and development, only one malaria vaccine candidate, “RTS,S,” has progressed to Phase 3 clinical trials. Despite only partial efficacy, this candidate is now forecast to become the first licensed malaria vaccine. Hence, more efficacious second-generation malaria vaccines that can significantly reduce transmission are urgently needed. This review will focus on a major obstacle hindering development of effective malaria vaccines: parasite antigenic diversity. Despite extensive genetic diversity in leading candidate antigens, vaccines have been and continue to be formulated using recombinant antigens representing only one or two strains. These vaccine strains represent only a small fraction of the diversity circulating in natural parasite populations, leading to escape of non-vaccine strains and challenging investigators’ abilities to measure strain-specific efficacy in vaccine trials. Novel strategies are needed to overcome antigenic diversity in order for vaccine development to succeed. Many studies have now cataloged the global diversity of leading Plasmodium falciparum and Plasmodium vivax vaccine antigens. In this review, we describe how population genetic approaches can be applied to this rich data source to predict the alleles that best represent antigenic diversity, polymorphisms that contribute to it, and to identify key polymorphisms associated with antigenic escape. We also suggest an approach to summarize the known global diversity of a given antigen to predict antigenic diversity, how to select variants that best represent the strains circulating in natural parasite populations and how to investigate the strain-specific efficacy of vaccine trials. Use of these strategies in the design and monitoring of vaccine trials will not only shed light on the contribution of genetic diversity to the antigenic diversity of malaria, but will also maximize the potential of future malaria vaccine candidates. PMID
Alyssa E Barry
Full Text Available After more than 50 years of intensive research and development, only one malaria vaccine candidate, RTS,S, has progressed to Phase 3 clinical trials. Despite only partial efficacy, this candidate is now forecast to become the first licensed malaria vaccine. Hence, more efficacious second-generation malaria vaccines that can significantly reduce transmission are urgently needed. This review will focus on a major obstacle hindering development of effective malaria vaccines: parasite antigenic diversity. Despite extensive genetic diversity in leading candidate antigens, vaccines have been and continue to be formulated using recombinant antigens representing only one or two strains. These vaccine strains represent only a small fraction of the diversity circulating in natural parasite populations, leading to escape of non-vaccine strains and challenging investigators’ abilities to measure strain-specific efficacy in vaccine trials. Novel strategies are needed to overcome antigenic diversity in order for vaccine development to succeed. Many studies have now catalogued the global diversity of leading Plasmodium falciparum and Plasmodium vivax vaccine antigens. In this review, we describe how population genetic approaches can be applied to this rich data source to predict the alleles that best represent antigenic diversity, polymorphisms that contribute to it, and to identify key polymorphisms associated with antigenic escape. We also suggest an approach to summarise the known global diversity of a given antigen to predict antigenic diversity, how to select variants that best represent the strains circulating in natural parasite populations and how to investigate the strain-specific efficacy of vaccine trials. Use of these strategies in the design and monitoring of vaccine trials will not only shed light on the contribution of genetic diversity to the antigenic diversity of malaria, but will also maximise the potential of future malaria vaccine
Liu, Yang; Liu, Jianying; Cheng, Gong
Dengue is currently the most significant arboviral disease afflicting tropical and sub-tropical countries worldwide. Dengue vaccines, such as the multivalent attenuated, chimeric, DNA and inactivated vaccines, have been developed to prevent dengue infection in humans, and they function predominantly by stimulating immune responses against the dengue virus (DENV) envelope (E) and nonstructural-1 proteins (NS1). Of these vaccines, a live attenuated chimeric tetravalent DENV vaccine developed by Sanofi Pasteur has been licensed in several countries. However, this vaccine renders only partial protection against the DENV2 infection and is associated with an unexplained increased incidence of hospitalization for severe dengue disease among children younger than nine years old. In addition to the virus-based vaccines, several mosquito-based dengue immunization strategies have been developed to interrupt the vector competence and effectively reduce the number of infected mosquito vectors, thus controlling the transmission of DENV in nature. Here we summarize the recent progress in the development of dengue vaccines and novel immunization strategies and propose some prospective vaccine strategies for disease prevention in the future.
van der Laan, Jan Willem; Gould, Sarah; Tanir, Jennifer Y
Questions have been recently raised regarding the safety of vaccine adjuvants, particularly in relation to autoimmunity or autoimmune disease(s)/disorder(s) (AID). The International Life Sciences Institute (ILSI) Health and Environmental Sciences Institute (HESI) formed a scientific committee and convened a 2-day workshop, consisting of technical experts from around the world representing academia, government regulatory agencies, and industry, to investigate and openly discuss the issues around adjuvant safety in vaccines. The types of adjuvants considered included oil-in-water emulsions and toll-like receptor (TLR) agonists. The state of science around the use of animal models and biomarkers for the evaluation and prediction of AID were also discussed. Following extensive literature reviews by the HESI committee, and presentations by experts at the workshop, several key points were identified, including the value of animal models used to study autoimmunity and AID toward studying novel vaccine adjuvants; whether there is scientific evidence indicating an intrinsic risk of autoimmunity and AID with adjuvants, or a higher risk resulting from the mechanism of action; and if there is compelling clinical data linking adjuvants and AID. The tripartite group of experts concluded that there is no compelling evidence supporting the association of vaccine adjuvants with autoimmunity signals. Additionally, it is recommended that future research on the potential effects of vaccine adjuvants on AID should consider carefully the experimental design in animal models particularly if they are to be used in any risk assessment, as an improper design and model could result in misleading information. Finally, studies on the mechanistic aspects and potential biomarkers related to adjuvants and autoimmunity phenomena could be developed. Copyright © 2015. Published by Elsevier Ltd.. All rights reserved.
Munang’andu, Hetron Mweemba; Paul, Joydeb; Evensen, Øystein
Streptococcus agalactiae is an emerging infectious disease adversely affecting Nile tilapia (Niloticus oreochromis) production in aquaculture. Research carried out in the last decade has focused on developing protective vaccines using different strategies, although no review has been carried out to evaluate the efficacy of these strategies. The purpose of this review is to provide a synopsis of vaccination strategies and antigen delivery systems currently used for S. agalactiae vaccines in tilapia. Furthermore, as shown herein, current vaccine designs include the use of replicative antigen delivery systems, such as attenuated virulent strains, heterologous vectors and DNA vaccines, while non-replicative vaccines include the inactivated whole cell (IWC) and subunit vaccines encoding different S. agalactiae immunogenic proteins. Intraperitoneal vaccination is the most widely used immunization strategy, although immersion, spray and oral vaccines have also been tried with variable success. Vaccine efficacy is mostly evaluated by use of the intraperitoneal challenge model aimed at evaluating the relative percent survival (RPS) of vaccinated fish. The major limitation with this approach is that it lacks the ability to elucidate the mechanism of vaccine protection at portals of bacterial entry in mucosal organs and prevention of pathology in target organs. Despite this, indications are that the correlates of vaccine protection can be established based on antibody responses and antigen dose, although these parameters require optimization before they can become an integral part of routine vaccine production. Nevertheless, this review shows that different approaches can be used to produce protective vaccines against S. agalactiae in tilapia although there is a need to optimize the measures of vaccine efficacy. PMID:27983591
Munang'andu, Hetron Mweemba; Paul, Joydeb; Evensen, Øystein
Streptococcus agalactiae is an emerging infectious disease adversely affecting Nile tilapia (Niloticus oreochromis) production in aquaculture. Research carried out in the last decade has focused on developing protective vaccines using different strategies, although no review has been carried out to evaluate the efficacy of these strategies. The purpose of this review is to provide a synopsis of vaccination strategies and antigen delivery systems currently used for S. agalactiae vaccines in tilapia. Furthermore, as shown herein, current vaccine designs include the use of replicative antigen delivery systems, such as attenuated virulent strains, heterologous vectors and DNA vaccines, while non-replicative vaccines include the inactivated whole cell (IWC) and subunit vaccines encoding different S. agalactiae immunogenic proteins. Intraperitoneal vaccination is the most widely used immunization strategy, although immersion, spray and oral vaccines have also been tried with variable success. Vaccine efficacy is mostly evaluated by use of the intraperitoneal challenge model aimed at evaluating the relative percent survival (RPS) of vaccinated fish. The major limitation with this approach is that it lacks the ability to elucidate the mechanism of vaccine protection at portals of bacterial entry in mucosal organs and prevention of pathology in target organs. Despite this, indications are that the correlates of vaccine protection can be established based on antibody responses and antigen dose, although these parameters require optimization before they can become an integral part of routine vaccine production. Nevertheless, this review shows that different approaches can be used to produce protective vaccines against S. agalactiae in tilapia although there is a need to optimize the measures of vaccine efficacy.
Doroud, Delaram; Rafati, Sima
Although mass vaccination of the entire population of an endemic area would be the most cost-effective tool to diminish Leishmania burden, an effective vaccine is not yet commercially available. Practically, vaccines have failed to achieve the required level of protection, possibly owing to the lack of an appropriate adjuvant and/or delivery system. Therefore, there is still an imperative demand for an improved, safe and efficient delivery system to enhance the immunogenicity of available vaccine candidates. Nanoparticles are proficient in boosting the quality and magnitude of immune responses in a predictable fashion. Herein, we discuss how nanoparticulate vaccine delivery systems can be used to induce appropriate immune responses against leishmaniasis by controlling physicochemical properties of the vaccine. Stability, production reproducibility, low cost per dose and low risk-benefit ratios are desirable characteristics of an ideal vaccine formulation and solid lipid nanoparticles may serve as one of the most promising practical strategies to help to achieve such a leishmanial vaccine, at least in canine species in the developing world.
Jarrett, Caitlin; Wilson, Rose; O'Leary, Maureen; Eckersberger, Elisabeth; Larson, Heidi J
The purpose of this systematic review is to identify, describe and assess the potential effectiveness of strategies to respond to issues of vaccine hesitancy that have been implemented and evaluated across diverse global contexts. A systematic review of peer reviewed (January 2007-October 2013) and grey literature (up to October 2013) was conducted using a broad search strategy, built to capture multiple dimensions of public trust, confidence and hesitancy concerning vaccines. This search strategy was applied and adapted across several databases and organizational websites. Descriptive analyses were undertaken for 166 (peer reviewed) and 15 (grey literature) evaluation studies. In addition, the quality of evidence relating to a series of PICO (population, intervention, comparison/control, outcomes) questions defined by the SAGE Working Group on Vaccine Hesitancy (WG) was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria; data were analyzed using Review Manager. Across the literature, few strategies to address vaccine hesitancy were found to have been evaluated for impact on either vaccination uptake and/or changes in knowledge, awareness or attitude (only 14% of peer reviewed and 25% of grey literature). The majority of evaluation studies were based in the Americas and primarily focused on influenza, human papillomavirus (HPV) and childhood vaccines. In low- and middle-income regions, the focus was on diphtheria, tetanus and pertussis, and polio. Across all regions, most interventions were multi-component and the majority of strategies focused on raising knowledge and awareness. Thirteen relevant studies were used for the GRADE assessment that indicated evidence of moderate quality for the use of social mobilization, mass media, communication tool-based training for health-care workers, non-financial incentives and reminder/recall-based interventions. Overall, our results showed that multicomponent and dialogue
Full Text Available Mohan Karkada,1,2 Neil L Berinstein,3 Marc Mansour1 1ImmunoVaccine Inc, 2Department of Microbiology/Immunology, Dalhousie University, Halifax, NS, Canada; 3Ontario Institute for Cancer Research, Toronto, ON, Canada Abstract: In an attempt to significantly enhance immunogenicity of peptide cancer vaccines, we developed a novel non-emulsion depot-forming vaccine platform called DepoVax™ (DPX. Human leukocyte antigen (HLA-A2 restricted peptides naturally presented by cancer cells were used as antigens to create a therapeutic cancer vaccine, DPX-0907. In a phase I clinical study, the safety and immune-activating potential of DPX-0907 in advanced-stage breast, ovarian, and prostate cancer patients were examined, following encouraging results in HLA-A2 transgenic mice. The DPX-0907 vaccine was shown to be safe and well tolerated, with injection-site reactions being the most commonly reported adverse event. Vaccinated cancer patients exhibited a 61% immune response rate, with higher response rates in the breast and ovarian cancer patient cohorts. In keeping with the higher immune efficacy of this vaccine platform, antigen-specific responses were detected in 73% of immune responders after just one vaccination. In 83% of responders, peptide-specific T-cells were detected at two or more time points post-vaccination, with 64% of these patients showing evidence of immune persistence. Immune monitoring also demonstrated the generation of antigen-specific T-cell memory, with the ability to secrete multiple type 1 cytokines. The novel DPX formulation promotes multifunctional effector/memory responses to peptide-based tumor-associated antigens. The data support the capacity of DPX-0907 to elicit type-1 biased immune responses, warranting further clinical development of the vaccine. In this review, we discuss the rationale for developing DPX-based therapeutic cancer vaccine(s, with a focus on DPX-0907, aimed at inducing efficient anti-tumor immunity that may
Yi, Ming; Marathe, Achla
To develop a framework to objectively measure the degree of fairness of any allocation rule aimed at distributing a limited stockpile of vaccines to contain the spread of influenza. The trade-off between the efficiency and fairness of allocation strategies was demonstrated through an illustrative simulation study of an influenza epidemic in Southwestern Virginia. A Susceptible-Exposed-Infectious-Recovered model was used to represent the disease progression within the host. Our findings showed that among all the criteria considered here, the household size (largest first) combined with age (youngest first)-based strategy leads to the best outcome. At 80% fairness, highest efficiency can be achieved but in order to be 100% fair, disease prevalence will have to rise by approximately 1.5%. This research provides a framework to objectively determine the degree of fairness of vaccine allocation strategies. Copyright © 2015 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.
Hofstetter, Annika M; LaRussa, Philip; Rosenthal, Susan L
Adolescents with chronic medical conditions (CMCs), a growing population worldwide, possess a wide array of preventive health care needs. Vaccination is strongly recommended for the vast majority of these adolescents given their increased risk of vaccine preventable infection and associated complications. Not only should they receive routine vaccines, but some also require additional vaccines. Despite these guidelines, evidence suggests that adolescents with CMCs often fail to receive needed vaccines. Many factors contribute to this under-immunization, including lack of knowledge among parents and providers and suboptimal coordination of primary and subspecialty care. This review describes current vaccination recommendations for these adolescents as well as recent data related to infection risk, vaccine efficacy and safety, vaccination coverage, and the unique multilevel factors impacting uptake in this population. It also discusses strategies for improving coverage levels and reducing missed vaccination opportunities, with a particular focus on technology-based interventions. PMID:26212313
Yamamoto, M; Pascual, D W; Kiyono, H
Immune responses in the aerodigestive tract are characterized by production and transport of specific IgA antibodies across the epithelium to act as a first line of defense against pathogens in the external environment. To sample antigens on mucosal surfaces in the intestine and upper respiratory tract, the immune system relies on a close collaboration between specialized antigen-sampling epithelial M cells and lymphoid cells. Depending on various factors, local antigen presentation in the mucosal tissue leads to tolerance or initiation of an active immune response. Recently, molecules that could be used to target vaccine antigens to apical M cell surfaces have been identified. Here we review the M cell-targeted vaccine strategy, an approach that could be used to enhance uptake and efficacy of vaccines delivered in the nasal cavity or intestine.
Bushell, Mary; Morrissey, Hana; Ball, Patrick
Introduction: Focus group methodology is commonly used to quickly collate, integrated views from a variety of different stakeholders. This paper provides an example of how focus groups can be employed to collate expert opinion informing amendments on a newly developed training program for integration into undergraduate pharmacy curricula. Materials and methods: Four focus groups were conducted, across three continents, to determine the appropriateness and reliability of a developed vaccination training program with nested injection skills training. All focus groups were comprised of legitimate experts in the field of vaccination, medicine and/or pharmacy. Results: Themes that emerged across focus groups informed amendments giving rise to a validated version of a training program. Discussion: The rigorous validation of the vaccination training program offers generalizable lessons to inform the design and validation of future training programs intended for the health sector and or pharmacy curricula. Using the knowledge and experience of focus group participants fostered collaborative problem solving and validation of material and concept development. The group dynamics of a focus group allowed synthesis of feedback in an inter-professional manner. Conclusions: This paper provides a demonstration of how focus groups can be structured and used by health researchers to validate a newly developed training program.
Full Text Available Introduction: Focus group methodology is commonly used to quickly collate, integrated views from a variety of different stakeholders. This paper provides an example of how focus groups can be employed to collate expert opinion informing amendments on a newly developed training program for integration into undergraduate pharmacy curricula. Materials and methods: Four focus groups were conducted, across three continents, to determine the appropriateness and reliability of a developed vaccination training program with nested injection skills training. All focus groups were comprised of legitimate experts in the field of vaccination, medicine and/or pharmacy. Results: Themes that emerged across focus groups informed amendments giving rise to a validated version of a training program. Discussion: The rigorous validation of the vaccination training program offers generalizable lessons to inform the design and validation of future training programs intended for the health sector and or pharmacy curricula. Using the knowledge and experience of focus group participants fostered collaborative problem solving and validation of material and concept development. The group dynamics of a focus group allowed synthesis of feedback in an inter-professional manner. Conclusions: This paper provides a demonstration of how focus groups can be structured and used by health researchers to validate a newly developed training program.
Full Text Available Dengue is a highly endemic infectious disease of the tropical countries and is rapidly becoming a global burden. It is caused by any of the 4 serotypes of dengue virus and is transmitted within humans through female Aedes mosquitoes. Dengue disease varies from mild fever to severe conditions of dengue hemorrhagic fever and shock syndrome. Globalization, increased air travel, and unplanned urbanization have led to increase in the rate of infection and helped dengue to expand its geographic and demographic distribution. Dengue vaccine development has been a challenging task due to the existence of four antigenically distinct dengue virus serotypes, each capable of eliciting cross-reactive and disease-enhancing antibody response against the remaining three serotypes. Recently, Sanofi Pasteur’s chimeric live-attenuated dengue vaccine candidate has been approved in Mexico, Brazil, and Philippines for usage in adults between 9 and 45 years of age. The impact of its limited application to the public health system needs to be evaluated. Simultaneously, the restricted application of this vaccine candidate warrants continued efforts in developing a dengue vaccine candidate which is additionally efficacious for infants and naïve individuals. In this context, alternative strategies of developing a designed vaccine candidate which does not allow production of enhancing antibodies should be explored, as it may expand the umbrella of efficacy to include infants and naïve individuals.
Khetarpal, Niyati; Khanna, Ira
Dengue is a highly endemic infectious disease of the tropical countries and is rapidly becoming a global burden. It is caused by any of the 4 serotypes of dengue virus and is transmitted within humans through female Aedes mosquitoes. Dengue disease varies from mild fever to severe conditions of dengue hemorrhagic fever and shock syndrome. Globalization, increased air travel, and unplanned urbanization have led to increase in the rate of infection and helped dengue to expand its geographic and demographic distribution. Dengue vaccine development has been a challenging task due to the existence of four antigenically distinct dengue virus serotypes, each capable of eliciting cross-reactive and disease-enhancing antibody response against the remaining three serotypes. Recently, Sanofi Pasteur's chimeric live-attenuated dengue vaccine candidate has been approved in Mexico, Brazil, and Philippines for usage in adults between 9 and 45 years of age. The impact of its limited application to the public health system needs to be evaluated. Simultaneously, the restricted application of this vaccine candidate warrants continued efforts in developing a dengue vaccine candidate which is additionally efficacious for infants and naïve individuals. In this context, alternative strategies of developing a designed vaccine candidate which does not allow production of enhancing antibodies should be explored, as it may expand the umbrella of efficacy to include infants and naïve individuals.
Dimitrov, Dobromir T.; Troeger, Christopher; Halloran, M. Elizabeth; Longini, Ira M.; Chao, Dennis L.
Background Killed, oral cholera vaccines have proven safe and effective, and several large-scale mass cholera vaccination efforts have demonstrated the feasibility of widespread deployment. This study uses a mathematical model of cholera transmission in Bangladesh to examine the effectiveness of potential vaccination strategies. Methods & Findings We developed an age-structured mathematical model of cholera transmission and calibrated it to reproduce the dynamics of cholera in Matlab, Bangladesh. We used the model to predict the effectiveness of different cholera vaccination strategies over a period of 20 years. We explored vaccination programs that targeted one of three increasingly focused age groups (the entire vaccine-eligible population of age one year and older, children of ages 1 to 14 years, or preschoolers of ages 1 to 4 years) and that could occur either as campaigns recurring every five years or as continuous ongoing vaccination efforts. Our modeling results suggest that vaccinating 70% of the population would avert 90% of cholera cases in the first year but that campaign and continuous vaccination strategies differ in effectiveness over 20 years. Maintaining 70% coverage of the population would be sufficient to prevent sustained transmission of endemic cholera in Matlab, while vaccinating periodically every five years is less effective. Selectively vaccinating children 1–14 years old would prevent the most cholera cases per vaccine administered in both campaign and continuous strategies. Conclusions We conclude that continuous mass vaccination would be more effective against endemic cholera than periodic campaigns. Vaccinating children averts more cases per dose than vaccinating all age groups, although vaccinating only children is unlikely to control endemic cholera in Bangladesh. Careful consideration must be made before generalizing these results to other regions. PMID:25473851
Vernon J Lee
Full Text Available BACKGROUND: All influenza pandemic plans advocate pandemic vaccination. However, few studies have evaluated the cost-effectiveness of different vaccination strategies. This paper compares the economic outcomes of vaccination compared with treatment with antiviral agents alone, in Singapore. METHODOLOGY: We analyzed the economic outcomes of pandemic vaccination (immediate vaccination and vaccine stockpiling compared with treatment-only in Singapore using a decision-based model to perform cost-benefit and cost-effectiveness analyses. We also explored the annual insurance premium (willingness to pay depending on the perceived risk of the next pandemic occurring. PRINCIPAL FINDINGS: The treatment-only strategy resulted in 690 deaths, 13,950 hospitalization days, and economic cost of USD$497 million. For immediate vaccination, at vaccine effectiveness of >55%, vaccination was cost-beneficial over treatment-only. Vaccine stockpiling is not cost-effective in most scenarios even with 100% vaccine effectiveness. The annual insurance premium was highest with immediate vaccination, and was lower with increased duration to the next pandemic. The premium was also higher with higher vaccine effectiveness, attack rates, and case-fatality rates. Stockpiling with case-fatality rates of 0.4-0.6% would be cost-beneficial if vaccine effectiveness was >80%; while at case-fatality of >5% stockpiling would be cost-beneficial even if vaccine effectiveness was 20%. High-risk sub-groups warrant higher premiums than low-risk sub-groups. CONCLUSIONS: The actual pandemic vaccine effectiveness and lead time is unknown. Vaccine strategy should be based on perception of severity. Immediate vaccination is most cost-effective, but requires vaccines to be available when required. Vaccine stockpiling as insurance against worst-case scenarios is also cost-effective. Research and development is therefore critical to develop and stockpile cheap, readily available effective vaccines.
Lee, Vernon J.; Tok, Mei Yin; Chow, Vincent T.; Phua, Kai Hong; Ooi, Eng Eong; Tambyah, Paul A.; Chen, Mark I.
Background All influenza pandemic plans advocate pandemic vaccination. However, few studies have evaluated the cost-effectiveness of different vaccination strategies. This paper compares the economic outcomes of vaccination compared with treatment with antiviral agents alone, in Singapore. Methodology We analyzed the economic outcomes of pandemic vaccination (immediate vaccination and vaccine stockpiling) compared with treatment-only in Singapore using a decision-based model to perform cost-benefit and cost-effectiveness analyses. We also explored the annual insurance premium (willingness to pay) depending on the perceived risk of the next pandemic occurring. Principal Findings The treatment-only strategy resulted in 690 deaths, 13,950 hospitalization days, and economic cost of USD$497 million. For immediate vaccination, at vaccine effectiveness of >55%, vaccination was cost-beneficial over treatment-only. Vaccine stockpiling is not cost-effective in most scenarios even with 100% vaccine effectiveness. The annual insurance premium was highest with immediate vaccination, and was lower with increased duration to the next pandemic. The premium was also higher with higher vaccine effectiveness, attack rates, and case-fatality rates. Stockpiling with case-fatality rates of 0.4–0.6% would be cost-beneficial if vaccine effectiveness was >80%; while at case-fatality of >5% stockpiling would be cost-beneficial even if vaccine effectiveness was 20%. High-risk sub-groups warrant higher premiums than low-risk sub-groups. Conclusions The actual pandemic vaccine effectiveness and lead time is unknown. Vaccine strategy should be based on perception of severity. Immediate vaccination is most cost-effective, but requires vaccines to be available when required. Vaccine stockpiling as insurance against worst-case scenarios is also cost-effective. Research and development is therefore critical to develop and stockpile cheap, readily available effective vaccines. PMID:19771173
Długońska, Henryka; Grzybowski, Marcin
The basic premise of vaccinology is to achieve strong protective immunity against defined infectious agents by a vaccine mimicking the effects of natural primary exposure to a pathogen. Because an exposure of humans and animals to microbes occurs mostly through mucosal surfaces, targeting the mucosa seems a rational and efficient vaccination strategy. Many experimental and clinical data confirmed that mucosal immunization offers many advantages over widely used in human and veterinary medicine subcutaneous or intramuscular immunization. In the present article selected aspects regarding mucosal vaccination are discussed. The structure and function of mucosa-associated lymphoid tissue (MALT), comprised of four main mucosal compartments forming a structural and functional unity as well as pivotal cellular MALT components (dendritic and M cells) were briefly characterized. Particular attention was focused on the mode of simple but efficacious delivery of vaccine antigens to mucosal surfaces. A few trials to generate potential mucosal vaccines against toxoplasmosis introduced by nasal or oral routes to experimental animals are also presented.
Okwor, Ifeoma; Uzonna, Jude
Despite a plethora of publications on the murine model of cutaneous leishmaniasis and their contribution to our understanding of the factors that regulate the development of CD4+ T cell immunity in vivo, there is still no effective vaccine against the human disease. While recovery from natural or experimental infection with Leishmania major, the causative agent of human cutaneous leishmaniasis, results in persistence of parasites at the primary infection site and the development of long-lasting immunity to reinfection, vaccination with killed parasites or recombinant proteins induces only short-term protection. The reasons for the difference in protective immunity following recovery from live infection and vaccination with heat-killed parasites are not known. This may in part be related to persistence of live parasites following healing of primary cutaneous lesions, because complete clearance of parasites leads to rapid loss of infection-induced immunity. Recent reports indicate that in addition to persistent parasites, IL-10-producing natural regulatory T cells may also play critical roles in the maintenance and loss of infection-induced immunity. This review focuses on current understanding of the factors that regulate the development, maintenance and loss of anti-Leishmania memory responses and highlights the role of persistent parasites and regulatory T cells in this process. Understanding these factors is crucial for designing effective vaccines and vaccination strategies against cutaneous leishmaniasis.
Sridhar, Saranya; Brokstad, Karl A.; Cox, Rebecca J.
Influenza is a major respiratory pathogen causing annual outbreaks and occasional pandemics. Influenza vaccination is the major method of prophylaxis. Currently annual influenza vaccination is recommended for groups at high risk of complications from influenza infection such as pregnant women, young children, people with underlying disease and the elderly, along with occupational groups such a healthcare workers and farm workers. There are two main types of vaccines available: the parenteral inactivated influenza vaccine and the intranasal live attenuated influenza vaccine. The inactivated vaccines are licensed from 6 months of age and have been used for more than 50 years with a good safety profile. Inactivated vaccines are standardized according to the presence of the viral major surface glycoprotein hemagglutinin and protection is mediated by the induction of vaccine strain specific antibody responses. In contrast, the live attenuated vaccines are licensed in Europe for children from 2–17 years of age and provide a multifaceted immune response with local and systemic antibody and T cell responses but with no clear correlate of protection. Here we discuss the immunological immune responses elicited by the two vaccines and discuss future work to better define correlates of protection. PMID:26343192
Full Text Available Influenza is a major respiratory pathogen causing annual outbreaks and occasional pandemics. Influenza vaccination is the major method of prophylaxis. Currently annual influenza vaccination is recommended for groups at high risk of complications from influenza infection such as pregnant women, young children, people with underlying disease and the elderly, along with occupational groups such a healthcare workers and farm workers. There are two main types of vaccines available: the parenteral inactivated influenza vaccine and the intranasal live attenuated influenza vaccine. The inactivated vaccines are licensed from 6 months of age and have been used for more than 50 years with a good safety profile. Inactivated vaccines are standardized according to the presence of the viral major surface glycoprotein hemagglutinin and protection is mediated by the induction of vaccine strain specific antibody responses. In contrast, the live attenuated vaccines are licensed in Europe for children from 2–17 years of age and provide a multifaceted immune response with local and systemic antibody and T cell responses but with no clear correlate of protection. Here we discuss the immunological immune responses elicited by the two vaccines and discuss future work to better define correlates of protection.
Wong, Li Ping
Better outcomes of human papillomavirus (HPV) vaccination would be expected if men become full partners and advocates in vaccination initiative. Men involvement has important implication especially within the context that they are equally responsible for spreading the virus. Twenty-seven men took part in four focus group discussions carried out to assess men's attitudes toward the HPV vaccine between October and November 2007. The results revealed that men have low awareness about the newly release vaccine and minimal knowledge of HPV and its association with cervical cancer. When provided with information, most men were in favor of protecting their spouses, partners, or daughters from cervical cancer using the vaccine. They were aware of the effects of men's risk behavioral patterns on women's risk for acquiring HPV infections. Many needed assurance about the vaccine's long-term safety and efficacy. They also expressed concern over the high cost of the vaccine. Men in this study played an influential role in the vaccination decision of their child and sexual partners. Many were in favor of male vaccination for cervical cancer prevention of their spouse or partner. Vaccine advocacy should put special emphasis on men as sexual partners, husbands, and fathers from a gender equality and partnership perspective. The findings are useful in facilitating the development of strategies for effective immunization initiatives.
Jung, Sascha; Patzelt, Alexa; Otberg, Nina; Thiede, Gisela; Sterry, Wolfram; Lademann, Juergen
Liposomes in the nanosize range have been recognized as a versatile drug delivery system of both hydrophilic and lipophilic molecules. In order to develop a liposome-based topical vaccination strategy, five different types of liposomes were tested as a putative vaccine delivery system on pig ear skin. The investigated liposomes mainly varied in size, lipid composition, and surface charge. Using hydrophilic and hydrophobic fluorescent dyes as model drugs, penetration behavior was studied by means of confocal laser scanning microscopy of intact skin and histological sections, respectively. Follicular penetration of the liposomes was measured in comparison to a standard, nonliposomal formulation at different time points. Dependent on time but independent of their different characters, the liposomes showed a significantly higher penetration depth into the hair follicles compared to the standard formulation. The standard formulation reached a relative penetration depth of 30% of the full hair follicle length after seven days, whereas amphoteric and cationic liposomes had reached ~70%. Penetration depth of negatively charged liposomes did not exceed 50% of the total follicle length. The fluorescence dyes were mainly detected in the hair follicle; only a small amount of dye was found in the upper parts of the epidermis.
Roggendorf, H; Freynik, P; Hofmann, F
Vaccination rates in adolescents in Germany are not sufficient. An intervention programme, which has been launched by the community health centre in Essen, should significantly increase vaccination coverage. In 2001 the Children and Youth Health Service at the Community Health Centre in Essen implemented a specific strategy to improve vaccination rates in adolescents. Vaccination rates were determined by control of vaccination certificates of all 6 (th) graders in Essen (n=5 589). After control of vaccination records the parents got a written, individual vaccination counselling for their child as well as a referral to the paediatrician to get the missing vaccinations. After 6 months the vaccination certificates were looked at again and vaccination coverage was determined. At the initial vaccination record control of 6 (th) graders in 2001 only 15% of the students, who presented their vaccination certificate, had an appropriate age related immunisation status. 84% of the students had had the tetanus/diphtheria and polio booster. But only 43% had been given a second measles, mumps and rubella (MMR) immunisation and only 24% had a complete hepatitis B coverage. The intervention programme (e. g., individual vaccination counselling) improved vaccination rates for hepatitis B and MMR by 16%. From 2001 to 2008 vaccination coverage in this age group could be improved from 43% to 87% for the second MMR vaccination and from 24% to 85% for hepatitis B. A remarkable improvement in vaccination coverage in children and adolescents could be achieved by a single, individual, written vaccination reminder. As a prerequisite a good cooperation between schools/paediatricians and the health authorities is needed. © Georg Thieme Verlag KG Stuttgart · New York.
Marc D. Ryser
Full Text Available The effectiveness of vaccinating males against the human papillomavirus (HPV remains a controversial subject. Many existing studies conclude that increasing female coverage is more effective than diverting resources into male vaccination. Recently, several empirical studies on HPV immunization have been published, providing evidence of the fact that marginal vaccination costs increase with coverage. In this study, we use a stochastic agent-based modeling framework to revisit the male vaccination debate in light of these new findings. Within this framework, we assess the impact of coverage-dependent marginal costs of vaccine distribution on optimal immunization strategies against HPV. Focusing on the two scenarios of ongoing and new vaccination programs, we analyze different resource allocation policies and their effects on overall disease burden. Our results suggest that if the costs associated with vaccinating males are relatively close to those associated with vaccinating females, then coverage-dependent, increasing marginal costs may favor vaccination strategies that entail immunization of both genders. In particular, this study emphasizes the necessity for further empirical research on the nature of coverage-dependent vaccination costs.
Ashar, Hanna; Lane, Maureen
A university-based degree completion program for adults conducted focus group research to refine market positioning and promotion. Focus groups averaged five current students and recent graduates who reflected, demographically, the current student population. Results gave insight into reasons for selecting the university, aspects of the program…
Widayani, H.; Kallista, M.; Nuraini, N.; Sari, M. Y.
Dengue fever is emerging tropical and subtropical disease caused by dengue virus infection. The vaccination should be done as a prevention of epidemic in population. The host-vector model are modified with consider a vaccination factor to prevent the occurrence of epidemic dengue in a population. An optimal vaccination strategy using non-linear objective function was proposed. The genetic algorithm programming techniques are combined with fourth-order Runge-Kutta method to construct the optimal vaccination. In this paper, the appropriate vaccination strategy by using the optimal minimum cost function which can reduce the number of epidemic was analyzed. The numerical simulation for some specific cases of vaccination strategy is shown.
Borhani, Kiandokht; Ajorloo, Mehdi; Bamdad, Taravat; Mozhgani, Sayed Hamid Reza; Ghaderi, Mostafa; Gholami, Ali Reza
Rabies is a widespread neurological zoonotic disease causing significant mortality rates, especially in developing countries. Although a vaccine for rabies is available, its production and scheduling are costly in such countries. Advances in recombinant DNA technology have made it a good candidate for an affordable vaccine. Among the proteins of rabies virus, the Glycoprotein (RVG) has been the major target for new vaccine development which plays the principal role in providing complete protection against RV challenge. The aim of this study is to produce recombinant RVG which could be a DNA vaccine candidate and to evaluate the efficiency of this construct in a prime-boost vaccination regimen, compared to commercial vaccine. Cloning to pcDNA3.1(+) and expression of rabies virus glycoprotein gene in BSR cell line were performed followed by SDS-PAGE and Western blot analysis of the expressed glycoprotein. The resulting genetic construct was used as a DNA vaccine by injecting 80 µg of the plasmid to MNRI mice twice. Prime-Boost vaccination strategy was performed using 80 µg plasmid construct as prime dose and the second dose of an inactivated rabies virus vaccine. Production of rabies virus neutralizing antibody (RVNA) titers of the serum samples were determined by RFFIT. In comparisons between heterologous prime-boost vaccination strategy and DNA vaccinations, the potency of group D that received Prime-Boost vaccine with the second dose of pcDNA3.1(+)-Gp was enhanced significantly compared to the group C which had received pcDNA3.1(+)-Gp as first injection. In this study, RVGP expressing construct was used in a comparative approach between Prime-Boost vaccination strategy and DNA vaccination and compared with the standard method of rabies vaccination. It was concluded that this strategy could lead to induction of acceptable humoral immunity.
Davis-Wurzler, Gina M
Vaccines remain one of the practitioner's greatest tools in preventing disease and maintaining individual and population health. This article is an update to "Current Vaccination Strategies in Puppies and Kittens" published in Veterinary Clinics of North America, Small Animal Practitioner, in May 2006. There are now comprehensive guidelines readily available for small animal practitioners regarding canine and feline pediatric (and adult) vaccination recommendations. Perhaps more importantly, there is an increased dialogue regarding all aspects of preventive medicine, of which vaccination is only a small, yet significant portion; and an increased drive to provide scientific evidence for developing vaccination recommendations. Copyright © 2014 Elsevier Inc. All rights reserved.
This paper is concerned with the analysis of vaccination strategies in a stochastic SIR (susceptible $\\to$ infected $\\to$ removed) model for the spread of an epidemic amongst a population of individuals with a random network of social contacts that is also partitioned into households. Under various vaccine action models, we consider both household-based vaccination schemes, in which the way in which individuals are chosen for vaccination depends on the size of the households in which they reside, and acquaintance vaccination, which targets individuals of high degree in the social network. For both types of vaccination scheme, assuming a large population with few initial infectives, we derive a threshold parameter which determines whether or not a large outbreak can occur and also the probability and fraction of the population infected by such an outbreak. The performance of these schemes is studied numerically, focusing on the influence of the household size distribution and the degree distribution of the soc...
Okwor, Ifeoma; Uzonna, Jude
One might think that the development of a vaccine against cutaneous leishmaniasis would be relatively straightforward because the type of immune response required for protection is known and natural immunity occurs following recovery from primary infection. However, there is as yet no effective vaccine against the disease in humans. Although vaccination in murine studies has yielded promising results, these vaccines have failed miserably when tested in primates or humans. The reasons behind these failures are unknown and remain a major hurdle for vaccine design and development against cutaneous leishmaniasis. In contrast, recovery from natural, deliberate or experimental infections results in development of long-lasting immunity to re-infection. This so called infection-induced resistance is the strongest anti-Leishmania immunity known. Here, we briefly review the different approaches to vaccination against cutaneous leishmaniasis and argue that vaccines composed of genetically modified (attenuated) parasites, which induce immunity akin to infection-induced resistance, may provide best protection against cutaneous leishmaniasis in humans.
Chattha, Kuldeep S; Roth, James A; Saif, Linda J
Enteric viral infections in domestic animals cause significant economic losses. The recent emergence of virulent enteric coronaviruses [porcine epidemic diarrhea virus (PEDV)] in North America and Asia, for which no vaccines are available, remains a challenge for the global swine industry. Vaccination strategies against rotavirus and coronavirus (transmissible gastroenteritis virus) infections are reviewed. These vaccination principles are applicable against emerging enteric infections such as PEDV. Maternal vaccines to induce lactogenic immunity, and their transmission to suckling neonates via colostrum and milk, are critical for early passive protection. Subsequently, in weaned animals, oral vaccines incorporating novel mucosal adjuvants (e.g., vitamin A, probiotics) may provide active protection when maternal immunity wanes. Understanding intestinal and systemic immune responses to experimental rotavirus and transmissible gastroenteritis virus vaccines and infection in pigs provides a basis and model for the development of safe and effective vaccines for young animals and children against established and emerging enteric infections.
Jefferies, Johanna M C; Clarke, Stuart C; Webb, Jeremy S; Kraaijeveld, Alex R
Pathogens increasingly evade current vaccines, and new strategies to control them are needed. There is mounting evidence that replacement of vaccine serotypes of Streptococcus pneumoniae with non-vaccine serotypes has taken place following widespread use of limited-serotype conjugate vaccines. New strategies to control vaccine evasion are needed and understanding evolutionary theory is important for the development of such approaches. Hosts are under selection pressure to evolve resistance against pathogens whereas pathogens are under selection pressure to evolve counter-resistance against the resistance mechanism of their host. Evolutionary changes in both host and pathogen lead to a continuous turnover of host and pathogen genotypes; this is known as Red Queen dynamics. We argue that integrating evolutionary thinking into pneumococcal vaccine design will lead to the avoidance of Red Queen dynamics and improved interventions against pneumococci. Copyright © 2011 Elsevier Ltd. All rights reserved.
Keeling, M. J.; Woolhouse, M. E. J.; May, R. M.; Davies, G.; Grenfell, B. T.
Vaccination has proved a powerful defence against a range of infectious diseases of humans and animals. However, its potential to control major epidemics of foot-and-mouth disease (FMD) in livestock is contentious. Using an individual farm-based model, we consider either national prophylactic vaccination campaigns in advance of an outbreak, or combinations of reactive vaccination and culling strategies during an epidemic. Consistent with standard epidemiological theory, mass prophylactic vaccination could reduce greatly the potential for a major epidemic, while the targeting of high-risk farms increases efficiency. Given sufficient resources and preparation, a combination of reactive vaccination and culling might control ongoing epidemics. We also explore a reactive strategy, `predictive' vaccination, which targets key spatial transmission loci and can reduce markedly the long tail that characterizes many FMD epidemics. These analyses have broader implications for the control of human and livestock infectious diseases in heterogeneous spatial landscapes.
Kim, Kyounghae; Kim, Boyoung; Choi, Eunsuk; Song, Youngshin; Han, Hae-Ra
As one of the fastest growing ethnic minority groups in the United States, Korean American (KA) women experience a heightened cervical cancer burden. The advent of the human papillomavirus (HPV) vaccine offers an unprecedented opportunity to eliminate cervical cancer disparities in KA women. However, the uptake of HPV vaccine among KA adolescents remains suboptimal. Hence, we set out to explore knowledge, perceptions, and decision making about HPV vaccination among KA women. We conducted four focus groups of 26 KA women who participated in a community-based, randomized, controlled trial to promote breast and cervical cancer screening. Focus group data were analyzed using qualitative content analysis. Four main themes emerged from the focus groups: 1) limited awareness and knowledge of HPV vaccine, 2) perceptions and beliefs about HPV vaccination (acceptance, negative perceptions, ambivalence), 3) patterns of decision making about HPV vaccination (hierarchical, peer influenced, autonomous, and collaborative), and 4) promoting HPV education and information sharing in the Korean community. KA women are generally positive toward HPV vaccination, but lack awareness and knowledge about HPV. Culturally tailored HPV education programs based on KA women's decision-making patterns and effective information sharing by trustworthy sources in comfortable environments are suggested strategies to promote HPV vaccination in the KA community. The findings point to the need for a multilevel approach to addressing linguistic, cultural, and system barriers that the recent immigrant community faces in promoting HPV vaccinations. In the development of targeted interventions for KA women, educational strategies and patterns of decision making need to be considered. Copyright © 2015 Jacobs Institute of Women's Health. Published by Elsevier Inc. All rights reserved.
Background: National vaccination campaigns prevented yellow fever virus epidemics in Nigeria. A build-up of Aedes aegypti mosquitoes have been found in parts of the rain forest region that was the hotbed of previous epidemics. This study provides information on the annual vaccination counts in some major vaccination ...
Durbin, Anna P
Zika virus is a mosquito-borne Flavivirus that spread rapidly through South and Central America in 2015 to 2016. Microcephaly has been causally associated with Zika virus infection during pregnancy and the World Health Organization declared Zika virus as a Public Health Emergency of International Concern. To address this crisis, many groups have expressed their commitment to developing a Zika virus vaccine. Different strategies for Zika virus vaccine development are being considered including recombinant live attenuated vaccines, purified inactivated vaccines (PIVs), DNA vaccines, and viral vectored vaccines. Important to Zika virus vaccine development will be the target group chosen for vaccination and which end point(s) is chosen for efficacy determination. The first clinical trials of Zika virus vaccine candidates will begin in Q3/4 2016 but the pathway to licensure for a Zika virus vaccine is expected to take several years. Efforts are ongoing to accelerate Zika virus vaccine development and evaluation with the ultimate goal of reducing time to licensure. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
Græsbøll, Kaare; Enøe, Claes; Bødker, Rene
Using a process oriented semi-agent based model, we simulated the spread of Bluetongue virus by Culicoides, biting midges, between cattle in Denmark. We evaluated the minimum vaccination cover and minimum cost for eight different preventive vaccination strategies in Denmark. The simulation model...
Full Text Available ABSTRAKPenyakit demam Dengue endemik di lebih dari 100 negara di dunia. Obat anti virus Dengue efektif belum ditemukan danpengendalian vektor dinilai kurang efektif, sehingga diperlukan upaya pencegahan dengan vaksinasi. Vaksin Dengue yangideal adalah murah, mencakup 4 serotipe, efektif dalam memberikan kekebalan, cukup diberikan sekali seumur hidup, aman,memberi kekebalan jangka panjang, stabil dalam penyimpanan dan stabil secara genetis (tidak bermutasi. Beberapakandidat vaksin yang telah dan sedang dikembangkan oleh para peneliti di seluruh dunia adalah tetravalent live attenuatedvaccine, vaksin Chimera (ChimeriVax, vaksin subunit dan vaksin DNA. Vaksin Dengue dipandang sebagai pendekatan yangefektif dan berkesinambungan dalam mengendalikan penyakit Dengue. Tahun 2003 telah terbentuk Pediatric DengueVaccine Initiative (PDVI, yaitu sebuah konsorsium internasional yang bergerak dalam advokasi untuk meyakinkanmasyarakat internasional akan penting dan mendesaknya vaksin Dengue. Konsorsium vaksin Dengue Indonesia saat iniberupaya mengembangkan vaksin Dengue dengan menggunakan strain virus lokal.Kata kunci: Dengue, virus, vaksinABSTRACTDengue fever is endemic in more than 100 countries in the world. The effective dengue antiviral drug has not been found yet,and vector control is considered less effective. Prevention program by vaccination is needed. An ideal dengue vaccine shouldbe inexpensive, covering four serotypes (tetravalent, effective in providing immunity, given once a lifetime, safe, stable instorage and genetically. Several vaccine candidates have been and are being developed included attenuated tetravalentvaccine, ChimeriVax, sub- unit vaccines and DNA vaccines. Dengue vaccine is seen as an effective and sustainable approachto controll Dengue infection. In 2003, Pediatric Dengue Vaccine Initiative (PDVI has been formed as an internationalconsortium involved in advocacy to convince the international community about the essence and urgency
has been the pneumococcal conjugate vaccines (PCVs) – the main focus of this article. Pneumococcal conjugate vaccines. Accumulated evidence suggests that the 13valent PCV (PCV13) has reduced much of the residual burden of pneumococcal diseases still present in children after the introduction of PCV7. This ...
Antón, F; Richart, M J; Serrano, S; Martínez, A M; Pruteanu, D F
Vaccination coverage reached in adults is insufficient, and there is a real need for new strategies. To compare strategies for improving influenza vaccination coverage in persons older than 64 years. New strategies were introduced in our health care centre during 2013-2014 influenza vaccination campaign, which included vaccinating patients in homes for the aged as well as in the health care centre. A comparison was made on vaccination coverage over the last 4 years in 3 practices of our health care centre: P1, the general physician vaccinated patients older than 64 that came to the practice; P2, the general physician systematically insisted in vaccination in elderly patients, strongly advising to book appointments, and P3, the general physician did not insist. These practices looked after P1: 278; P2: 320; P3: 294 patients older than 64 years. Overall/P1/P2/P3 coverages in 2010: 51.2/51.4/55/46.9% (P=NS), in 2011: 52.4/52.9/53.8/50.3% (P=NS), in 2012: 51.9/52.5/55.3/47.6% (P=NS), and in 2013: 63.5/79.1/59.7/52.7 (P=.000, P1 versus P2 and P3; P=NS between P2 and P3). Comparing the coverages in 2012-2013 within each practice P1 (P=.000); P2 (P=.045); P3 (P=.018). In P2 and P3 all vaccinations were given by the nurses as previously scheduled. In P3, 55% of the vaccinations were given by the nurses, 24.1% by the GP, 9.7% rejected vaccination, and the remainder did not come to the practice during the vaccination period (October 2013-February 2014). The strategy of vaccinating in the homes for the aged improved the vaccination coverage by 5% in each practice. The strategy of "I've got you here, I jab you here" in P1 improved the vaccination coverage by 22%. Copyright © 2014 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.
Farrukh, Muhammad Junaid; Ming, Long Chiau; Zaidi, Syed Tabish Razi; Khan, Tahir Mehmood
Influenza vaccination is strongly recommended by World Health Organisation on a yearly basis. The rate of immunization in Pakistan is suboptimal. High cost, traditional norms, customs and low levels of education in Pakistan are preventing people from getting vaccinated. It is timely to include influenza vaccination in the expanded programme on immunization (EPI), which is a disease prevention programme aiming to eradicate preventable diseases through subsidized or free immunization. The Ministry of National Health Services, Regulation and Coordination, Government of Pakistan should launch a national influenza vaccine policy in view of this current situation and oversee its implementation. Healthcare professionals should promote influenza vaccination and focus on high risk groups such as the elderly, pregnant women and children. Convincing and educating family members regarding immunization of pregnant women and follow-up with parents regarding a second influenza shot for their children will further improve vaccination rates in Pakistan. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.
Full Text Available High-risk types of human papillomavirus (HPV cause over 500,000 cervical, anogenital and oropharyngeal cancer cases per year. The transforming potential of HPVs is mediated by viral oncoproteins. These are essential for the induction and maintenance of the malignant phenotype. Thus, HPV-mediated malignancies pose the unique opportunity in cancer vaccination to target immunologically foreign epitopes. Therapeutic HPV vaccination is therefore an ideal scenario for proof-of-concept studies of cancer immunotherapy. This is reflected by the fact that a multitude of approaches has been utilized in therapeutic HPV vaccination design: protein and peptide vaccination, DNA vaccination, nanoparticle- and cell-based vaccines, and live viral and bacterial vectors. This review provides a comprehensive overview of completed and ongoing clinical trials in therapeutic HPV vaccination (summarized in tables, and also highlights selected promising preclinical studies. Special emphasis is given to adjuvant science and the potential impact of novel developments in vaccinology research, such as combination therapies to overcome tumor immune suppression, the use of novel materials and mouse models, as well as systems vaccinology and immunogenetics approaches.
Khallouf, Hadeel; Grabowska, Agnieszka K.; Riemer, Angelika B.
High-risk types of human papillomavirus (HPV) cause over 500,000 cervical, anogenital and oropharyngeal cancer cases per year. The transforming potential of HPVs is mediated by viral oncoproteins. These are essential for the induction and maintenance of the malignant phenotype. Thus, HPV-mediated malignancies pose the unique opportunity in cancer vaccination to target immunologically foreign epitopes. Therapeutic HPV vaccination is therefore an ideal scenario for proof-of-concept studies of cancer immunotherapy. This is reflected by the fact that a multitude of approaches has been utilized in therapeutic HPV vaccination design: protein and peptide vaccination, DNA vaccination, nanoparticle- and cell-based vaccines, and live viral and bacterial vectors. This review provides a comprehensive overview of completed and ongoing clinical trials in therapeutic HPV vaccination (summarized in tables), and also highlights selected promising preclinical studies. Special emphasis is given to adjuvant science and the potential impact of novel developments in vaccinology research, such as combination therapies to overcome tumor immune suppression, the use of novel materials and mouse models, as well as systems vaccinology and immunogenetics approaches. PMID:26344626
Ashleigh R Tuite
Full Text Available BACKGROUND: The world is currently confronting the first influenza pandemic of the 21(st century. Influenza vaccination is an effective preventive measure, but the unique epidemiological features of swine-origin influenza A (H1N1 (pH1N1 introduce uncertainty as to the best strategy for prioritization of vaccine allocation. We sought to determine optimal prioritization of vaccine distribution among different age and risk groups within the Canadian population, to minimize influenza-attributable morbidity and mortality. METHODOLOGY/PRINCIPAL FINDINGS: We developed a deterministic, age-structured compartmental model of influenza transmission, with key parameter values estimated from data collected during the initial phase of the epidemic in Ontario, Canada. We examined the effect of different vaccination strategies on attack rates, hospitalizations, intensive care unit admissions, and mortality. In all scenarios, prioritization of high-risk individuals (those with underlying chronic conditions and pregnant women, regardless of age, markedly decreased the frequency of severe outcomes. When individuals with underlying medical conditions were not prioritized and an age group-based approach was used, preferential vaccination of age groups at increased risk of severe outcomes following infection generally resulted in decreased mortality compared to targeting vaccine to age groups with higher transmission, at a cost of higher population-level attack rates. All simulations were sensitive to the timing of the epidemic peak in relation to vaccine availability, with vaccination having the greatest impact when it was implemented well in advance of the epidemic peak. CONCLUSIONS/SIGNIFICANCE: Our model simulations suggest that vaccine should be allocated to high-risk groups, regardless of age, followed by age groups at increased risk of severe outcomes. Vaccination may significantly reduce influenza-attributable morbidity and mortality, but the benefits are
Treanor, John J; Johnson, Joseph S; Wallen, Rick L; Cilles, Sara; Crowley, Philip H; Cox, John J; Maehr, David S; White, P J; Plumb, Glenn E
Concerns over migratory bison (Bison bison) at Yellowstone National Park transmitting brucellosis (Brucella abortus) to cattle herds on adjacent lands led to proposals for bison vaccination. We developed an individual-based model to evaluate how brucellosis infection might respond under alternate vaccination strategies, including: (1) vaccination of female calves and yearlings captured at the park boundary when bison move outside the primary conservation area; (2) combining boundary vaccination with the remote delivery of vaccine to female calves and yearlings distributed throughout the park; and (3) vaccinating all female bison (including adults) during boundary capture and throughout the park using remote delivery of vaccine. Simulations suggested Alternative 3 would be most effective, with brucellosis seroprevalence decreasing by 66% (from 0.47 to 0.16) over a 30-year period resulting from 29% of the population receiving protection through vaccination. Under this alternative, bison would receive multiple vaccinations that extend the duration of vaccine protection and defend against recurring infection in latently infected animals. The initial decrease in population seroprevalence will likely be slow due to high initial seroprevalence (40-60%), long-lived antibodies, and the culling of some vaccinated bison that were subsequently exposed to field strain Brucella and reacted positively on serologic tests. Vaccination is unlikely to eradicate B. abortus from Yellowstone bison, but could be an effective tool for reducing the level of infection. Our approach and findings have applicability world-wide for managers dealing with intractable wildlife diseases that cross wildlife-livestock and wildlife-human interfaces and affect public health or economic well-being. Published by Elsevier Ltd.
Ntege, Edward H; Takashima, Eizo; Morita, Masayuki; Nagaoka, Hikaru; Ishino, Tomoko; Tsuboi, Takafumi
An efficacious malaria vaccine is necessary to advance the current control measures towards malaria elimination. To-date, only RTS,S/AS01, a leading pre-erythrocytic stage vaccine completed phase 3 trials, but with an efficacy of 28-36% in children, and 18-26% in infants, that waned over time. Blood-stage malaria vaccines protect against disease, and are considered effective targets for the logical design of next generation vaccines to improve the RTS,S field efficacy. Therefore, novel blood-stage vaccine candidate discovery efforts are critical, albeit with several challenges including, high polymorphisms in vaccine antigens, poor understanding of targets of naturally protective immunity, and difficulties in the expression of high AT-rich plasmodial proteins. Areas covered: PubMed ( www.ncbi.nlm.nih.gov/pubmed ) was searched to review the progress and future prospects of malaria vaccine research and development. We focused on post-genome vaccine candidate discovery, malaria vaccine development, sequence diversity, pre-clinical and clinical trials. Expert commentary: Post-genome high-throughput technologies using wheat germ cell-free protein synthesis technology and immuno-profiling with sera from malaria patients with clearly defined outcomes are highlighted to overcome current challenges of malaria vaccine candidate discovery.
Schroeder, Charles C.
When institutions engage in discussions regarding improving retention and graduation rates, invariably the conversation focuses on entering student characteristics, especially ACT and SAT scores and high school grades. Clearly, attracting and enrolling well-prepared and motivated high-ability students will certainly improve institutional measures…
Mehta, Purvi; Sharma, Manoj; Lee, Rebecca C
This study determines predictors of HPV vaccine acceptability among college-aged male students through the qualitative data collection strategy of focus groups. Over the course of 2 months, six focus groups were conducted with 50 participants, with approximately 10 participants in each focus group. Participants were predominately single, heterosexual, about 20 years old, Caucasian males attending a large Midwestern University. The Health Belief Model (HBM) was used as a guide in developing questions for the focus groups. Each question related to a construct of the HBM. A lack of perceived susceptibility, perceived severity of HPV, and barriers toward taking the HPV vaccine were major themes identified from the focus groups. Overall, the focus group proved to be effective in understanding predictors toward HPV vaccine acceptability. Results enabled the researchers to develop an understanding of content needed for effective interventions. This study indicates a need for more qualitative studies exploring attitudes, beliefs, and behaviors related to HPV vaccine acceptability among at-risk populations.
M. De la Sen; A. Ibeas; S. Alonso-Quesada
A linearization-based feedback-control strategy for a SEIR epidemic model is discussed. The vaccination objective is the asymptotically tracking of the removed-by-immunity population to the total population while achieving simultaneously the remaining population (i.e. susceptible plus infected plus infectious) to asymptotically tend to zero. The disease controlpolicy is designed based on a feedback linearization technique which provides a general method to generate families of vaccination pol...
Simeonsson, Kristina; Summers-Bean, Chris; Connolly, Allison
The nosocomial transmission of influenza has been well documented since the 1970s with both direct and indirect effects of outbreaks in healthcare settings. Outbreaks can directly increase morbidity among patients and residents of long-term care facilities. Indirect effects include disruption of normal operations of healthcare institutions, shortages of healthcare workers (HCWs), fewer elective admissions, and income loss due to absenteeism. Influenza vaccination of United States HCWs remains below 40% despite the availability of a safe, effective vaccine and a long-standing recommendation for vaccination of HCWs. New strategies to improve the rate of influenza vaccination among HCWs are needed as the percentage of those receiving yearly vaccination has changed little in the past 20 years. Increasing HCW influenza vaccination coverage calls for a paradigm shift, institutions should view vaccination of HCWs as a crucial part of a comprehensive infection control program designed to protect patients and staff. Administrators of hospitals, long-term care facilities, and other health agencies should respond to this challenge by developing programs to improve yearly influenza vaccination of their staff Such efforts would put these employees into compliance with national recommendations and also benefit the institution by reducing absenteeism, nosocomial influenza transmission, and the associated economic losses and disruption of routine operations.
Harmsen, Irene A; Mollema, Liesbeth; Ruiter, Robert A C; Paulussen, Theo G W; de Melker, Hester E; Kok, Gerjo
In high income countries, vaccine-preventable diseases have been greatly reduced through routine vaccination programs. Despite this success, many parents question, and a small proportion even refuse vaccination for their children. As no qualitative studies have explored the factors behind these decisions among Dutch parents, we performed a study using online focus groups. In total, eight online focus groups (n = 60) which included Dutch parents with at least one child, aged 0-4 years, for whom they refused all or part of the vaccinations within the National Immunization Program (NIP). A thematic analysis was performed to explore factors that influenced the parents' decisions to refuse vaccination. Refusal of vaccination was found to reflect multiple factors including family lifestyle; perceptions about the child's body and immune system; perceived risks of disease, vaccine efficacy, and side effects; perceived advantages of experiencing the disease; prior negative experience with vaccination; and social environment. The use of online focus groups proved to be an effective qualitative research method providing meaningful data. Information provided by the NIP turned out to be insufficient for this group of parents. More trust in the NIP and deliberate decisions might result from increased parental understanding of lifestyle and disease susceptibility, the impact of vaccinations on the immune system, and the relative risks of diseases and their vaccines. The public health institute should also inform parents that the NIP is recommended but non-mandatory.
Chaerani, D., E-mail: firstname.lastname@example.org; Anggriani, N., E-mail: email@example.com; Firdaniza, E-mail: firstname.lastname@example.org [Department of Mathematics, Faculty of Mathematics and Natural Sciences, University of Padjadjaran Indonesia, Jalan Raya Bandung Sumedang KM 21 Jatinangor Sumedang 45363 (Indonesia)
In order to prevent an epidemic of infectious diseases, the vaccination coverage needs to be minimized and also the basic reproduction number needs to be maintained below 1. This means that as we get the vaccination coverage as minimum as possible, thus we need to prevent the epidemic to a small number of people who already get infected. In this paper, we discuss the case of vaccination strategy in term of minimizing vaccination coverage, when the basic reproduction number is assumed as an uncertain parameter that lies between 0 and 1. We refer to the linear optimization model for vaccination strategy that propose by Becker and Starrzak (see ). Assuming that there is parameter uncertainty involved, we can see Tanner et al (see ) who propose the optimal solution of the problem using stochastic programming. In this paper we discuss an alternative way of optimizing the uncertain vaccination strategy using Robust Optimization (see ). In this approach we assume that the parameter uncertainty lies within an ellipsoidal uncertainty set such that we can claim that the obtained result will be achieved in a polynomial time algorithm (as it is guaranteed by the RO methodology). The robust counterpart model is presented.
Moraga-Llop, Fernando A; Mendoza-Palomar, Natàlia; Muntaner-Alonso, Antoni; Codina-Grau, Gemma; Fàbregas-Martori, Anna; Campins-Martí, Magda
To analyse the vaccination status of children diagnosed with pertussis and to compare the clinical manifestations of fully vaccinated with unvaccinated, or incompletely-vaccinated, children. The clinical histories and vaccination cards of patients under 16years of age seen in the Emergency Room of the University Hospital Vall d'Hebron, Barcelona (Spain), for pertussis confirmed by a microbiological study were reviewed. The study period lasted from January 1, 2009 to December 31, 2011. Two hundred and twelve cases were studied: 35 in 2009, 28 in 2010 and 149 in 2011. RT-PCR was positive in 210 patients, and 73 had a positive culture. Infants under 6months of age account for 36.8% of all cases. Forty-four patients (21.5%) were not vaccinated. Forty-four (21.5%) children were between 2 and 5months of age and had received 1-2vaccine doses. One hundred and seventeen (57%) children were fully vaccinated; 76.9% (90cases) had received the last dose less than 4years ago. When clinical manifestations of the fully vaccinated patients were compared with those of the non-vaccinated or incompletely-vaccinated children, only cyanosis was found with a higher frequency in the latter group (P<.001). The age-adjusted probability of hospitalisation was significantly associated with non-vaccination (P=.001). The case mortality rate among inpatients was 1.3%. The number of pertussis cases seen in our centre has risen significantly in the last year. More than half (57%) of the patients were fully vaccinated, and 76.9% had received the last dose in the previous 4years. Other vaccination strategies, such as vaccination of adolescents, adults, and pregnant women, as well as a cocoon strategy are required to protect infants under 6months of age. More effective vaccines need to be developed. Copyright © 2012 Elsevier España, S.L. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.
Neosporosis is caused by the intracellular protozoan parasite Neospora caninum. This major disease-causing pathogen is responsible for inducing abortion in cattle, and these adverse events occur sporadically all over the world, including Japan. Currently, there are no vaccines on the market against infection with N. caninum. Because live and attenuated vaccines against N. caninum have had safety and effectiveness issues, development of a next-generation vaccine is urgently required. To develop a vaccine against neosporosis, my laboratory has been focused on the following: 1) understanding the host immune responses against Neospora infection, 2) identifying vaccine antigens and 3) developing an effective antigen-delivery system. The research strategy taken in my laboratory will have strong potential to progress current understanding of the pathogenesis of N. caninum infection and promote development of a novel subunit vaccine based on the specific vaccine antigen with an antigen-delivery system for controlling neosporosis.
McKay, M. A.; Jenson, L.; Kovac, S. A.; Bosh, R.; Mitchell, A. M.; Hare, H. S.; Watson, Z.; Penn, M. J.
The 2017 solar eclipse will be a natural phenomenon that will sweep across the United State would provide an excellent opportunity to observe and study the solar corona. The Citizens Continental Astronomical Telescopic Eclipse (CATE) Experiment directed my Matt Penn, intends to take advantage of this scientific opportunity by organizing 60 sites along the path of totality from Oregon to South Carolina to observe the eclipse and make a 90 min continuous video of the solar corona. The preliminary observation was done with the 2016 eclipse in Indonesia, with 5 sites along the path of totality. The sites were provided with an 80mm diameter Telescope with a 480mm focal length with an extension tube, Celestron equatorial mount, a CMOS camera, a Dell dual processor running Windows, GPS and an Arduino box, more details will be provided. I observed at the furthest east site in Ternate, Indonesia, with Dr. Donald Walter. The day of the eclipse we had clouds but still had a successful observation. The observation was successful with 4 out of the 5 sites collected eclipse data, due to weather the other site was not able to observe. The data was then collected and processed over the summer. To prepare for the observation in 2017, the 60 sites will be provided with the equipment, software and training. The groups will then practice by doing solar and lunar observations, where they will follow an almost identical procedure for the eclipse to do their observations. These test will increase our chances to have a successful observation among all sites. The focus will play a crucial role in this observation to provide a high quality image. Currently, a new focusing method using an image derivative method to provide quantitative feedback to the user is being developed. Finally, a Graphical User Interface is also being developed using the codes produces from the summer 2016 data analysis, to process the images from each site with minimal effort and produce quality scientific images
Almuzakki, Muhammad Zaki; Nuraini, Nuning
A combination between Susceptible-Exposed-Infected-Removed (SEIR) model and Cellular Automaton (CA) called SEIR-CA model has been proposed to simulate spreading diseases through populations. We make an improvement to the parameter which describe the impact of neighborhood in CA system. We also propose a vaccination strategy to the model. Three examples are given to illustrate the model. The first one shows that the previously established SEIR-CA model does not work properly in a population with randomly distributed individuals. After an improvement to the neighborhood impact parameter has been made, the model works properly in a population with randomly distributed individuals and it is shown in the second example. The last example shows the spreading mechanisms with a chosen vaccination strategy. We also show that the vaccination strategy can reduce the number of infected individuals and can suppress the spread of the diseases.
Full Text Available Henricus LBM (Eric Klaasen,1 Ben Adler2 1Global Companion Animals Research and Development, Merck Sharp and Dohme Animal Health, Boxmeer, the Netherlands; 2Department of Microbiology, Monash University, Clayton, VIC, Australia Abstract: Leptospirosis is a global infection of humans and animals caused by pathogenic Leptospira spp. Leptospirosis is a major zoonosis, with infection acquired from wild and domestic animals. It is also a significant cause of morbidity, mortality, and economic loss in production and companion animals. Leptospirosis in dogs is prevalent worldwide and as well as a cause of canine disease, it presents a zoonotic risk to human contacts. Canine leptospirosis does not differ greatly from the syndromes seen in other animal species, with hepatic, renal, and pulmonary involvement being the main manifestations. While the pathogenesis of disease is well documented at the whole animal level, the cellular and molecular basis remains obscure. Killed, whole-cell bacterin vaccines are licensed worldwide and have not changed greatly over the past several decades. Vaccine-induced immunity is restricted to serologically related serovars and is generally short-lived, necessitating annual revaccination. The appearance of new serovars as causes of canine leptospirosis requires constant epidemiological surveillance and tailoring of vaccines to cover emerging serovars. At the present time, there is no realistic prospect of alternative, non-bacterin vaccines in the foreseeable future. Keywords: canine leptospirosis, vaccines, diagnosis, epidemiology, pathogenesis
Glasser, John; Taneri, Denis; Feng, Zhilan; Chuang, Jen-Hsiang; Tüll, Peet; Thompson, William; Mason McCauley, Mary; Alexander, James
Background Because they can generate comparable predictions, mathematical models are ideal tools for evaluating alternative drug or vaccine allocation strategies. To remain credible, however, results must be consistent. Authors of a recent assessment of possible influenza vaccination strategies conclude that older children, adolescents, and young adults are the optimal targets, no matter the objective, and argue for vaccinating them. Authors of two earlier studies concluded, respectively, that optimal targets depend on objectives and cautioned against changing policy. Which should we believe? Methods and Findings In matrices whose elements are contacts between persons by age, the main diagonal always predominates, reflecting contacts between contemporaries. Indirect effects (e.g., impacts of vaccinating one group on morbidity or mortality in others) result from off-diagonal elements. Mixing matrices based on periods in proximity with others have greater sub- and super-diagonals, reflecting contacts between parents and children, and other off-diagonal elements (reflecting, e.g., age-independent contacts among co-workers), than those based on face-to-face conversations. To assess the impact of targeted vaccination, we used a time-usage study's mixing matrix and allowed vaccine efficacy to vary with age. And we derived mortality rates either by dividing observed deaths attributed to pneumonia and influenza by average annual cases from a demographically-realistic SEIRS model or by multiplying those rates by ratios of (versus adding to them differences between) pandemic and pre-pandemic mortalities. Conclusions In our simulations, vaccinating older children, adolescents, and young adults averts the most cases, but vaccinating either younger children and older adults or young adults averts the most deaths, depending on the age distribution of mortality. These results are consistent with those of the earlier studies. PMID:20862297
Full Text Available BACKGROUND: Because they can generate comparable predictions, mathematical models are ideal tools for evaluating alternative drug or vaccine allocation strategies. To remain credible, however, results must be consistent. Authors of a recent assessment of possible influenza vaccination strategies conclude that older children, adolescents, and young adults are the optimal targets, no matter the objective, and argue for vaccinating them. Authors of two earlier studies concluded, respectively, that optimal targets depend on objectives and cautioned against changing policy. Which should we believe? METHODS AND FINDINGS: In matrices whose elements are contacts between persons by age, the main diagonal always predominates, reflecting contacts between contemporaries. Indirect effects (e.g., impacts of vaccinating one group on morbidity or mortality in others result from off-diagonal elements. Mixing matrices based on periods in proximity with others have greater sub- and super-diagonals, reflecting contacts between parents and children, and other off-diagonal elements (reflecting, e.g., age-independent contacts among co-workers, than those based on face-to-face conversations. To assess the impact of targeted vaccination, we used a time-usage study's mixing matrix and allowed vaccine efficacy to vary with age. And we derived mortality rates either by dividing observed deaths attributed to pneumonia and influenza by average annual cases from a demographically-realistic SEIRS model or by multiplying those rates by ratios of (versus adding to them differences between pandemic and pre-pandemic mortalities. CONCLUSIONS: In our simulations, vaccinating older children, adolescents, and young adults averts the most cases, but vaccinating either younger children and older adults or young adults averts the most deaths, depending on the age distribution of mortality. These results are consistent with those of the earlier studies.
Li, Junping; Yang, Tao; Xu, Qingyuan; Sun, Encheng; Feng, Yufei; Lv, Shuang; Zhang, Qin; Wang, Haixiu; Wu, Donglai
Bluetongue virus (BTV) is the causative agent of bluetongue (BT), an important sheep disease that caused great economic loss to the sheep industry. There are 26 BTV serotypes based on the outer protein VP2. However, the serotypes BTV-1 and BTV-16 are the two most prevalent serotypes in China. Vaccination is the most effective method of preventing viral infections. Therefore, the need for an effective vaccine against BTV is urgent. In this study, DNA vaccines and recombinant fowlpox virus (rFPV) vaccines expressing VP2 alone or VP2 in combination with VP5 or co-expressing the VP2 and VP5 proteins of BTV-1 were evaluated in both mice and sheep. Several strategies were tested in mice, including DNA vaccine prime and boost, rFPV vaccine prime and boost, and DNA vaccine prime and rFPV vaccine boost. We then determined the best vaccine strategy in sheep. Our results indicated that a strategy combining a DNA vaccine prime (co-expressing VP2 and VP5) followed by an rFPV vaccine boost (co-expressing VP2 and VP5) induced a high titer of neutralizing antibodies in sheep. Therefore, our data suggest that a DNA vaccine consisting of a pCAG-(VP2+VP5) prime and an rFPV-(VP2+VP5) boost is an important candidate for the design of a novel vaccine against BTV-1.
Liu, Siyu; Li, Yong; Bi, Yingjie; Huang, Qingdao
This study first presents a mathematical model of TB transmission considering BCG vaccination compartment to investigate the transmission dynamics nowadays. Based on data reported by the National Bureau of Statistics of China, the basic reproduction number is estimated approximately as R0=1.1892. To reach the new End TB goal raised by WHO in 2015, considering the health system in China, we design a mixed vaccination strategy. Theoretical analysis indicates that the infectious population asymptotically tends to zero with the new vaccination strategy which is the combination of constant vaccination and pulse vaccination. We obtain that the control of TB is quicker to achieve with the mixed vaccination. The new strategy can make the best of current constant vaccination, and the periodic routine health examination provides an operable environment for implementing pulse vaccination in China. Numerical simulations are provided to illustrate the theoretical results and help to design the final mixed vaccination strategy once the new vaccine comes out.
Zhang, Tailei; Teng, Zhidong
The aim of this paper is to analyze an SIRVS epidemic model in which pulse vaccination strategy (PVS) is included. We are interested in finding the basic reproductive number of the model which determine whether or not the disease dies out. The global attractivity of the disease-free periodic solution (DFPS for short) is obtained when the basic reproductive number is less than unity. The disease is permanent when the basic reproductive number is greater than unity, i.e., the epidemic will turn out to endemic. Our results indicate that the disease will go to extinction when the vaccination rate reaches some critical value.
Zhang, Ying; Deng, Jian; Feng, Jun; Wu, Feng
AIM: To investigate whether tumor debris created by high-intensity focused ultrasound (HIFU) could trigger antitumor immunity in a mouse hepatocellular carcinoma model. METHODS: Twenty C57BL/6J mice bearing H22 hepatocellular carcinoma were used to generate antitumor vaccines. Ten mice underwent HIFU ablation, and the remaining 10 mice received a sham-HIFU procedure with no ultrasound irradiation. Sixty normal mice were randomly divided into HIFU vaccine, tumor vaccine and control groups. These mice were immunized with HIFU-generated vaccine, tumor-generated vaccine, and saline, respectively. In addition, 20 mice bearing H22 tumors were successfully treated with HIFU ablation. The protective immunity of the vaccinated mice was investigated before and after a subsequent H22 tumor challenge. Using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, the cytotoxicity of splenic lymphocytes co-cultured with H22 cells was determined in vitro before the tumor challenge, and tumor volume and survival were measured in vivo after the challenge in each group. The mechanism was also explored by loading the vaccines with bone marrow-derived dendritic cells (DCs). RESULTS: Compared to the control, HIFU therapy, tumor-generated and HIFU-generated vaccines significantly increased cytolytic activity against H22 cells in the splenocytes of the vaccinated mice (P HIFU vaccine group than in the tumor vaccine group (P HIFU therapy group. Forty-eight-day survival rate was 100% in mice in the HIFU therapy group, 30% in both the HIFU vaccine and tumor vaccine groups, and 20% in the control group, indicating that the HIFU-treated mice displayed significantly longer survival than the vaccinated mice in the remaining three groups (P HIFU-generated and tumor-generated vaccines, the number of mature DCs expressing MHC-II+, CD80+ and CD86+ molecules was significantly increased, and interleukin-12 and interferon-γ levels were significantly higher in the supernatants when
Prates, D. B.; Jardim, C. L. T. F.; Ferreira, L. A. F.; da Silva, J. M.; Kritz, M. V.
Epidemics are an extremely important matter of study within the Mathematical Modeling area and can be widely found in the literature. Some epidemiological models use differential equations, which are very sensible to parameters, to represent and describe the diseases mathematically. For this work, a variation of the SIR model is discussed and applied to a certain epidemic scenario, wherein vaccination is introduced through two different strategies: constant vaccination and vaccination in pulses. Other epidemiological and population aspects are also considered, such as mortality/natality and infection rates. The analysis and results are performed through numerical solutions of the model and a special attention is given to the discussion generated by the paramenters variation.
Full Text Available In 1988, the World Health Organization (WHO resolved to eradicate poliomyelitis globally. Since then, the initiative has reported dramatic progress in decreasing the incidence of poliomyelitis and limiting the geographical extent of transmission. 2013 is recorded as the second consecutive year not reporting wild poliovirus (WPV from India. If the country can retain this position for one more year India will be declared as polio eradicated. What should be the future vaccination strategies? We searched and reviewed the full text of the available published literature on polio eradication via PubMed and examined Internet sources and websites of major international health agencies. The oral polio vaccine (OPV has been the main tool in the polio eradication program. Once WPV transmission is interrupted, the poliomyelitis will be caused only by OPV. India could expect 1 vaccine-associated paralytic polio per 4.2-4.6 million doses of OPV. Considering the threat of vaccine-derived viruses to polio eradication, WHO urged to develop a strategy to safely discontinue OPV after certification. The ultimate aim is to stop OPV safely and effectively, and eventually substitute with inactivated polio vaccine (IPV. The argument against the use of IPV is its cost. From India, field based data were available on the efficacy of IPV, which was better than OPV. IPV given intradermally resulted in seroconversion rates similar to full-dose intramuscular vaccine. The incremental cost of adopting IPV to replace OPV is relatively low, about US $1 per child per year, and most countries should be able to afford this additional cost.
Kadish, Anna S; Einstein, Mark H
To review novel immunologic strategies for the prevention and treatment of human papillomavirus infection and associated diseases. Both animal model systems and human protocols are discussed. Many vaccine platforms for both prevention of human papillomavirus infection and treatment of associated disease have been developed. Virus-like particle constructs containing human papillomavirus capsid proteins have been shown to protect against human papillomavirus infection. Novel peptide or protein constructs containing modified E6 or E7 proteins, novel adjuvants, fusion proteins such as immunoglobulin-G-heavy chain E7, or heat shock proteins have been made as therapeutic modalities. In addition, many new recombinant vaccine vectors such as vaccinia, Listeria species, adenovirus, Semliki Forest vectors, and others have been developed as carriers of immunotherapeutic agents. Recently, chimeric virus-like particle vaccines have been developed to treat existing human papillomavirus-induced neoplasms. Immunotherapy protocols using a variety of recombinant vectors and modified human papillomavirus proteins induce in-vitro T cell responses and may lead to tumor regression. Vaccine-induced in-vitro immune reactivity and clinical vaccine effects are often not well associated. Further analysis of ongoing human immunotherapy trials is awaited.
Zhong, C; Zhang, L; Chen, L; Deng, L; Li, R
Essentials Coagulation Factor (F) XI is a safe target for the development of antithrombotics. We designed an antigen comprising the human FXI catalytic domain and diphtheria toxin T domain. Antigen immunization reduced plasma FXI activity by 54% and prevented thrombosis in mice. FXI vaccination can serve as an effective strategy for thrombosis prevention. Background Coagulation factor XI serves as a signal amplifier in the intrinsic coagulation pathway. Blockade of FXI by mAbs or small-molecule inhibitors inhibits thrombosis without causing severe bleeding, which is an inherent risk of currently available antithrombotic agents. Objectives To design an FXI vaccine and assess its efficacy in inhibiting FXI activity and preventing thrombosis. Methods An FXI antigen was generated by fusing the catalytic domain of human FXI to the C-terminus of the transmembrane domain of diphtheria toxin. The anti-FXI antibody response, plasma FXI activity and antithrombotic efficacy in mice immunized with the FXI antigen were examined. Results The antigen elicited a significant antibody response against mouse FXI, and reduced the plasma FXI activity by 54.0% in mice. FXI vaccination markedly reduced the levels of coagulation and inflammation in a mouse model of inferior vena cava stenosis. Significant protective effects were also observed in mouse models of venous thrombosis and pulmonary embolism. Conclusions Our data demonstrate that FXI vaccination can serve as an effective strategy for thrombosis prevention. © 2016 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis.
Sohy, Denis; Dusart, Isabelle; Goulet, Philibert; Visy, Diane; Gasthuys, Luc; Poplazarova, Tatjana; Breuer, Thomas; Begg, Norman
Involving patients in the development of medicines and vaccines should result in benefits to patients. The vaccine recipient is usually a healthy person. We describe the rationale and implementation of a vaccine company's initiative to encourage employees to identify with patients of the conditions prevented by the vaccines they help to produce. The Voice of the Patient ("VoP"), begun in 2014, is an educational programme directed at the 16,000 employees of a global vaccine company. It engages employees through an understanding that they are all "vaccine patients", and that they can make a difference by considering the impact of decisions made in their day to day work. The initiative includes presentations about vaccine-preventable diseases, global live webcasts with experts and patients, employee visits to healthcare facilities in developing countries, and the production of patient-focused sections in research publications. In a 2017 employee survey, 90% of respondents said they know how their daily work impacts patients and they demonstrate focus on patients. We believe this is preliminary evidence that, by supporting employee awareness of the impact of their individual roles, VoP could be a model for a type of initiative that will contribute to industry's continuing evolution towards more patient-centred healthcare.
Oku, Afiong; Oyo-Ita, Angela; Glenton, Claire; Fretheim, Atle; Ames, Heather; Muloliwa, Artur; Kaufman, Jessica; Hill, Sophie; Cliff, Julie; Cartier, Yuri; Owoaje, Eme; Bosch-Capblanch, Xavier; Rada, Gabriel; Lewin, Simon
Effective vaccination communication with parents is critical in efforts to overcome barriers to childhood vaccination, tackle vaccine hesitancy and improve vaccination coverage. Health workers should be able to provide information to parents and other caregivers and support them in reaching decisions about vaccinating their children. Limited information exists regarding the perceptions of caregivers and health workers on the vaccination communication strategies employed in Nigeria. This study, which forms part of the 'Communicate to vaccinate' (COMMVAC) project, aims to explore the perceptions and experiences of caregivers and health workers in Nigeria on vaccination communication strategies implemented in their settings. We conducted the study in two States: Bauchi in Northern Nigeria and Cross River in the south. We carried out observations (n = 40), in-depth interviews (n = 14) and focus group discussions (FGDs) (n = 12) amongst 14 purposively selected health workers, two community leaders and 84 caregivers in the two states. We transcribed data verbatim and analysed the data using a framework analysis approach. Caregivers were informed about vaccination activities through three main sources: health facilities (during health education sessions conducted at antenatal or immunization clinics); media outlets; and announcements (in churches/mosques, communities and markets). Caregivers reported that the information received was very useful. Their preferred sources of information included phone text messages, town announcers, media and church/mosque announcements. Some caregivers perceived the clinic environment, long waiting times and health worker attitudes as barriers to receiving vaccination information.When delivering communication interventions, health workers described issues tied to poor communication skills; poor motivation; and attitudes of community members, including vaccine resistance. Communication about vaccination involves more than the message but is
Full Text Available Effective vaccination communication with parents is critical in efforts to overcome barriers to childhood vaccination, tackle vaccine hesitancy and improve vaccination coverage. Health workers should be able to provide information to parents and other caregivers and support them in reaching decisions about vaccinating their children. Limited information exists regarding the perceptions of caregivers and health workers on the vaccination communication strategies employed in Nigeria. This study, which forms part of the 'Communicate to vaccinate' (COMMVAC project, aims to explore the perceptions and experiences of caregivers and health workers in Nigeria on vaccination communication strategies implemented in their settings.We conducted the study in two States: Bauchi in Northern Nigeria and Cross River in the south. We carried out observations (n = 40, in-depth interviews (n = 14 and focus group discussions (FGDs (n = 12 amongst 14 purposively selected health workers, two community leaders and 84 caregivers in the two states. We transcribed data verbatim and analysed the data using a framework analysis approach.Caregivers were informed about vaccination activities through three main sources: health facilities (during health education sessions conducted at antenatal or immunization clinics; media outlets; and announcements (in churches/mosques, communities and markets. Caregivers reported that the information received was very useful. Their preferred sources of information included phone text messages, town announcers, media and church/mosque announcements. Some caregivers perceived the clinic environment, long waiting times and health worker attitudes as barriers to receiving vaccination information.When delivering communication interventions, health workers described issues tied to poor communication skills; poor motivation; and attitudes of community members, including vaccine resistance.Communication about vaccination involves more than the
Peek, H W; Landman, W J M
Coccidiosis in chickens is a parasitic disease with great economic significance, which has been controlled successfully for decades using mainly anticoccidial products. However, large-scale and long-term use of anticoccidial drugs has led to the worldwide development of resistance against all these drugs. In order to minimize the occurrence of resistance, the rotation of various anticoccidial drugs in single and/or shuttle programmes is used. Unfortunately, this has not solved the anticoccidial resistance problem. Recently, live anticoccidial vaccines have been incorporated into rotation programmes, resulting in an increasing incidence of anticoccidial drug-sensitive Eimeria spp. field isolates, which may ameliorate the efficacy of anticoccidial drugs. Nevertheless, possible upcoming bans restricting the use of anticoccidials as feed additives, consumer concerns on residues and increasing regulations have prompted the quest for alternative coccidiosis control strategies. Although management and biosecurity measures could halt the introduction of Eimeria spp. to a farm, in practice they do not suffice to prevent coccidiosis outbreaks. Phytotherapy, aromatherapy and pre- and probiotics either show conflicting, non-consistent or non-convincing results, and have therefore not been applied at a large scale in the field. So far, live attenuated and non-attenuated anticoccidial vaccines have proved to be the most solid and successful coccidiosis prevention and control strategy. Despite the drawbacks associated with their production and use, their popularity is increasing. If with time, the immunogenicity of subunit vaccines can be improved, they could represent the next generation of highly efficient and low-cost anticoccidial strategies.
Full Text Available People's inability to update their memories in light of corrective information may have important public health consequences, as in the case of vaccination choice. In the present study, we compare three potentially effective strategies in vaccine promotion: one contrasting myths vs. facts, one employing fact and icon boxes, and one showing images of non-vaccinated sick children. Beliefs in the autism/vaccines link and in vaccines side effects, along with intention to vaccinate a future child, were evaluated both immediately after the correction intervention and after a 7-day delay to reveal possible backfire effects. Results show that existing strategies to correct vaccine misinformation are ineffective and often backfire, resulting in the unintended opposite effect, reinforcing ill-founded beliefs about vaccination and reducing intentions to vaccinate. The implications for research on vaccines misinformation and recommendations for progress are discussed.
Salari, Raziye; Backman, Anna
: For parenting programs to achieve a public health impact, it is necessary to develop more effective marketing strategies to increase public awareness of these programs and promote parental participation. In this article, we compared a promotion-focused and a prevention-focused strategy via two studies. : We designed two ads inviting parents to participate in a universal parenting program; one ad focused on the program increasing the likelihood of positive outcomes for children (promotion-focused) and the other on the program reducing the likelihood of negative outcomes (prevention-focused). In study I, the two ads were run online simultaneously. Those who clicked on an ad were directed to a website where they could read about and sign up for the program. In study II, a community sample of 706 parents answered a questionnaire about the ads. : In study I, over 85 days, the prevention ad generated more clicks. There was no difference in the number of pages visited on the website nor in the number of parents who signed up for the program. In study II, parents showed a preference for the promotion ad, perceiving it as more relevant and rating it as more effective in getting them interested in the program. : A prevention strategy may be more effective in drawing public attention, in general. However, a promotion strategy is more likely to reach parents, in particular, and inspire them to consider participating in parenting programs. These strategies should be developed further and tested in both general and clinical populations.
Full Text Available The development of diagnostic tests which can readily differentiate between vaccinated and tuberculosis-infected individuals is crucial for the wider utilization of bacillus Calmette-Guérin (BCG as vaccine in humans and animals. BCG_0092 is an antigen that elicits specific delayed type hypersensitivity reactions similar in size and morphological aspects to that elicited by purified protein derivative, in both animals and humans infected with the tubercle bacilli. We carried out bioinformatics analyses of the BCG_0092 and designed a diagnostic test by using the predicted MHC class I epitopes. In addition, we performed a knockout of this gene by homologous recombination in the BCG vaccine strain to allow differentiation of vaccinated from infected individuals. For that, the flanking sequences of the target gene (BCG_0092were cloned into a suicide vector. Spontaneous double crossovers, which result in wild type revertants or knockouts were selected using SacB. BCG_0092 is present only in members of the Mycobacterium tuberculosis complex. Eight predicted MHC class I epitopes with potential for immunological diagnosis were defined, allowing the design of a specific diagnostic test. The strategy used to delete the (BCG_0092 gene from BCG was successful. The knockout genotype was confirmed by PCR and by Southern blot. The mutant BCG strain has the potential of inducing protection against tuberculosis without interfering with the diagnostic test based on the use of selected epitopes from BCG_0092.
Oyo-Ita, Angela; Glenton, Claire; Fretheim, Atle; Ames, Heather; Muloliwa, Artur; Kaufman, Jessica; Hill, Sophie; Cliff, Julie; Cartier, Yuri; Owoaje, Eme; Bosch-Capblanch, Xavier; Rada, Gabriel; Lewin, Simon
Background Effective vaccination communication with parents is critical in efforts to overcome barriers to childhood vaccination, tackle vaccine hesitancy and improve vaccination coverage. Health workers should be able to provide information to parents and other caregivers and support them in reaching decisions about vaccinating their children. Limited information exists regarding the perceptions of caregivers and health workers on the vaccination communication strategies employed in Nigeria. This study, which forms part of the ‘Communicate to vaccinate’ (COMMVAC) project, aims to explore the perceptions and experiences of caregivers and health workers in Nigeria on vaccination communication strategies implemented in their settings. Methodology We conducted the study in two States: Bauchi in Northern Nigeria and Cross River in the south. We carried out observations (n = 40), in-depth interviews (n = 14) and focus group discussions (FGDs) (n = 12) amongst 14 purposively selected health workers, two community leaders and 84 caregivers in the two states. We transcribed data verbatim and analysed the data using a framework analysis approach. Results Caregivers were informed about vaccination activities through three main sources: health facilities (during health education sessions conducted at antenatal or immunization clinics); media outlets; and announcements (in churches/mosques, communities and markets). Caregivers reported that the information received was very useful. Their preferred sources of information included phone text messages, town announcers, media and church/mosque announcements. Some caregivers perceived the clinic environment, long waiting times and health worker attitudes as barriers to receiving vaccination information.When delivering communication interventions, health workers described issues tied to poor communication skills; poor motivation; and attitudes of community members, including vaccine resistance. Conclusion Communication about
Full Text Available Multiple observations in preclinical and clinical studies support a role for the immune system in controlling tumor growth and progression. Various components of the innate and adaptive immune response are able to mediate tumor cell destruction; however, certain immune cell populations can also induce a protumor environment that favors tumor growth and the development of metastasis. Moreover, tumor cells themselves are equipped with various mechanisms that allow them to evade surveillance by the immune system. The goal of cancer vaccines is to induce a tumor-specific immune response that ultimately will reduce tumor burden by tipping the balance from a protumor to an antitumor immune environment. This review discusses common mechanisms that govern immune cell activation and tumor immune escape, and some of the current strategies employed in the field of cancer vaccines aimed at enhancing activation of tumor-specific T-cells with concurrent reduction of immunosuppression.
Lee, Donghoon; Park, Sang Min
To tackle the high prevalence of Hepatitis B virus (HBV) infection in North Korea, it is essential that birth doses of HBV vaccines should be administered within 24 hours of birth. As the country fails to provide a Timely Birth Dose (TBD) of HBV vaccine, the efforts of reducing the high prevalence of HBV have been significantly hampered. To examine the cost-effectiveness of vaccination strategies to prevent perinatal transmission of HBV in North Korea, we established a decision tree with a Markov model consisting of selective, universal, and the country's current vaccination program against HBV. The cost-effectiveness analysis was performed from societal and payer's perspectives and evaluated by Disability Adjusted Life Year (DALY). The results suggest that introducing the universal vaccination would prevent 1,866 cases of perinatal infections per 100,000 of the birth cohort of 2013. Furthermore, 900 cases of perinatal infections per 100,000 could be additionally averted if switching to the selective vaccination. The current vaccination is a dominated strategy both from the societal and payer's perspective. The Incremental Cost-Effectiveness Ratio (ICER) between universal and selective vaccination is $267 from the societal perspective and is reported as $273 from the payer's perspective. Based on the assumption that the 2012 Gross Domestic Product (GDP) per capita in North Korea, $582.6 was set for cost-effectiveness criteria, the result of this study indicates that selective vaccination may be a highly cost-effective strategy compared to universal vaccination.
V. T. Devine
Full Text Available Seven-valent pneumococcal conjugate vaccine (PCV7 was included in the UK national immunisation program in 2006, and this was replaced by thirteen-valent PCV in 2010. During this time, the carriage of vaccine-type Streptococcus pneumoniae decreased but pneumococcal carriage remained stable due to increases in non-vaccine-type S. pneumoniae. Carriage studies have been undertaken in various countries to monitor vaccine-type replacement and to help predict the serotypes, which may cause invasive disease. There has been less focus on how conjugate vaccines indirectly affect colonization of other nasopharyngeal bacteria. If the nasopharynx is treated as a niche, then bacterial dynamics are accepted to occur. Alterations in these dynamics have been shown due to seasonal changes, antibiotic use, and sibling/day care interaction. It has been shown that, following PCV7 introduction, an eradication of pneumococcal vaccine types has resulted in increases in the abundance of other respiratory pathogens including Haemophilus influenzae and Staphylococcus aureus. These changes are difficult to attribute to PCV7 introduction alone and these studies do not account for further changes due to PCV13 implementation. This review aims to describe nasopharyngeal cocarriage of respiratory pathogens in the PCV era.
Francis, Shelley A; Katz, Mira L
Worldwide, cervical cancer is one of the leading causes of morbidity and mortality among women. Even though women in developing countries account for approximately 85 % of the cervical cancer cases and deaths, disparities in cervical cancer rates are also documented in developed countries like the United States (U.S.). Recently, formative research conducted in the U.S. and developing countries like South Africa have sought to gain a better understanding of the knowledge, beliefs, and attitudes about cervical cancer prevention, HPV, and the acceptance of the HPV vaccine. This study compares findings from two independent focus group studies. One study was conducted in a segregated township in Johannesburg, South Africa (n = 24) and the other study was conducted in Ohio Appalachia (n = 19). The following seven themes emerged during the discussions from both studies: HPV and cervical cancer; health decision making; parent-child communication; healthy children; HPV vaccine costs; sexual abuse; and HPV vaccine education. Findings from both studies indicate the importance of the role of mothers and grandmothers in the health care decision-making process for children and a lack of awareness of HPV and its association with cervical cancer. While there was interest in the HPV vaccine, participants voiced concern about the vaccine's cost and side effects. Some participants expressed concern that receipt of the HPV vaccine may initiate adolescent sexual behavior. However, other participants suggested that the HPV vaccine may protect young women who may experience sexual abuse. The importance of developing culturally appropriate educational materials and programs about cervical cancer prevention and the HPV vaccine were expressed by participants in both countries.
Cartmell, Kathleen B; Young-Pierce, Jennifer; McGue, Shannon; Alberg, Anthony J; Luque, John S; Zubizarreta, Maria; Brandt, Heather M
The objective was to investigate how state level strategies in South Carolina could maximize HPV vaccine uptake. An environmental scan identified barriers, facilitators, and strategies for improving HPV vaccination in South Carolina. Interviews were conducted with state leaders from relevant organizations such as public health agencies, medical associations, K-12 schools, universities, insurers, and cancer advocacy organizations. A thematic content analysis design was used. Digital interview files were transcribed, a data dictionary was created and data were coded using the data dictionary. Thirty four interviews were conducted with state leaders. Barriers to HPV vaccination included lack of HPV awareness, lack of provider recommendation, HPV vaccine concerns, lack of access and practice-level barriers. Facilitators included momentum for improving HPV vaccination, school-entry Tdap requirement, pharmacy-based HPV vaccination, state immunization registry, HEDIS measures and HPV vaccine funding. Strategies for improving HPV vaccination fell into three categories: 1) addressing lack of awareness about the importance of HPV vaccination among the public and providers; 2) advocating for policy changes around HPV vaccine coverage, vaccine education, and pharmacy-based vaccination; and 3) coordination of efforts. A statewide environmental scan generated a blueprint for action to be used to improve HPV vaccination in the state. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.
In this thesis, novel vaccination strategies and targets against Lyme borreliosis are explored, including tick antigens as vaccine targets and the use of DNA vaccination against Borrelia afzelii. Furthermore, Borrelia miyamotoi, a novel tick-borne pathogen is investigated: The presence of Borrelia
Irene A. Harmsen
Full Text Available In recent years, parents have become more disparaging towards childhood vaccination. One group that is critical about the National Immunization Program (NIP and participates less comprises parents with an anthroposophical worldview. Despite the fact that various studies have identified anthroposophists as critical parents with lower vaccination coverage, no research has been done to explore the beliefs underlying their childhood vaccination decision-making. We conducted a qualitative study using three focus groups ( of parents who visit an anthroposophical child welfare center. Our findings show that participants did not refuse all vaccinations within the Dutch NIP, but mostly refused the Mumps, Measles, and Rubella (MMR vaccination. Vaccination decisions are influenced by participants’ lifestyle, perception of health, beliefs about childhood diseases, perceptions about the risks of diseases, perceptions about vaccine effectiveness and vaccine components, and trust in institutions. Parents indicated that they felt a need for more information. Sufficient references should be provided to sources containing more information about childhood vaccination, especially about the effectiveness of vaccines and vaccine components and the risks, such as possible side effects and benefits of vaccination. This may satisfy parents’ information needs and enable them to make a sufficiently informed choice whether or not to vaccinate their child.
de Goede, A L; Vulto, A G; Osterhaus, A D M E; Gruters, R A
HIV infection leads to a gradual loss CD4(+) T lymphocytes comprising immune competence and progression to AIDS. Effective treatment with combined antiretroviral drugs (cART) decreases viral load below detectable levels but is not able to eliminate the virus from the body. The success of cART is frustrated by the requirement of expensive lifelong adherence, accumulating drug toxicities and chronic immune activation resulting in increased risk of several non-AIDS disorders, even when viral replication is suppressed. Therefore, there is a strong need for therapeutic strategies as an alternative to cART. Immunotherapy, or therapeutic vaccination, aims to increase existing immune responses against HIV or induce de novo immune responses. These immune responses should provide a functional cure by controlling viral replication and preventing disease progression in the absence of cART. The key difficulty in the development of an HIV vaccine is our ignorance of the immune responses that control of viral replication, and thus how these responses can be elicited and how they can be monitored. Part one of this review provides an extensive overview of the (patho-) physiology of HIV infection. It describes the structure and replication cycle of HIV, the epidemiology and pathogenesis of HIV infection and the innate and adaptive immune responses against HIV. Part two of this review discusses therapeutic options for HIV. Prevention modalities and antiretroviral therapy are briefly touched upon, after which an extensive overview on vaccination strategies for HIV is provided, including the choice of immunogens and delivery strategies. Copyright © 2014. Published by Elsevier Masson SAS.
Skeate, Joseph G.; Woodham, Andrew W.; Einstein, Mark H.; Da Silva, Diane M.; Kast, W. Martin
ABSTRACT Carcinomas of the anogenital tract, in particular cervical cancer, remains one of the most common cancers in women, and represent the most frequent gynecological malignancies and the fourth leading cause of cancer death in women worldwide. Human papillomavirus (HPV)-induced lesions are immunologically distinct in that they express viral antigens, which are necessary to maintain the cancerous phenotype. The causal relationship between HPV infection and anogenital cancer has prompted substantial interest in the development of therapeutic vaccines against high-risk HPV types targeting the viral oncoproteins E6 and E7. This review will focus on the most recent clinical trials for immunotherapies for mucosal HPV-induced lesions as well as emerging therapeutic strategies that have been tested in pre-clinical models for HPV-induced diseases. Progress in peptide- and protein-based vaccines, DNA-based vaccines, viral/bacterial vector-based vaccines, immune checkpoint inhibition, immune response modifiers, and adoptive cell therapy for HPV will be discussed. PMID:26835746
of any other age group, perhaps highlighting the vulnerability of the elderly due to close contacts with their caretakers from other age groups. The relative impact of targeting the very young and the very old for vaccination was weakened by their relative inactivity, thus giving evidence of the lack of impact of vaccinating these two groups on the overall transmissibility of the disease in the community. This further underscores the need for morbidity-based strategy to prevent elderly mortality.
In Nigeria infectious bursal disease (IBD) outbreaks have persisted despite routine vaccination. In a quest to determine some of the causes of the vaccination failures, the type of vaccines, vaccination schedules and seromonitoring for antibodies in breeder and commercial farms were investigated using structured ...
Wiser, Itay; Balicer, Ran D; Cohen, Dani
The threat of using variola virus in a bioterrorist attack urged different countries to renew the production of traditional vaccines and develop new generations of smallpox vaccines. Manufacturers try to combine smallpox vaccine past experience with technological advances in vaccine development to achieve protection similar to that of the traditional vaccines with a higher level of safety and fewer contraindications. In light of the reported immunogenicity and reactogenicity of the stockpiled smallpox vaccines employed in the last immunization campaigns of "first responders", we review recently accumulated data on the assessment of new smallpox vaccine candidates and discuss their role in possible vaccination policies.
Lee, Donghoon; Park, Sang Min
.... Methods To examine the cost-effectiveness of vaccination strategies to prevent perinatal transmission of HBV in North Korea, we established a decision tree with a Markov model consisting of selective...
de la Fuente, J; Kopáček, P; Lew-Tabor, A; Maritz-Olivier, C
Ticks infest a variety of animal species and transmit pathogens causing disease in both humans and animals worldwide. Tick-host-pathogen interactions have evolved through dynamic processes that accommodated the genetic traits of the hosts, pathogens transmitted and the vector tick species that mediate their development and survival. New approaches for tick control are dependent on defining molecular interactions between hosts, ticks and pathogens to allow for discovery of key molecules that could be tested in vaccines or new generation therapeutics for intervention of tick-pathogen cycles. Currently, tick vaccines constitute an effective and environmentally sound approach for the control of ticks and the transmission of the associated tick-borne diseases. New candidate protective antigens will most likely be identified by focusing on proteins with relevant biological function in the feeding, reproduction, development, immune response, subversion of host immunity of the tick vector and/or molecules vital for pathogen infection and transmission. This review addresses different approaches and strategies used for the discovery of protective antigens, including focusing on relevant tick biological functions and proteins, reverse genetics, vaccinomics and tick protein evolution and interactomics. New and improved tick vaccines will most likely contain multiple antigens to control tick infestations and pathogen infection and transmission. © 2016 John Wiley & Sons Ltd.
Adeliane C da Costa
Full Text Available BCG (Bacille Calmette-Guérin, an attenuated vaccine derived from Mycobacterium bovis, is the current vaccine of choice against tuberculosis (TB. Despite its protection against active TB in children, BCG has failed to protect adults against TB infection and active disease development, especially in developing countries where the disease is endemic. Currently, there is a significant effort towards the development of a new TB vaccine. This review article aims to address publications on recombinant BCG (rBCG published in the last 5 years, to highlight the strategies used to develop rBCG, with a focus on the criteria used to improve immunological memory and protection compared with BCG. The literature review was done in April 2013, using the key words tuberculosis, rBCG vaccine and memory. This review discusses the BCG strains and strategies currently used for the modification of BCG, including: overexpression of M. tuberculosis (Mtb immunodominant antigens already present in BCG; gene insertion of immunodominant antigens from Mtb absent in the BCG vaccine; combination of introduction and over expression of genes that are lost during the attenuation process of BCG; BCG modifications for the induction of CD8+ T cell immune responses and cytokines expressing rBCG. Among the vaccines discussed, VPM1002, also called rBCGΔureC::hly, is currently in human clinical trials. Much progress has been made in the effort to improve BCG, with some promising candidates, but considerable work is still required to address functional long-lasting memory.
Ford, Carol A; English, Abigail; Davenport, Amy F; Stinnett, Amy J
To increase understanding of the policy, legal, and financial issues influencing efforts to achieve high rates of adolescent vaccination. We conducted semistructured telephone interviews with 49 key informants in nine states, five jurisdictions, and at the national level. We elicited: (a) experiences with human papillomavirus (HPV) and meningococcal vaccine programs; (b) perspectives on policy, legal, and financing issues influencing adolescent vaccine program effectiveness; and (c) strategies to increase rates of adolescent vaccination. Common and informative themes were identified by content analyses. Participants reported that barriers to adolescent vaccination included: public concerns (insufficient knowledge, negative attitudes, safety concerns, controversy); practitioner concerns (insufficient knowledge or ambivalence about recommendations); delivery issues (insufficient access to or use of healthcare, vaccines not at healthcare site or part of routine care); minor consent issues; cost/financing issues; and lack of coordination in timing of vaccine recommendations, supply, and financing. Many barriers and promising strategies for overcoming them vary depending on adolescent age. For example, concerns about providing vaccines to prevent sexually transmitted diseases are less frequent with respect to older adolescents; issues of consent vary widely between 11 and 25 years of age; and financial barriers/potential solutions vary by age. We develop a framework to address policy, legal, and financial issues influencing adolescent vaccination based on adolescent age. A comprehensive description of factors influencing adolescent vaccination reveals variation based on age. A framework that incorporates this complexity may enhance strategies to increase rates of vaccine delivery to adolescent populations.
Wardle, Jon; Stewart, Cameron; Parker, Malcolm
Misleading vaccination information undermines confidence in vaccination and may lead to reductions in the effectiveness of vaccination programs. A number of regulatory techniques can be employed to challenge the spread of false information, including health care complaints, therapeutic goods laws, consumer protection laws and professional discipline. This article examines three case studies involving the publication of anti-vaccination information by non-professionally aligned organisations, by non-registered health professionals, and by registered health professionals under the National Law. The article examines the effectiveness of different regulatory responses and makes suggestions for future strategies to deal with the publication of demonstrably false information regarding vaccination.
Full Text Available An editorial perspective on Barbieri and Capri article: Is vaccination good value for money? A review of cost-utility analyses of vaccination strategies in eight European countries
Korber, Bette [Los Alamos National Laboratory
HIV's rapid global spread and the human suffering it has left in its wake have made AIDS a global heath priority for the 25 years since its discovery. Yet its capacity to rapidly evolve has made combating this virus a tremendous challenge. The obstacles to creating an effective HIV vaccine are formidable, but there are advances in the field on many fronts, in terms of novel vectors, adjuvants, and antigen design strategies. SIV live attenuated vaccine models are able to confer protection against heterologous challenge, and this continues to provide opportunities to explore the biological underpinnings of a protective effect (9). More indirect, but equally important, is new understanding regarding the biology of acute infection (43), the role of immune response in long-term non-progression (6,62, 81), and defining characteristics of broadly neutralizing antibodies (4). In this review we will focus on summarizing strategies directed towards a single issue, that of contending with HIV variation in terms of designing aT-cell vaccine. The strategies that prove most effective in this area can ultimately be combined with the best strategies under development in other areas, with the hope of ultimately converging on a viable vaccine candidate. Only two large HIV vaccine efficacy trials have been completed and both have failed to prevent infection or confer a benefit to infected individual (23,34), but there is ample reason to continue our efforts. A historic breakthrough came in 1996, when it was realized that although the virus could escape from a single antiretroviral (ARV) therapy, it could be thwarted by a combination of medications that simultaneously targeted different parts of the virus (HAART) (38). This revelation came after 15 years of research, thought, and clinical testing; to enable that vital progress the research and clinical communities had to first define and understand, then develop a strategy to counter, the remarkable evolutionary potential of the
Full Text Available To tackle the high prevalence of Hepatitis B virus (HBV infection in North Korea, it is essential that birth doses of HBV vaccines should be administered within 24 hours of birth. As the country fails to provide a Timely Birth Dose (TBD of HBV vaccine, the efforts of reducing the high prevalence of HBV have been significantly hampered.To examine the cost-effectiveness of vaccination strategies to prevent perinatal transmission of HBV in North Korea, we established a decision tree with a Markov model consisting of selective, universal, and the country's current vaccination program against HBV. The cost-effectiveness analysis was performed from societal and payer's perspectives and evaluated by Disability Adjusted Life Year (DALY.The results suggest that introducing the universal vaccination would prevent 1,866 cases of perinatal infections per 100,000 of the birth cohort of 2013. Furthermore, 900 cases of perinatal infections per 100,000 could be additionally averted if switching to the selective vaccination. The current vaccination is a dominated strategy both from the societal and payer's perspective. The Incremental Cost-Effectiveness Ratio (ICER between universal and selective vaccination is $267 from the societal perspective and is reported as $273 from the payer's perspective.Based on the assumption that the 2012 Gross Domestic Product (GDP per capita in North Korea, $582.6 was set for cost-effectiveness criteria, the result of this study indicates that selective vaccination may be a highly cost-effective strategy compared to universal vaccination.
Soema, Peter C; Kompier, Ronald; Amorij, Jean-Pierre; Kersten, Gideon F A
Vaccination is the most effective method to prevent influenza infection. However, current influenza vaccines have several limitations. Relatively long production times, limited vaccine capacity, moderate efficacy in certain populations and lack of cross-reactivity are important issues that need to be addressed. We give an overview of the current status and novel developments in the landscape of influenza vaccines from an interdisciplinary point of view. The feasibility of novel vaccine concepts not only depends on immunological or clinical outcomes, but also depends on biotechnological aspects, such as formulation and production methods, which are frequently overlooked. Furthermore, the next generation of influenza vaccines is addressed, which hopefully will bring cross-reactive influenza vaccines. These developments indicate that an exciting future lies ahead in the influenza vaccine field. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.
Rashmirani Senapati; Bhagyalaxmi Nayak; Shantanu Kumar Kar; Bhagirathi Dwibedi
HPV is the major causative agent for cervical cancer. Study on the risk of cervical cancer associated with different hr-HPV genotypes would be useful for disease management and new vaccine strategy...
Mena, Guillermo; Llupi?, Anna; Garc?a-Basteiro, Alberto L; Sequera, Victor-Guillermo; Aldea, Marta; Bayas, Jos? Mar?a; Trilla, Antoni
Background Influenza vaccination coverage in medical students is usually low. Unlike health care workers, there is little information on the attitudes to and predictors of vaccination among medical students, and their attitudes towards institutional strategies for improving rates are unknown. Methods This cross-sectional study evaluated the effect of three influenza vaccination promotional strategies (Web page, video and tri-fold brochure) on medical students? intention to get vaccinated and ...
Soema, P.C.; Kompier, R.; Amorij, J.P.; Kersten, G.F.A.
Vaccination is the most effective method to prevent influenza infection. However, current influenza vaccines have several limitations. Relatively long production times, limited vaccine capacity, moderate efficacy in certain populations and lack of cross-reactivity are important issues that need to
Pach, Alfred; Tabbusam, Ghurnata; Khan, M Imran; Suhag, Zamir; Hussain, Imtiaz; Hussain, Ejaz; Mumtaz, Uzma; Haq, Inam Ul; Tahir, Rehman; Mirani, Amjad; Yousafzai, Aisha; Sahastrabuddhe, Sushant; Ochiai, R Leon; Soofi, Sajid; Clemens, John D; Favorov, Michael O; Bhutta, Zulfiqar A
The authors conducted formative research (a) to identify stakeholders' concerns related to typhoid fever and the need for disease information and (b) to develop a communication strategy to inform stakeholders and address their concerns and motivate for support of a school-based vaccination program in Pakistan. Data were collected during interactive and semi-structured focus group discussions and interviews, followed by a qualitative analysis and multidisciplinary consultative process to identify an effective social mobilization strategy comprised of relevant media channels and messages. The authors conducted 14 focus group discussions with the parents of school-aged children and their teachers, and 13 individual interviews with school, religious, and political leaders. Parents thought that typhoid fever was a dangerous disease, but were unsure of their children's risk. They were interested in vaccination and were comfortable with a school-based vaccination if conducted under the supervision of trained and qualified staff. Teachers and leaders needed information on typhoid fever, the vaccine, procedures, and sponsors of the vaccination program. Meetings were considered the best form of information dissemination, followed by printed materials and mass media. This study shows how qualitative research findings can be translated into an effective social mobilization and communication approach. The findings of the research indicated the importance of increasing awareness of typhoid fever and the benefits of vaccination against the disease. Identification and dissemination of relevant, community-based disease and vaccination information will increase demand and use of vaccination.
Ulrich E. Schaible
Full Text Available The global tuberculosis epidemic is the most common cause of death after infectious disease worldwide. Increasing numbers of infections with multi- and extensively drug-resistant variants of the Mycobacterium tuberculosis complex, resistant even to newly discovered and last resort antibiotics, highlight the urgent need for an efficient vaccine. The protective efficacy to pulmonary tuberculosis in adults of the only currently available vaccine, M. bovis BCG, is unsatisfactory and geographically diverse. More importantly, recent clinical studies on new vaccine candidates did not prove to be better than BCG, yet. Here, we propose and discuss novel strategies to improve efficacy of existing anti-tuberculosis vaccines. Modulation of innate immune responses upon vaccination already provided promising results in animal models of tuberculosis. For instance, neutrophils have been shown to influence vaccine efficacy, both, positively and negatively, and stimulate specific antibody secretion. Modulating immune regulatory properties after vaccination such as induction of different types of innate immune cell death, myeloid-derived suppressor or regulatory T cells, production of anti-inflammatory cytokines such as IL-10 may have beneficial effects on protection efficacy. Incorporation of lipid antigens presented via CD1 molecules to T cells have been discussed as a way to enhance vaccine efficacy. Finally, concepts of dendritic cell-based immunotherapies or training the innate immune memory may be exploitable for future vaccination strategies against tuberculosis. In this review, we put a spotlight on host immune networks as potential targets to boost protection by old and new tuberculosis vaccines.
Kumru, Ozan S; Joshi, Sangeeta B; Smith, Dawn E; Middaugh, C Russell; Prusik, Ted; Volkin, David B
Instability of vaccines often emerges as a key challenge during clinical development (lab to clinic) as well as commercial distribution (factory to patient). To yield stable, efficacious vaccine dosage forms for human use, successful formulation strategies must address a combination of interrelated topics including stabilization of antigens, selection of appropriate adjuvants, and development of stability-indicating analytical methods. This review covers key concepts in understanding the causes and mechanisms of vaccine instability including (1) the complex and delicate nature of antigen structures (e.g., viruses, proteins, carbohydrates, protein-carbohydrate conjugates, etc.), (2) use of adjuvants to further enhance immune responses, (3) development of physicochemical and biological assays to assess vaccine integrity and potency, and (4) stabilization strategies to protect vaccine antigens and adjuvants (and their interactions) during storage. Despite these challenges, vaccines can usually be sufficiently stabilized for use as medicines through a combination of formulation approaches combined with maintenance of an efficient cold chain (manufacturing, distribution, storage and administration). Several illustrative case studies are described regarding mechanisms of vaccine instability along with formulation approaches for stabilization within the vaccine cold chain. These include live, attenuated (measles, polio) and inactivated (influenza, polio) viral vaccines as well as recombinant protein (hepatitis B) vaccines. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.
Kaare, M.; Lembo, T.; Hampson, K.; Ernest, E.; Estes, A.; Mentzel, C.; Cleaveland, S.
Effective vaccination campaigns need to reach a sufficient percentage of the population to eliminate disease and prevent future outbreaks, which for rabies is predicted to be 70%, at a cost that is economically and logistically sustainable. Domestic dog rabies has been increasing across most of sub-Saharan Africa indicating that dog vaccination programmes to date have been inadequate. We compare the effectiveness of a variety of dog vaccination strategies in terms of their cost and coverage in different community settings in rural Tanzania. Central-point (CP) vaccination was extremely effective in agro-pastoralist communities achieving a high coverage (>80%) at a low cost (vaccination was costly (>US$5/dog) and inadequate (vaccination or trained community-based animal health workers were most effective with coverage exceeding 70%, although costs were still high (>US$6 and >US$4/dog, respectively). No single vaccination strategy is likely to be effective in all populations and therefore alternative approaches must be deployed under different settings. CP vaccination is cost-effective and efficient for the majority of dog populations in rural Tanzania and potentially elsewhere in sub-Saharan Africa, whereas a combination strategy is necessary in remote pastoralist communities. These results suggest that rabies control is logistically feasible across most of the developing world and that the annual costs of effective vaccination campaigns in Tanzania are likely to be affordable. PMID:18848595
Longini, Ira M; Halloran, M Elizabeth
Despite evidence that vaccinating schoolchildren against influenza is effective in limiting community-level transmission, the United States has had a long-standing government strategy of recommending that vaccine be concentrated primarily in high-risk groups and distributed to those people who keep the health system and social infrastructure operating. Because of this year's influenza vaccine shortage, a plan was enacted to distribute the limited vaccine stock to these groups first. This vaccination strategy, based on direct protection of those most at risk, has not been very effective in reducing influenza morbidity and mortality. Although it is too late to make changes this year, the current influenza vaccine crisis affords the opportunity to examine an alternative for future years. The alternative plan, supported by mathematical models and influenza field studies, would be to concentrate vaccine in schoolchildren, the population group most responsible for transmission, while also covering the reachable high-risk groups, who would also receive considerable indirect protection. In conjunction with a plan to ensure an adequate vaccine supply, this alternative influenza vaccination strategy would help control interpandemic influenza and be instrumental in preparing for pandemic influenza. The effectiveness of the alternative plan could be assessed through nationwide community studies.
Carina S. Pinheiro
Full Text Available The flatworm Schistosoma mansoni is a blood fluke parasite that causes schistosomiasis, a debilitating disease that occurs throughout the developing world. Current schistosomiasis control strategies are mainly based on chemotherapy, but many researchers believe that the best long-term strategy to control schistosomiasis is through immunization with an antischistosomiasis vaccine combined with drug treatment. Several papers on Schistosoma mansoni vaccine and drug development have been published in the past few years, representing an important field of study. The advent of technologies that allow large-scale studies of genes and proteins had a remarkable impact on the screening of new and potential vaccine candidates in schistosomiasis. In this postgenomic scenario, bioinformatic technologies have emerged as important tools to mine transcriptomic, genomic, and proteomic databases. These new perspectives are leading to a new round of rational vaccine development. Herein, we discuss different strategies to identify potential S. mansoni vaccine candidates using computational vaccinology.
Mahoney, Richard T; Krattiger, Anatole; Clemens, John D; Curtiss, Roy
This paper offers a framework for managing a comprehensive Global Access Strategy for new vaccines in developing countries. It is aimed at strengthening the ability of public-sector entities to reach their goals. The Bill and Melinda Gates Foundation and The Rockefeller Foundation have been leaders in stimulating the creation of new organizations - public/private product development partnerships (PDPs) - that seek to accelerate vaccine development and distribution to meet the health needs of the world's poor. Case studies of two of these PDPs - the Salmonella Anti-pneumococcal Vaccine Program and the Pediatric Dengue Vaccine Initiative - examine development of such strategies. Relying on the application of innovation theory, the strategy leads to the identification of six Components of Innovation which cover all aspects of the vaccine innovation process. Appropriately modified, the proposed framework can be applied to the development and introduction of other products in developing countries including drugs, and nutritional and agricultural products.
Full Text Available Joost Dejaegher,1 Stefaan Van Gool,2 Steven De Vleeschouwer1 1Department of Neurosciences, 2Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium Abstract: Glioblastoma multiforme (GBM is the most common and most aggressive type of primary brain cancer. Since median overall survival with multimodal standard therapy is only 15 months, there is a clear need for additional effective and long-lasting treatments. Dendritic cell (DC vaccination is an experimental immunotherapy being tested in several Phase I and Phase II clinical trials. In these trials, safety and feasibility have been proven, and promising clinical results have been reported. On the other hand, it is becoming clear that not every GBM patient will benefit from this highly personalized treatment. Defining the subgroup of patients likely to respond to DC vaccination will position this option correctly amongst other new GBM treatment modalities, and pave the way to incorporation in standard therapy. This review provides an overview of GBM treatment options and focuses on the currently known prognostic and predictive factors for response to DC vaccination. In this way, it will provide the clinician with the theoretical background to refer patients who might benefit from this treatment. Keywords: immunotherapy, personalized medicine, brain tumor, stratification
Dejaegher, Joost; Van Gool, Stefaan; De Vleeschouwer, Steven
Glioblastoma multiforme (GBM) is the most common and most aggressive type of primary brain cancer. Since median overall survival with multimodal standard therapy is only 15 months, there is a clear need for additional effective and long-lasting treatments. Dendritic cell (DC) vaccination is an experimental immunotherapy being tested in several Phase I and Phase II clinical trials. In these trials, safety and feasibility have been proven, and promising clinical results have been reported. On the other hand, it is becoming clear that not every GBM patient will benefit from this highly personalized treatment. Defining the subgroup of patients likely to respond to DC vaccination will position this option correctly amongst other new GBM treatment modalities, and pave the way to incorporation in standard therapy. This review provides an overview of GBM treatment options and focuses on the currently known prognostic and predictive factors for response to DC vaccination. In this way, it will provide the clinician with the theoretical background to refer patients who might benefit from this treatment. PMID:27471700
Friedman, Allison L; Oruko, Kelvin O; Habel, Melissa A; Ford, Jessie; Kinsey, Jennine; Odhiambo, Frank; Phillips-Howard, Penelope A; Wang, Susan A; Collins, Tabu; Laserson, Kayla F; Dunne, Eileen F
Cervical cancer claims the lives of 275,000 women each year; most of these deaths occur in low-or middle-income countries. In Kenya, cervical cancer is the leading cause of cancer-related mortality among women of reproductive age. Kenya's Ministry of Public Health and Sanitation has developed a comprehensive strategy to prevent cervical cancer, which includes plans for vaccinating preteen girls against human papillomavirus (HPV) by 2015. To identify HPV vaccine communication and mobilization needs, this research sought to understand HPV vaccine-related perceptions and concerns of male and female caregivers and community leaders in four rural communities of western Kenya. We conducted five focus groups with caregivers (n = 56) and 12 key-informant interviews with opinion leaders to explore cervical cancer-related knowledge, attitudes and beliefs, as well as acceptability of HPV vaccination for 9-12 year-old girls. Four researchers independently reviewed the data and developed codes based on questions in interview guides and topics that emerged organically, before comparing and reconciling results through a group consensus process. Cervical cancer was not commonly recognized, though it was understood generally in terms of its symptoms. By association with cancer and genital/reproductive organs, cervical cancer was feared and stigmatized. Overall acceptability of a vaccine that prevents cervical cancer was high, so long as it was endorsed by trusted agencies and communities were sensitized first. Some concerns emerged related to vaccine safety (e.g., impact on fertility), program intent, and health equity. For successful vaccine introduction in Kenya, there is a need for communication and mobilization efforts to raise cervical cancer awareness; prompt demand for vaccination; address health equity concerns and stigma; and minimize potential resistance. Visible endorsement by government leaders and community influencers can provide reassurance of the vaccine's safety
Implementation of quality measures, compliance with the Convention on Biological Diversity (CBD), and adoption of latest bioinformatics tools are among the main steps to be taken by microbial culture collections in order to provide resources for the emerging area of the knowledge-based bioeconomy. These measures have to be introduced side by side with the deposition of increasingly phylogenetically and physiologically diverse microbiological organisms. However, the necessary expansion of human resources and infrastructure is moving slowly, if at all. Furthermore, considering that the vast majority of microbial isolates do not find their way into public collections, a strategy should be devised to encourage researchers to deposit a higher fraction of strains. It appears obvious that in order to make available an even broader range of diversity to users and researchers, collections will have to decide whether to diversify on a broad taxon spectrum of the hierarchic system, holding a small number of representatives per species, or to follow the route of focusing on in-depth holdings of selected groups of organisms, depending on existing taxonomic expertise. These decisions require a worldwide coordinated activity with the outcome to be made transparent to users in an emerging global network. Copyright 2010 Elsevier Ltd. All rights reserved.
Full Text Available Bluetongue virus (BTV belongs to the genus Orbivirus within the family Reoviridae. The development of vector-based vaccines expressing conserved protective antigens results in increased immune activation and could reduce the number of multiserotype vaccinations required, therefore providing a cost-effective product. Recent recombinant DNA technology has allowed the development of novel strategies to develop marker and safe vaccines against BTV. We have now engineered naked DNAs and recombinant modified vaccinia virus Ankara (rMVA expressing VP2, VP7 and NS1 proteins from BTV-4. IFNAR((-/- mice inoculated with DNA/rMVA-VP2,-VP7-NS1 in an heterologous prime boost vaccination strategy generated significant levels of antibodies specific of VP2, VP7, and NS1, including those with neutralizing activity against BTV-4. In addition, vaccination stimulated specific CD8(+ T cell responses against these three BTV proteins. Importantly, the vaccine combination expressing NS1, VP2 and VP7 proteins of BTV-4, elicited sterile protection against a lethal dose of homologous BTV-4 infection. Remarkably, the vaccine induced cross-protection against lethal doses of heterologous BTV-8 and BTV-1 suggesting that the DNA/rMVA-VP2,-VP7,-NS1 marker vaccine is a promising multiserotype vaccine against BTV.
Platteel, Anouk C M|info:eu-repo/dai/nl/375805613; Henri, Sandrine; Zaiss, Dietmar M|info:eu-repo/dai/nl/304838381; Sijts, Alice J A M|info:eu-repo/dai/nl/115553843
The skin is an attractive site for vaccination due to its accessibility and presence of immune cells surveilling this barrier. However, knowledge of antigen processing and presentation upon dermal vaccination is sparse. In this study we determined antigen processing routes that lead to CD8(+) T cell
Lambach, Philipp; Alvarez, Alba Maria Ropero; Hirve, Siddhivinayak; Ortiz, Justin R.; Hombach, Joachim; Verweij, Marcel; Hendriks, Jan; Palkonyay, Laszlo; Pfleiderer, Michael
There is potential for influenza vaccine programmes to make a substantial impact on severe disease in low-resource settings, however questions around vaccine composition and programmatic issues will require special attention. Some countries may benefit from immunization programmes that provide
Mirlekar, B; Pathak, S; Pathade, G
Tuberculosis is a major health problem throughout the world causing large number of deaths, more than that from any other single infectious disease. Estimates till date ascertain the fact that Tuberculosis (TB) is continuing to be the leading cause of death worldwide. The infection from single infectious agent Mycobacterium tuberculosis is killing about 3 million individuals every year and accounts for around 18.5% of all deaths in adults between the age group of 15 and 65. An average of 1.79 billion people, which constitutes roughly one-third of the world's population, is infected with the causative agent M. tuberculosis and is at risk of developing the disease. This situation highlights the relative shortcomings of the current treatment and diagnosis strategies for TB and the limited effectiveness of public health systems, particularly in resource-poor countries where the main TB burden lies. The timely identification of persons infected with Mycobacterium tuberculosis and rapid laboratory confirmation of tuberculosis are two key factors for the treatment and prevention of the disease. Novel molecular assays for diagnosis and drug susceptibility testing offer several potential advantages over the above methods including faster turnaround times, very sensitive and specific detection of nucleic acids, and minimal, or possibly no, prior culture. The need for new technologies for rapid diagnosis of tuberculosis is clear. Most studies of mycobacterial immunity attributes focus on proliferation of T cells, production of cytokines and cytolytic activity. A proper vaccine for tuberculosis can be developed by using a combination of antigens and adjuvants capable of inducing appropriate and long-lasting T cell immunity. Development of new vaccines against TB should include some important aspects learned from BCG use such as mucosal routes of immunization; revaccination of BCG immunized subjects, booster immunization and prime-boost strategy with wild-type BCG, and other
Sen, Pritha; Charini, William A; Subbramanian, Ramu A; Manuel, Edwin R; Kuroda, Marcelo J; Autissier, Patrick A; Letvin, Norman L
To afford the greatest possible immune protection, candidate human immunodeficiency virus (HIV) vaccines must generate diverse and long-lasting CD8(+) T lymphocyte responses. In the present study, we evaluate T-cell receptor Vbeta (variable region beta) gene usage and a CDR3 (complementarity-determining region 3) sequence to assess the clonality of epitope-specific CD8(+) T lymphocytes generated in rhesus monkeys following vaccination and simian-human immunodeficiency virus (SHIV) challenge. We found that vaccine-elicited epitope-specific CD8(+) T lymphocytes have a clonal diversity comparable to those cells generated in response to SHIV infection. Moreover, we show that the clonal diversity of vaccine-elicited CD8(+) T-lymphocyte responses is dictated by the epitope sequence and is not affected by the mode of antigen delivery to the immune system. Clonal CD8(+) T-lymphocyte populations persisted following boosting with different vectors, and these clonal cell populations could be detected for as long as 4 years after SHIV challenge. Finally, we show that the breadth of these epitope-specific T lymphocytes transiently focuses in response to intense SHIV replication. These observations demonstrate the importance of the initial immune response to SHIV, induced by vaccination or generated during primary infection, in determining the clonal diversity of cell-mediated immune responses and highlight the focusing of this clonal diversity in the setting of high viral loads. Circumventing this restricted CD8(+) T-lymphocyte clonal diversity may present a significant challenge in the development of an effective HIV vaccine strategy.
Sen, Pritha; Charini, William A.; Subbramanian, Ramu A.; Manuel, Edwin R.; Kuroda, Marcelo J.; Autissier, Patrick A.; Letvin, Norman L.
To afford the greatest possible immune protection, candidate human immunodeficiency virus (HIV) vaccines must generate diverse and long-lasting CD8+ T lymphocyte responses. In the present study, we evaluate T-cell receptor Vβ (variable region beta) gene usage and a CDR3 (complementarity-determining region 3) sequence to assess the clonality of epitope-specific CD8+ T lymphocytes generated in rhesus monkeys following vaccination and simian-human immunodeficiency virus (SHIV) challenge. We found that vaccine-elicited epitope-specific CD8+ T lymphocytes have a clonal diversity comparable to those cells generated in response to SHIV infection. Moreover, we show that the clonal diversity of vaccine-elicited CD8+ T-lymphocyte responses is dictated by the epitope sequence and is not affected by the mode of antigen delivery to the immune system. Clonal CD8+ T-lymphocyte populations persisted following boosting with different vectors, and these clonal cell populations could be detected for as long as 4 years after SHIV challenge. Finally, we show that the breadth of these epitope-specific T lymphocytes transiently focuses in response to intense SHIV replication. These observations demonstrate the importance of the initial immune response to SHIV, induced by vaccination or generated during primary infection, in determining the clonal diversity of cell-mediated immune responses and highlight the focusing of this clonal diversity in the setting of high viral loads. Circumventing this restricted CD8+ T-lymphocyte clonal diversity may present a significant challenge in the development of an effective HIV vaccine strategy. PMID:17977967
da Costa, Adeliane Castro; Nogueira, Sarah Veloso; Kipnis, André; Junqueira-Kipnis, Ana Paula
Bacille Calmette–Guérin (BCG), an attenuated vaccine derived from Mycobacterium bovis, is the current vaccine of choice against tuberculosis (TB). Despite its protection against active TB in children, BCG has failed to protect adults against TB infection and active disease development, especially in developing countries where the disease is endemic. Currently, there is a significant effort toward the development of a new TB vaccine. This review article aims to address publications on recombinant BCG (rBCG) published in the last 5 years, to highlight the strategies used to develop rBCG, with a focus on the criteria used to improve immunological memory and protection compared with BCG. The literature review was done in April 2013, using the key words TB, rBCG vaccine, and memory. This review discusses the BCG strains and strategies currently used for the modification of BCG, including: overexpression of Mycobacterium tuberculosis (Mtb) immunodominant antigens already present in BCG; gene insertion of immunodominant antigens from Mtb absent in the BCG vaccine; combination of introduction and overexpression of genes that are lost during the attenuation process of BCG; BCG modifications for the induction of CD8+ T-cell immune responses and cytokines expressing rBCG. Among the vaccines discussed, VPM1002, also called rBCGΔureC:hly, is currently in human clinical trials. Much progress has been made in the effort to improve BCG, with some promising candidates, but considerable work is still required to address functional long-lasting memory. PMID:24778634
Carlos Rodrigo Zárate-Bladés
Full Text Available In 1882 Robert Koch identified Mycobacterium tuberculosis as the causative agent of tuberculosis (TB, a disease as ancient as humanity. Although there has been more than 125 years of scientific effort aimed at understanding the disease, serious problems in TB persist that contribute to the estimated 1/3 of the world population infected with this pathogen. Nonetheless, during the first decade of the 21st century, there were new advances in the fight against TB. The development of high-throughput technologies is one of the major contributors to this advance, because it allows for a global vision of the biological phenomenon. This paper analyzes how transcriptomics are supporting the translation of basic research into therapies by resolving three key issues in the fight against TB: (a the discovery of biomarkers, (b the explanation of the variability of protection conferred by BCG vaccination, and (c the development of new immunotherapeutic strategies to treat TB.
Full Text Available Usama Assaad,2 Ibrahim El-Masri,2 Jahan Porhomayon,1,3 Ali A El-Solh1–41The Veterans Affairs Western New York Healthcare System, Buffalo, NY, USA; 2Division of Pulmonary, Critical Care, and Sleep Medicine, 3Department of Anesthesia, 4Department of Social and Preventive Medicine, State University of New York at Buffalo School of Medicine and Biomedical Sciences and School of Public Health and Health Professions, Buffalo, NY, USAAbstract: Vaccination remains the primary preventive strategy in the elderly against Streptococcus pneumoniae and influenza infections. The effectiveness of this strategy in preventing pneumonia has been in doubt despite the increase in vaccination coverage among older adults. Randomized controlled trials (RCTs and observational studies aimed at determining clinical outcomes and immune response following pneumococcal vaccination have yielded conflicting results. The protective efficacy of pneumococcal vaccination against pneumonia in older adults has not been firmly established due to a lack of RCTs specifically examining patients ≥ 65 years of age. Similarly, the reported benefits of influenza vaccination have been derived from observational data. The assessment of clinical benefit from influenza vaccination in the elderly population is complicated by varying cohorts, virulence of the influenza strain, and matching of vaccine and circulating viral strains. The presence of selection bias and use of nonspecific end points in these studies make the current evidence inconclusive in terms of overall benefit. The development of more immunogenic vaccines through new formulations or addition of adjuvants holds the promise of revolutionizing delivery and improving efficacy. Dismantling existing barriers through education, providing technology assistance predominantly to developing countries, and establishing clear regulatory guidance on pathways for approval are necessary to ensure timely production and equitable distribution
Andrus, Jon Kim; Sherris, Jacqueline; Fitzsimmons, John W; Kane, Mark A; Aguado, M Teresa
This paper explores different international vaccine financing and procurement strategies used by the Pan American Health Organization, United Nation's Children's Fund, the Global Alliance for Vaccines and Immunization, the Gulf Cooperation Model, and the Advanced Market Commitments. The aim is to identify lessons learned to help ensure equitable distribution of life-saving vaccines for cervical cancer prevention, with particular emphasis on sustainability. A critical first step in the cascade of activities necessary for Human papillomavirus (HPV) vaccine introduction should be the creation of an informed policy decision making process that is grounded in the best available information at a national level. This process will help ensure that decisions are financially sustainable. Any vaccine purchasing mechanisms should address the following essential points: 1) prioritization of cost-saving interventions; 2) flexible participation; 3) sufficient support to confront in-country challenges for managing vaccine procurement mechanisms; 4) a definite time-line for country ownership of vaccine purchases; 5) accuracy of vaccine demand forecasting; 6) maintenance of vaccine supply chains; and 7) well-functioning surveillance and regulatory bodies. In mapping the way forward, using the lessons learned and maintaining flexibility of financing and procurement mechanisms remain critical issues.
Fujkuyama, Yoshiko; Tokuhara, Daisuke; Kataoka, Kosuke; Gilbert, Rebekah S; McGhee, Jerry R; Yuki, Yoshikazu; Kiyono, Hiroshi; Fujihashi, Kohtaro
To develop protective immune responses against mucosal pathogens, the delivery route and adjuvants for vaccination are important. The host, however, strives to maintain mucosal homeostasis by responding to mucosal antigens with tolerance, instead of immune activation. Thus, induction of mucosal immunity through vaccination is a rather difficult task, and potent mucosal adjuvants, vectors or other special delivery systems are often used, especially in the elderly. By taking advantage of the common mucosal immune system, the targeting of mucosal dendritic cells and microfold epithelial cells may facilitate the induction of effective mucosal immunity. Thus, novel routes of immunization and antigen delivery systems also show great potential for the development of effective and safe mucosal vaccines against various pathogens. The purpose of this review is to introduce several recent approaches to induce mucosal immunity to vaccines, with an emphasis on mucosal tissue targeting, new immunization routes and delivery systems. Defining the mechanisms of mucosal vaccines is as important as their efficacy and safety, and in this article, examples of recent approaches, which will likely accelerate progress in mucosal vaccine development, are discussed. PMID:22380827
Crawley, Loretta; Frazer, Kate
This article debates whether posters as an assessment strategy in health professionals' education programmes can benefit learners, academics, and service users. Evidence suggests that service-user involvement benefits learning by developing students' communication, partnership and advocacy skills. The authors debate the value of posters as an assessment strategy in postgraduate diploma nursing programmes delivered in an Irish School of Nursing, Midwifery and Health Systems. It is argued that assessment strategies should not only examine programme theory and practice but should also benefit the people that will be using the service. Although the assessment strategy used in these programmes aimed to benefit service users, additional work is required for assessment to be truly inclusive of service users.
Raj K. Singh
Full Text Available Zika virus (ZIKV is the most recent intruder that acquired the status of global threat creating panic and frightening situation to public owing to its rapid spread, attaining higher virulence and causing complex clinical manifestations including microcephaly in newborns and Guillain Barré Syndrome. Alike other flaviviruses, the principal mode of ZIKV transmission is by mosquitoes. Advances in research have provided reliable diagnostics for detecting ZIKV infection, while several drug/therapeutic targets and vaccine candidates have been identified recently. Despite these progresses, currently there is neither any effective drug nor any vaccine available against ZIKV. Under such circumstances and to tackle the problem at large, control measures of which mosquito population control need to be strengthened following appropriate mechanical, chemical, biological and genetic control measures. Apart from this, several other known modes of ZIKV transmission which have gained importance in recent past such as intrauterine, sexual intercourse, and blood-borne spread need to be checked and kept under control by adopting appropriate precautions and utmost care during sexual intercourse, blood transfusion and organ transplantation. The virus inactivation by pasteurization, detergents, chemicals, and filtration can effectively reduce viral load in plasma-derived medicinal products. Added to this, strengthening of the surveillance and monitoring of ZIKV as well as avoiding travel to Zika infected areas would aid in keeping viral infection under check. Here, we discuss the salient advances in the prevention and control strategies to combat ZIKV with a focus on highlighting various intervention approaches against the vector mosquitoes of this viral pathogen along with presenting an overview regarding human intervention measures to counter other modes of ZIKV transmission and spread. Additionally, owing to the success of vaccines for a number of infections
Ellis, Jennifer M.; Reilly, Joan C.; Salazar, Juan C.
FluMist is the first live attenuated, cold-adapted intranasal influenza vaccine (LAIV) approved for the prevention of influenza A and B. Clinical trials have shown that annual vaccination with LAIV is effective for the prevention of influenza. LAIV appears well tolerated in healthy patients 5–49 years of age. The most common adverse events are abdominal pain, chills, cough, diarrhea, headache, irritability, lethargy, muscle aches, otitis media, rhinitis, sinusitis, sore throat, and vomiting. ...
Bijl, M.; Kallenberg, C.G.M.; van Assen, S.
Among immunocompromised patients morbidity and mortality due to vaccine-preventable infections is high. Although vaccination seems indicated, controversy exists about which vaccines should be offered, at what moment, and to whom. Guidelines are needed as the number of immunocompromised individuals
Behzad, Banafsheh; Jacobson, Sheldon H; Sewell, Edward C
This paper analyzes pricing strategies for US pediatric combination vaccines by comparing the lowest overall cost formularies (i.e., formularies that have the lowest overall cost). Three pharmaceutical companies compete pairwise over the sale of monovalent and combination vaccines. Particular emphasis is placed on examining the price of Sanofi Pasteur's DTaP-IPV/HIb under different conditions. The main contribution of the paper is to provide the lowest overall cost formularies for different prices of DTaP-IPV/HIb and other Sanofi Pasteur vaccines. The resulting analysis shows that DTaP-IPV/HIb could have been more competitively priced compared with the combination vaccine DTaP-HepB-IPV, for federal contract prices in 2009, 2010 and 2011. This study also proposes the lowest overall cost formularies when shortages of monovalent vaccines occur.
Daems, Rudi; Del Giudice, Giuseppe; Rappuoli, Rino
Flu pandemics (worldwide epidemics) have occurred at irregular and unpredictable intervals, and have been associated with substantial morbidity, mortality and economic cost. In response to the emerging potential for a new pandemic to occur, national and international preparedness plans are being drawn up specifying the use of antivirals and vaccines. A number of challenges to pandemic vaccine development, large-scale production and the timing of distribution have also been highlighted. This article reviews the rationale and consequential policy for aligned public- and private sector planning in the present inter-pandemic period despite the prevalent risks and uncertainties. We propose a model for product development of pandemic flu vaccine based on public-private partnership, including push and pull incentive mechanisms for stimulating work in this therapeutic area. In addition, we argue that innovative vaccination strategies, together with special vaccine formulations which may offer cross-protection against multiple flu pandemic strains might avert the worse effects of an influenza infection.
Full Text Available Two vaccines that protect against infection by some of the oncogenic human papillomavirus (HPV subtypes have recently been licensed for use in population-based vaccination strategies in many countries. However, these products are being promoted as ′cervical cancer vaccines′ based on inadequate data. Specifically, there remain several concerns about the duration of immunogenicity, length of follow-up of trial subjects, endpoints chosen in vaccine trials, applicability of trial results to real populations, the safety of these products, and their cost-effectiveness as public health interventions. Furthermore, it is unlikely that vaccination will obviate the need for setting up robust and cost-effective screening programs in countries like India. This article will discuss various aspects of HPV vaccination from a public health perspective, especially from the point of view of its relevance to India and other South Asian countries.
Kroneman, M.; Paget, J.
Background: Influenza continues to be a considerable health problem of the populations in Europe. Complications of influenza are especially present in elderly patients and patients with chronic conditions such as cardiovascular disorders and respiratory disorders. Vaccination is an effective
Rehn, Moa; Uhnoo, Ingrid; Kühlmann-Berenzon, Sharon; Wallensten, Anders; Sparén, Pär; Netterlid, Eva
The Swedish school-based vaccination programme offers HPV vaccine to girls born ≥1999 in 5-6th grade. In 2012, all counties introduced free-of-charge catch-up vaccination campaigns targeting girls born 1993-1998. Varying vaccine uptake in the catch-up group by December 2012 suggested that some implementation strategies were more successful than others. In order to inform future vaccination campaigns, we assessed the impact of different implementation strategies on the county-level catch-up vaccine uptake. We conducted an ecological study including all Swedish counties (n = 21), asking regional health offices about the information channels they used and where vaccination of the catch-up target group took place in their counties. The uptake of ≥1 dose by 30 September 2014 was estimated using data from the voluntary national vaccination register. We investigated associations between counties' catch-up vaccine uptake, information channels and vaccination settings by calculating incidence rate ratios (IRR) and 95% confidence intervals (CI), using negative binomial regression models. County level catch-up vaccine uptake varied between 49-84%. All counties offered vaccination through primary health care settings. Apart from this eight (34%) also offered the vaccine in some of their schools, four (19%) in all their schools, and two (10%) in other health care centres. The information channels most frequently used were: information at the national on-line health care consulting web-page (100%), letter/invitations (90%), and advertisement (81%). Counties offering vaccination to girls in all schools and counties offering vaccination in some of their schools, reached higher vaccine uptake compared to counties not offering vaccination in any of their schools (all schools adjusted IRR: 1.3, 95% CI: 1.1-1.5, some schools adjusted IRR: 1.2, 95% CI: 1.1-1.3). Counties offering HPV vaccination to catch-up groups in schools reached the highest vaccine uptake. No information
Full Text Available The Swedish school-based vaccination programme offers HPV vaccine to girls born ≥1999 in 5-6th grade. In 2012, all counties introduced free-of-charge catch-up vaccination campaigns targeting girls born 1993-1998. Varying vaccine uptake in the catch-up group by December 2012 suggested that some implementation strategies were more successful than others. In order to inform future vaccination campaigns, we assessed the impact of different implementation strategies on the county-level catch-up vaccine uptake.We conducted an ecological study including all Swedish counties (n = 21, asking regional health offices about the information channels they used and where vaccination of the catch-up target group took place in their counties. The uptake of ≥1 dose by 30 September 2014 was estimated using data from the voluntary national vaccination register. We investigated associations between counties' catch-up vaccine uptake, information channels and vaccination settings by calculating incidence rate ratios (IRR and 95% confidence intervals (CI, using negative binomial regression models.County level catch-up vaccine uptake varied between 49-84%. All counties offered vaccination through primary health care settings. Apart from this eight (34% also offered the vaccine in some of their schools, four (19% in all their schools, and two (10% in other health care centres. The information channels most frequently used were: information at the national on-line health care consulting web-page (100%, letter/invitations (90%, and advertisement (81%. Counties offering vaccination to girls in all schools and counties offering vaccination in some of their schools, reached higher vaccine uptake compared to counties not offering vaccination in any of their schools (all schools adjusted IRR: 1.3, 95% CI: 1.1-1.5, some schools adjusted IRR: 1.2, 95% CI: 1.1-1.3.Counties offering HPV vaccination to catch-up groups in schools reached the highest vaccine uptake. No information
Chin'ombe, Nyasha; Ruhanya, Vurayai
More than decades have already elapsed since human immunodeficiency virus (HIV) was identified as the causative agent of acquired immunodeficiency syndrome (AIDS). The HIV has since spread to all parts of the world with devastating effects. In sub-saharan Africa, the HIV/AIDS epidemic has reached unprecedented proportions. Safe, effective and affordable HIV/AIDS vaccines for Africans are therefore urgently needed to contain this public health problem. Although, there are challenges, there are also scientific opportunities and strategies that can be exploited in the development of HIV/AIDS vaccines for Africa. The recent RV144 Phase III trial in Thailand has demonstrated that it is possible to develop a vaccine that can potentially elicit modest protective immunity against HIV infection. The main objective of this review is to outline the key scientific opportunities, challenges and strategies in HIV/AIDS vaccine development in Africa.
Chin'ombe, Nyasha; Ruhanya, Vurayai
More than decades have already elapsed since human immunodeficiency virus (HIV) was identified as the causative agent of acquired immunodeficiency syndrome (AIDS). The HIV has since spread to all parts of the world with devastating effects. In sub-saharan Africa, the HIV/AIDS epidemic has reached unprecedented proportions. Safe, effective and affordable HIV/AIDS vaccines for Africans are therefore urgently needed to contain this public health problem. Although, there are challenges, there are also scientific opportunities and strategies that can be exploited in the development of HIV/AIDS vaccines for Africa. The recent RV144 Phase III trial in Thailand has demonstrated that it is possible to develop a vaccine that can potentially elicit modest protective immunity against HIV infection. The main objective of this review is to outline the key scientific opportunities, challenges and strategies in HIV/AIDS vaccine development in Africa. PMID:26185576
Full Text Available A new pneumococcal conjugate vaccine is currently undergoing advanced clinical evaluation prior to its planned introduction in Cuba. The implementation of the pneumococcal vaccination strategy has been designed with consideration of the need to maximize both its direct and indirect effects. A novel approach is suggested, which addresses preschool children as the first-line target group to generate herd immunity in infants and to have an impact on transmission at the community level. The clinical evaluation pipeline is described herein, including evaluations of effectiveness, cost-effectiveness, and impact. The scientific contribution of the Cuban strategy could support a paradigm shift from individual protection to a population effect based on a rigorous body of scientific evidence.
Wu, Yue; Wood, James; Khandaker, Gulam; Waddington, Claire; Snelling, Thomas
An estimated 110,000 babies are born with congenital rubella syndrome (CRS) worldwide annually; a significant proportion of cases occur in Southeast Asia. Rubella vaccine programs have led to successful control of rubella and CRS, and even the elimination of disease in many countries. However, if vaccination is poorly implemented it might increase the number of women reaching childbearing age who remain susceptible to rubella and thereby paradoxically increase CRS. We used an age-structured transmission model to compare seven alternative vaccine strategies for their impact on reducing CRS disease burden in East Java, a setting which is yet to implement a rubella vaccine program. We also investigated the robustness of model predictions to variation in vaccine coverage and other key epidemiological factors. Without rubella vaccination, approximately 700 babies are estimated to be born with CRS in East Java every year at an incidence of 0.77 per 1000live births. This incidence could be reduced to 0.0045 per 1000 live births associated with 99.9% annual reduction in rubella infections after 20 years if the existing two doses of measles vaccine are substituted with two doses of measles plus rubella combination vaccine with the same coverage (87.8% of 9-month-old infants and 80% of 6-year-old children). By comparison a single dose of rubella vaccine will take longer to reduce the burden of rubella and CRS and will be less robust to lower vaccine coverage. While the findings of this study should be informative for settings similar to East Java, the conclusions are dependent on vaccine coverage which would need consideration before applying to all of Indonesia and elsewhere in Asia. Copyright © 2016 Elsevier Ltd. All rights reserved.
Shepard, D. S.; Robertson, R. L.; Cameron, C. S.; Saturno, P.; Pollack, M.; Manceau, J.; Martínez, P.; Meissner, P.; Perrone, J.
A national household coverage survey of 3697 Ecuadorean children, carried out in July 1986, provided an opportunity for a cost-effectiveness analysis of (1) routine vaccination services based in fixed facilities and (2) mass immunization campaigns. A major purpose of the campaigns was to complement the routine services and to accelerate immunization activities. Based on the coverage survey, the Program for Reduction of Maternal and Childhood Illness (PREMI) and earlier campaigns increased the proportion of children under 5 years who were fully vaccinated from 43% to 64%. In one year, the PREMI campaign was responsible for fully vaccinating 11% of children under one year, 21% of 1-2-year-old children, and 13% of all children under 5 years. The campaign also helped ensure that vaccinations were completed when children were still very young and at greatest risk. The average cost per vaccination dose (in 1985 US$ prices) was approximately $0.29 for fixed facilities and $0.83 for the PREMI campaign. Total national costs were $675,000 and $1,665,000 for routine and campaign services respectively. The cost per fully vaccinated child (FVC) was $4.39 for routine vaccination services and $8.60 for the campaign. The cost per death averted was about $1900 for routine vaccination services, $4200 for the PREMI campaign, and $3200 for the combined programme. Because of Ecuador's lower mortality rates, the costs per death averted in Ecuador from both vaccination strategies are not as low as those from studies of vaccinations in Africa. The campaigns, though less cost-effective than routine services, significantly improved the vaccination coverage of younger children who had been missed by the routine services. The costs per FVC of both the campaign and the routine services compare favourably with such programmes in other countries. PMID:2517411
Surendran, Naveen; Sriranganathan, Nammalwar; Lawler, Heather; Boyle, Stephen M; Hiltbold, Elizabeth M; Heid, Bettina; Zimmerman, Kurt; Witonsky, Sharon G
Brucellosis is a zoonotic disease affecting 500,000 people worldwide annually. Inhalation of aerosol containing a pathogen is one of the major routes of disease transmission in humans. Currently there are no licensed human vaccines available. Brucella abortus strain RB51 is a USDA approved live attenuated vaccine against cattle brucellosis. In a mouse model, strain RB51 over-expressing superoxide dismutase (SOD) administered intraperitoneally (IP) has been shown to be more protective than strain RB51 against an IP challenge with B. abortus pathogenic strain 2308. However, there is lack of information on the ability of these vaccine strains to protect against intranasal challenge. With the long-term goal of developing a protective vaccine for animals and people against respiratory challenge of Brucella spp., we tested a number of different vaccination strategies against intranasal infection with strain 2308. We employed strains RB51 and RB51SOD to assess the efficacy of route, dose, and prime-boost strategies against strain 2308 challenge. Despite using multiple protocols to enhance mucosal and systemic protection, neither rough RB51 vaccine strains provided respiratory protection against intranasal pathogenic Brucella infection. However, intranasal (IN) administration of B. abortus vaccine strain 19 induced significant (p≤0.05) pulmonary clearance of strain 2308 upon IN challenge infection compared to saline. Further studies are necessary to address host-pathogen interaction in the lung microenvironment and elucidate immune mechanisms to enhance protection against aerosol infection. Published by Elsevier Ltd.
David A Garber
Full Text Available Modified Vaccinia virus Ankara (MVA is a safe, highly attenuated orthopoxvirus that is being developed as a recombinant vaccine vector for immunization against a number of infectious diseases and cancers. However, the expression by MVA vectors of large numbers of poxvirus antigens, which display immunodominance over vectored antigens-of-interest for the priming of T cell responses, and the induction of vector-neutralizing antibodies, which curtail the efficacy of subsequent booster immunizations, remain as significant impediments to the overall utility of such vaccines. Thus, genetic approaches that enable the derivation of MVA vectors that are antigenically less complex may allow for rational improvement of MVA-based vaccines.We have developed a genetic complementation system that enables the deletion of essential viral genes from the MVA genome, thereby allowing us to generate MVA vaccine vectors that are antigenically less complex. Using this system, we deleted the essential uracil-DNA-glycosylase (udg gene from MVA and propagated this otherwise replication-defective variant on a complementing cell line that constitutively expresses the poxvirus udg gene and that was derived from a newly identified continuous cell line that is permissive for growth of wild type MVA. The resulting virus, MVADeltaudg, does not replicate its DNA genome or express late viral gene products during infection of non-complementing cells in culture. As proof-of-concept for immunological 'focusing', we demonstrate that immunization of mice with MVADeltaudg elicits CD8+ T cell responses that are directed against a restricted repertoire of vector antigens, as compared to immunization with parental MVA. Immunization of rhesus macaques with MVADeltaudg-gag, a udg(- recombinant virus that expresses an HIV subtype-B consensus gag transgene, elicited significantly higher frequencies of Gag-specific CD8 and CD4 T cells following both primary (2-4-fold and booster (2-fold
Mena, Guillermo; Llupià, Anna; García-Basteiro, Alberto L; Sequera, Victor-Guillermo; Aldea, Marta; Bayas, José María; Trilla, Antoni
Influenza vaccination coverage in medical students is usually low. Unlike health care workers, there is little information on the attitudes to and predictors of vaccination among medical students, and their attitudes towards institutional strategies for improving rates are unknown. This cross-sectional study evaluated the effect of three influenza vaccination promotional strategies (Web page, video and tri-fold brochure) on medical students' intention to get vaccinated and associated factors. A total of 538 medical students were asked to answer an anonymous questionnaire assessing the intention to get vaccinated after exposure to any of the promotional strategies. Sociodemographic data collected included: sex, age, university year, influenza risk group and cohabiting with member of a risk group. Four hundred twenty-one students answered the questionnaire, of whom 312 (74.1%) were female, 113 (26.8%) had done clinical rotations, and 111 (26.6%) reported intention to get the flu shot. Logistic regression showed the web group had a greater intention to get vaccinated than the reference group (OR: 2.42 95% CI: 1.16-5.03). Having done clinical rotations (OR: 2.55 95% CI: 1.36-4.38) and having received the shot in previous flu seasons (OR: 13.69 95% CI: 7.86-23.96) were independently associated with the intention to get vaccinated. Given that previous vaccination is a factor associated with the intention to get vaccinated, education on vaccination of health care workers should begin while they are students, thereby potentiating the habit. In addition, the intention to get vaccinated was greater during the clinical phase of the university career, suggesting this is a good time to introduce promotion strategies. Online promotional campaigns, such as a thematic Web to promote vaccination of health workers, could improve the intention to get vaccinated.
Sala, Francesco; Manuela Rigano, M; Barbante, Alessandra; Basso, Barbara; Walmsley, Amanda M; Castiglione, Stefano
Stable integration of a gene into the plant nuclear or chloroplast genome can transform higher plants (e.g. tobacco, potato, tomato, banana) into bioreactors for the production of subunit vaccines for oral or parental administration. This can also be achieved by using recombinant plant viruses as transient expression vectors in infected plants. The use of plant-derived vaccines may overcome some of the major problems encountered with traditional vaccination against infectious diseases, autoimmune diseases and tumours. They also offer a convenient tool against the threat of bio-terrorism. State of the art, experimental strategies, safety and perspectives are discussed in this article.
The objective of this study was to determine if Learning-Focused Strategies (LFS) implemented in high school science courses would affect student achievement and the pass rate of biology and physical science Common District Assessments (CDAs). The LFS, specific teaching strategies contained in the Learning-Focused Strategies Model (LFSM) Program…
Epitope mapping of Ebola virus dominant and subdominant glycoprotein epitopes facilitates construction of an epitope-based DNA vaccine able to focus... vaccinated against or infected with EBOV. Using the information obtained along with structural modeling to predict epitope accessibility, we then...constructed two DNA vaccines encoding immunodominant and subdominant epitopes predicted to be accessible on EBOV GP. Although a construct designed to
J. Kesecioglu (Jozef)
textabstractThis thesis focuses on comparison of different modes of ventilation in animals and patients with ARDS. The aim is to determine the immediate advantages of one mode over the other in terms of gas exchange, airway pressures,' hemodynamics and ventilation inhomogeneity.
Locher, Christopher P; Soong, Nay Wei; Whalen, Robert G; Punnonen, Juha
DNA shuffling and screening technologies recombine and evolve genes in vitro to rapidly obtain molecules with improved biological activity and fitness. In this way, genes from related strains are bred like plants or livestock and their successive progeny are selected. These technologies have also been called molecular breeding-directed molecular evolution. Recent developments in bioinformatics-assisted computer programs have facilitated the design, synthesis and analysis of DNA shuffled libraries of chimeric molecules. New applications in vaccine development are among the key features of DNA shuffling and screening technologies because genes from several strains or antigenic variants of pathogens can be recombined to create novel molecules capable of inducing immune responses that protect against infections by multiple strains of pathogens. In addition, molecules such as co-stimulatory molecules and cytokines have been evolved to have improved T-cell proliferation and cytokine production compared with the wild-type human molecules. These molecules can be used to immunomodulate vaccine responsiveness and have multiple applications in infectious diseases, cancer, allergy and autoimmunity. Moreover, DNA shuffling and screening technologies can facilitate process development of vaccine manufacturing through increased expression of recombinant polypeptides and viruses. Therefore, DNA shuffling and screening technologies can overcome some of the challenges that vaccine development currently faces.
Chen, Z M; Ji, S B; Shi, X L; Zhao, Y Y; Zhang, X F; Jin, H
Objective: To evaluate the cost-utility of different hepatitis E vaccination strategies in women aged 15 to 49. Methods: The Markov-decision tree model was constructed to evaluate the cost-utility of three hepatitis E virus vaccination strategies. Parameters of the models were estimated on the basis of published studies and experience of experts. Both methods on sensitivity and threshold analysis were used to evaluate the uncertainties of the model. Results: Compared with non-vaccination group, strategy on post-screening vaccination with rate as 100%, could save 0.10 quality-adjusted life years per capital in the women from the societal perspectives. After implementation of screening program and with the vaccination rate reaching 100%, the incremental cost utility ratio (ICUR) of vaccination appeared as 5 651.89 and 6 385.33 Yuan/QALY, respectively. Vaccination post to the implementation of a screening program, the result showed better benefit than the vaccination rate of 100%. Results from the sensitivity analysis showed that both the cost of hepatitis E vaccine and the inoculation compliance rate presented significant effects. If the cost were lower than 191.56 Yuan (RMB) or the inoculation compliance rate lower than 0.23, the vaccination rate of 100% strategy was better than the post-screening vaccination strategy, otherwise the post-screening vaccination strategy appeared the optimal strategy. Conclusion: Post-screening vaccination for women aged 15 to 49 from social perspectives seemed the optimal one but it had to depend on the change of vaccine cost and the rate of inoculation compliance.
Tain, You-Lin; Joles, Jaap A.
Adulthood hypertension can be programmed in response to a suboptimal environment in early life. However, developmental plasticity also implies that one can prevent hypertension in adult life by administrating appropriate compounds during early development. We have termed this reprogramming. While the risk of hypertension has been assessed in many mother-child cohorts of human developmental programming, interventions necessary to prove causation and provide a reprogramming strategy are lacking. Since the developing kidney is particularly vulnerable to environmental insults and blood pressure is determined by kidney function, renal programming is considered key in developmental programming of hypertension. Common pathways, whereby both genetic and acquired developmental programming converge into the same phenotype, have been recognized. For instance, the same reprogramming interventions aimed at shifting nitric oxide (NO)-reactive oxygen species (ROS) balance, such as perinatal citrulline or melatonin supplements, can be protective in both genetic and developmentally programmed hypertension. Furthermore, a significantly increased expression of gene Ephx2 (soluble epoxide hydrolase) was noted in both genetic and acquired animal models of hypertension. Since a suboptimal environment is often multifactorial, such common reprogramming pathways are a practical finding for translation to the clinic. This review provides an overview of potential clinical applications of reprogramming strategies to prevent programmed hypertension. We emphasize the kidney in the following areas: mechanistic insights from human studies and animal models to interpret programmed hypertension; identified risk factors of human programmed hypertension from mother-child cohorts; and the impact of reprogramming strategies on programmed hypertension from animal models. It is critical that the observed effects on developmental reprogramming in animal models are replicated in human studies. PMID
Full Text Available 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
Botwright, Siobhan; Holroyd, Taylor; Nanda, Shreya; Bloem, Paul; Griffiths, Ulla K; Sidibe, Anissa; Hutubessy, Raymond C W
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
Walker, Robrina; Stephens, Robert S
Protective behavioral strategies have emerged as a construct protective against alcohol use. The current study examines the theoretical associations among general coping styles, protective behavioral strategies, drinking to cope motives, and alcohol use in college students. Analyses of fully latent variables were conducted using structural equation modeling in a sample of 327 college students. Protective behavioral strategies partially mediated the association between problem-focused coping and alcohol use. Behaviorally oriented problem-focused coping strategies accounted for the positive relationship between problem-focused coping and protective behavioral strategies whereas cognitively oriented problem-focused coping strategies were associated with less use of protective behavioral strategies and increased alcohol use. This is the first study to find that protective behavioral strategies are more likely to be used by college students who endorse using a problem-focused coping style, especially if they tend to use behaviorally oriented problem-focused coping strategies. These findings extend the literature on protective behavioral strategies and indicate that students less likely to use problem-focused coping skills to deal with stress in general may need additional interventions to increase their use of protective behavioral strategies. Copyright © 2014 Elsevier Ltd. All rights reserved.
Full Text Available Cervical cancer is one of the most common cancers in women worldwide, particularly in developing countries. The viral origin of cervical cancer has been proven beyond any reasonable doubt. Persistent infection with certain subsets of human papillomaviruses is recognized as a necessary cause for the development of cervical cancer. Persistence of oncogenic HPVs, immunodeficiency, high HPV viral load and cofactors like smoking, multiple sex partners and poor nutrition predispose to cervical cancer. Prophylactic vaccines using HPV virus-like particles containing capsid protein L1 have shown protection against disease in animals and are currently undergoing clinical trials. Therapeutic vaccines using HPV E6 and E7 proteins are also being investigated for their ability to remove residual infection.
Hughes, Claude; Waters, Michael; Allen, David; Obasanjo, Iyabo
Given that toxicology studies the potential adverse effects of environmental exposures on various forms of life and that clinical toxicology typically focuses on human health effects, what can and should the relatively new term of "translational toxicology" be taken to mean? Our assertion is that the core concept of translational toxicology must incorporate existing principles of toxicology and epidemiology, but be driven by the aim of developing safe and effective interventions beyond simple reduction or avoidance of exposure to prevent, mitigate or reverse adverse human health effects of exposures.The field of toxicology has now reached a point where advances in multiple areas of biomedical research and information technologies empower us to make fundamental transitions in directly impacting human health. Translational toxicology must encompass four action elements as follows: 1) Assessing human exposures in critical windows across the lifespan; 2) Defining modes of action and relevance of data from animal models; 3) Use of mathematical models to develop plausible predictions as the basis for: 4) Protective and restorative human health interventions. The discussion focuses on the critical window of in-utero development. Exposure assessment, basic toxicology and development of certain categories of mathematical models are not new areas of research; however overtly integrating these in order to conceive, assess and validate effective interventions to mitigate or reverse adverse effects of environmental exposures is our novel opportunity. This is what we should do in translational toxicology so that we have a portfolio of interventional options to improve human health that include both minimizing exposures and specific preventative/restorative/mitigative therapeutics.
Yu, Mingke; Vajdy, Michael
There are currently over thirty million people infected with HIV and there are no vaccines available to prevent HIV infections or disease. The genitourinary, rectal and oral mucosa are the mucosal HIV transmission routes. An effective vaccine that can induce both systemic and local mucosal immunity is generally accepted as a major means of protection against mucosal HIV transmission and AIDS. Structure and cells that comprise the oral, vaginal and rectal mucosa pertaining to HIV transmission and vaccination strategies through each mucosal route to prevent mucosal and systemic infection will be discussed. Covering publications from 1980s through 2010, mucosal transmission of HIV and current and previous approaches to vaccinations are discussed. Although oral transmission of HIV is far less common than vaginal and rectal transmissions, infections through this route do occur through oral sex as well as vertically from mother to child. Mucosal vaccination strategies against oral and other mucosal HIV transmissions are under intensive research but the lack of consensus on immune correlates of protection and lack of safe and effective mucosal adjuvants and delivery systems hamper progress towards a licensed vaccine.
Friesen, Johannes; Matuschewski, Kai
Despite major efforts over the past 50 years to develop a malaria vaccine, no product has been licensed yet. Irradiated sporozoites are the benchmark for an experimental live-attenuated malaria vaccine that induces potent protection against re-infection in humans and animal models. Lasting protection can also be elicited by parasite attenuation via tailored genetic modification or drug cover leading to renewed interest in whole-organism vaccination strategies. In this study, we systematically compared the protective efficacy of different whole-organism vaccination approaches in the Plasmodium berghei/C57bl/6 rodent malaria model. We applied blood stage parasitemia and quantitative RT-PCR of liver parasite loads as two complementary primary endpoints of a malaria challenge infection. We were able to demonstrate similar potency of genetic attenuation, i.e., uis3(-) and p36p(-) parasites, and prophylactic drug cover, i.e., azithromycin, pyrimethamine, primaquine and chloroquine, during sporozoite exposure in comparison to irradiated sporozoites. Importantly, when animals were covered with the antibiotic azithromycin during sporozoite exposure we observed superior protection. On the other end, immunizations with heat-killed and over-irradiated sporozoites failed to confer any detectable protection. Together, we show that systematic pre-clinical evaluation and quantification of vaccine efficacy is vital for identification of the most potent whole organism anti-malaria vaccine strategy. Copyright © 2011 Elsevier Ltd. All rights reserved.
Weck, M; Bornstein, S R; Barthel, A; Blüher, M
The prevalence of obesity and related health problems is increasing worldwide and also in Germany. It is well known that substantial and sustained weight loss is difficult to accomplish. Therefore, a variety of studies has been performed in order to specify causes for weight gain and create hypotheses for better treatment options. Key factors of this problem are an adaptation of energy metabolism, especially resting metabolic rate (RMR), non-exercise thermogenesis and diet induced thermogenesis. The extremely high failure rate (> 80%) to keep the reduced weight after successful weight loss is due to adaptation processes of the body to maintain body energy stores. This so called "adaptive thermogenesis" is defined as a smaller than predicted change of energy expenditure in response to changes in energy balance. Adaptive thermogenesis appears to be a major reason for weight regain. The foremost objective of weight-loss programs is the reduction in body fat. However, a concomitant decline in lean tissue can frequently be observed. Since lean body mass (LBM) represents a key determinant of RMR it follows that a decrease in lean tissue could counteract the progress of weight loss. Therefore, with respect to long-term effectiveness of weight reduction programs, the loss of fat mass while maintaining LBM and RMR seems desirable. In this paper we will discuss the mechanisms of adaptive thermogenesis and develop therapeutic strategies with respect to avoiding weight regain successful weight reduction. © Georg Thieme Verlag KG Stuttgart · New York.
Coughlin, Melissa M; Beck, Andrew S; Bankamp, Bettina; Rota, Paul A
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.
Oku, Afiong; Oyo-Ita, Angela; Glenton, Claire; Fretheim, Atle; Ames, Heather; Muloliwa, Artur; Kaufman, Jessica; Hill, Sophie; Cliff, Julie; Cartier, Yuri; Bosch-Capblanch, Xavier; Rada, Gabriel; Lewin, Simon
Effective communication is a critical component in ensuring that children are fully vaccinated. Although numerous communication interventions have been proposed and implemented in various parts of Nigeria, the range of communication strategies used has not yet been mapped systematically. This study forms part of the 'Communicate to vaccinate' (COMMVAC) project, an initiative aimed at building research evidence for improving communication with parents and communities about childhood vaccinations in low- and middle-income countries. This study aims to: 1) identify the communication strategies used in two states in Nigeria; 2) map these strategies against the existing COMMVAC taxonomy, a global taxonomy of vaccination communication interventions; 3) create a specific Nigerian country map of interventions organised by purpose and target; and 4) analyse gaps between the COMMVAC taxonomy and the Nigerian map. We conducted the study in two Nigerian states: Bauchi State in Northern Nigeria and Cross River State in Southern Nigeria. We identified vaccination communication interventions through interviews carried out among purposively selected stakeholders in the health services and relevant agencies involved in vaccination information delivery; through observations and through relevant documents. We used the COMMVAC taxonomy to organise the interventions we identified based on the intended purpose of the communication and the group to which the intervention was targeted. The Nigerian map revealed that most of the communication strategies identified aimed to inform and educate and remind or recall. Few aimed to teach skills, enhance community ownership, and enable communication. We did not identify any intervention that aimed to provide support or facilitate decision-making. Many interventions had more than one purpose. The main targets for most interventions were caregivers and community members, with few interventions directed at health workers. Most interventions
Full Text Available Nonalcoholic fatty liver disease (NAFLD is the most common chronic liver disease in the Western world (it affects 30% of the general adult population. The NAFLD encompasses a histological spectrum ranging from simple steatosis to nonalcoholic steatohepatitis (NASH, defined by steatosis, hepatocellular damage, and lobular inflammation in individuals without significant alcohol consumption and negative viral, congenital, and autoimmune liver disease markers. Currently, NAFLD is considered an emerging epidemic in light of the dramatic increase in obesity rates. With the progressive nature of NASH and its rising prevalence there is a significant need for a specific and targeted treatments since to date there has not been any validated therapies for NAFLD other than weight loss, which is well known to have a poor long-term success rate. In recent years, visceral adipose tissue has taken an important role in NAFLD pathogenesis, and current therapeutic approaches aim at reducing visceral obesity and free fatty acid overflow to the liver. This paper is focused on the treatments used for NAFLD and the potential new therapy.
van Kleef, Esther; Deeny, Sarah R; Jit, Mark; Cookson, Barry; Goldenberg, Simon D; Edmunds, W John; Robotham, Julie V
Early clinical trials of a Clostridium difficile toxoid vaccine show efficacy in preventing C. difficile infection (CDI). The optimal patient group to target for vaccination programmes remains unexplored. This study performed a model-based evaluation of the effectiveness of different CDI vaccination strategies, within the context of existing infection prevention and control strategies such as antimicrobial stewardship. An individual-based transmission model of CDI in a high-risk hospital setting was developed. The model incorporated data on patient movements between the hospital, and catchment populations from the community and long-term care facilities (LTCF), using English national and local level data for model-parameterisation. We evaluated vaccination of: (1) discharged patients who had an CDI-occurrence in the ward; (2) LTCF-residents; (3) Planned elective surgical admissions and (4) All three strategies combined. Without vaccination, 10.9 [Interquartile range: 10.0-11.8] patients per 1000 ward admissions developed CDI, of which 31% were ward-acquired. Immunising all three patient groups resulted in a 43% [42-44], reduction of ward-onset CDI on average. Among the strategies restricting vaccination to one target group, vaccinating elective surgical patients proved most effective (35% [34-36] reduction), but least efficient, requiring 146 [133-162] courses to prevent one ICU-onset case. Immunising LTCF residents was most efficient, requiring just 13 [11-16] courses to prevent one case, but considering this only comprised a small group of our hospital population, it only reduced ICU-onset CDI by 9% [8-11]. Vaccination proved most efficient when ward-based transmission rates and antimicrobial consumption were high. Strategy success depends on the interaction between hospital and catchment populations, and importantly, consideration of importations of CDI from outside the hospital which we found to substantially impact hospital dynamics. Vaccination may be most
Smith, Michael J; Woods, Charles R; Marshall, Gary S
An increasing number of parents are questioning the safety and necessity of routine childhood immunizations. Locally produced vaccine risk communication materials may be effective in reassuring these parents. However, little is known about specific vaccine safety concerns in the state of Kentucky. An Internet-based survey focusing on parental vaccine safety concerns and potential vaccine risk communication strategies was sent to all members of the Kentucky Chapter of the Amerian Academy of Pediatrics. There were 121 respondents who routinely administered childhood vaccines. Of these, 85% reported parental concern about the combined measles-mumps-rubella (MMR) vaccine. Concerns about the influenza and human papillomavirus (HPV) vaccines were also frequent. Of the respondents, 46% noted parental skepticism about all vaccines in general. However, refusal of all vaccines was uncommon in most practices (median 1%, interquartile range 1%-3%). The belief that vaccines cause autism was the most prevalent parental concern, reported by 70% of pediatricians. Physicians also reported that a list of reliable vaccine information Websites and pamphlets addressing common vaccine safety concerns would be the most helpful materials to use during their discussions with concerned parents. These findings suggest that specific information about the MMR, influenza, and HPV vaccines, as well as data refuting the putative link between vaccines and autism would be useful to physicians who administer vaccinations. Respondents were especially interested in reliable vaccine information on the Internet. The Websites listed below offer accurate scientific information about vaccines and the diseases they prevent.
Jang, Eun-Young; Jimenez, Robert T.
Studies on second language (L2) learners' strategies tended to characterize strategies as individual learners' cognitive predispositions or personality traits, leaving a critical question unanswered: Why do learners use different strategies in different contexts? From a sociocultural perspective, this article pursued this question by focusing on…
Oku, Afiong; Oyo-Ita, Angela; Glenton, Claire; Fretheim, Atle; Ames, Heather; Muloliwa, Artur; Kaufman, Jessica; Hill, Sophie; Cliff, Julie; Cartier, Yuri; Bosch-Capblanch, Xavier; Rada, Gabriel; Lewin, Simon
Background Effective communication is a critical component in ensuring that children are fully vaccinated. Although numerous communication interventions have been proposed and implemented in various parts of Nigeria, the range of communication strategies used has not yet been mapped systematically. This study forms part of the ‘Communicate to vaccinate’ (COMMVAC) project, an initiative aimed at building research evidence for improving communication with parents and communities about childhood vaccinations in low- and middle-income countries. Objective This study aims to: 1) identify the communication strategies used in two states in Nigeria; 2) map these strategies against the existing COMMVAC taxonomy, a global taxonomy of vaccination communication interventions; 3) create a specific Nigerian country map of interventions organised by purpose and target; and 4) analyse gaps between the COMMVAC taxonomy and the Nigerian map. Design We conducted the study in two Nigerian states: Bauchi State in Northern Nigeria and Cross River State in Southern Nigeria. We identified vaccination communication interventions through interviews carried out among purposively selected stakeholders in the health services and relevant agencies involved in vaccination information delivery; through observations and through relevant documents. We used the COMMVAC taxonomy to organise the interventions we identified based on the intended purpose of the communication and the group to which the intervention was targeted. Results The Nigerian map revealed that most of the communication strategies identified aimed to inform and educate and remind or recall. Few aimed to teach skills, enhance community ownership, and enable communication. We did not identify any intervention that aimed to provide support or facilitate decision-making. Many interventions had more than one purpose. The main targets for most interventions were caregivers and community members, with few interventions directed at
Rozenbaum, M.H.; De Vries, R.; Le, H.H.; Postma, M.J.
The aim of this study was to investigate the optimal pertussis booster vaccination strategy for The Netherlands. A realistic age-structured deterministic model was designed. Assuming a steady-state situation and correcting for underreporting, the model was calibrated using notification data from the
Ferreira, Marcos Roberto A.; Moreira, Gustavo Marçal S. G.; da Cunha, Carlos Eduardo P.; Mendonça, Marcelo; Salvarani, Felipe M.; Moreira, Ângela N.; Conceição, Fabricio R.
Clostridium perfringens is a spore-forming, commensal, ubiquitous bacterium that is present in the gastrointestinal tract of healthy humans and animals. This bacterium produces up to 18 toxins. The species is classified into five toxinotypes (A–E) according to the toxins that the bacterium produces: alpha, beta, epsilon, or iota. Each of these toxinotypes is associated with myriad different, frequently fatal, illnesses that affect a range of farm animals and humans. Alpha, beta, and epsilon toxins are the main causes of disease. Vaccinations that generate neutralizing antibodies are the most common prophylactic measures that are currently in use. These vaccines consist of toxoids that are obtained from C. perfringens cultures. Recombinant vaccines offer several advantages over conventional toxoids, especially in terms of the production process. As such, they are steadily gaining ground as a promising vaccination solution. This review discusses the main strategies that are currently used to produce recombinant vaccines containing alpha, beta, and epsilon toxins of C. perfringens, as well as the potential application of these molecules as vaccines for mammalian livestock animals. PMID:27879630
Desiante, F; Russo, C; Giorgino, A; Caputi, G; Battista, T; Cipriani, R; Conversano, M
A promising approach to increase teenager's adherence to immunization against HPV is the administration of vaccinations within the school facilities. The Local Health Unit of Taranto experienced two different vaccine strategy proposals in the twelve-year-olds: the first one was the usual active call strategy in the outpatient clinic, while the second one provided the involvement of the schools in the area. The aim of the study is to evaluate the results of the proposed vaccination strategies in both sexes and in towns of different sizes in order to identify an effective path for achieving vaccine coverage improvement. To estimate the number of anti-HPV vaccine doses administered in adolescents of the 2003 cohort, we used the computerized vaccination system data of the Apulia Region. Then, once analyzed, the data for anti-HPV vaccine were broken down by gender, vaccine strategy and size of the town of residence. Analyses performed by using STATA SE 14. The multiple logistic regression points out that, females (OR = 3.2; p HPV vaccine cycle in adolescents. The comparative assessment of anti-HPV coverage strategies, suggests that school vaccination has resulted in significantly better outcomes than outpatient clinic one, for all the groups considered (overall 72.3% vs 55.6%). The involvement of school institutes can define a winning organizational model to get a wider adolescent's adherence to immunization programs, especially in bigger towns. The school vaccination strategy could improve anti-HPV vaccine adherence also in males, who perceives a lower HPV-related diseases risk than females.
Lungarde, Karine; Blaizeau, Fanette; Auger-Aubin, Isabelle; Floret, Daniel; Gilberg, Serge; Jestin, Christine; Hanslik, Thomas; Le Goaster, Corinne; Lévy-Bruhl, Daniel; Blanchon, Thierry; Rossignol, Louise
As in other European countries, the French vaccination schedule changes according to epidemiological and socio-economic situations. Further changes are planned for 2013, including the withdrawal of one dose for primary vaccination against diphtheria, tetanus, polio, pertussis and Haemophilus influenzae. A partnership between the French Technical Vaccination Committee and the French Institute for Health and Medical Research designed a study to assess primary care physicians' agreement about this modification. Qualitative study with focus groups and semi-structured interviews in France. Four focus groups were conducted with physicians, supplemented by four individual interviews. The physicians of the survey had accepted the suggested vaccination schedule well. A few concerns had been underlined: fear of less follow-up care for infants resulting from the removal of one visit driven by the primary vaccination; fear of loss of vaccine efficacy; suspicion of the existence of financial arguments at the origin of this change; and adjustment to current vaccination schedule. Several suggestions were made: providing strong support from health authorities; developing stable and simple recommendations; providing effective tools for monitoring patient's vaccination status. Physicians' opinions suggested a good acceptance of a possible change about primary vaccination against diphtheria, tetanus, polio, pertussis and Haemophilus influenzae. Physicians' suggestions resulted from this qualitative study on a new vaccination schedule. It showed how that their involvement was feasible for preparing the implementation of a new vaccination schedule.
Full Text Available Neonates have an immature immune system which cannot adequately protect against infectious diseases. Early in life, immune protection is accomplished by maternal antibodies transferred from mother to offspring. However, decaying maternal antibodies inhibit vaccination as is examplified by the inhibition of seroconversion after measles vaccination. This phenomenon has been described in both human and veterinary medicine and is independent of the type of vaccine being used. This review will discuss the use of animal models for vaccine research. I will review clinical solutions for inhibition of vaccination by maternal antibodies, and the testing and development of potentially effective vaccines. These are based on new mechanistic insight about the inhibitory mechanism of maternal antibodies. Maternal antibodies inhibit the generation of antibodies whereas the T cell response is usually unaffected. B cell inhibition is mediated through a cross-link between B-cell receptor (BCR with the Fcg receptor IIB (FcgRIIB by a vaccine-antibody complex. In animal experiments, this inhibition can be partially overcome by injection of a vaccine-specific monoclonal IgM antibody. IgM stimulates the B-cell directly through cross-linking the BCR via complement protein C3d and antigen to the complement receptor 2 (CR2 signaling complex. In addition, it was shown that interferon alpha binds to the CD21 chain of CR2 as well as the interferon receptor and that this dual receptor usage drives B cell responses in the presence of maternal antibodies. In lieu of immunizing the infant the concept of maternal immunization as a strategy to protect neonates has been proposed. This approach would still not solve the question of how to immunize in the presence of maternal antibodies but would defer the time of infection to an age where infection might not have such a detrimental outcome as in neonates. I will review successful examples and potential challenges of implementing
Signe Tandrup Schmidt
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
van Donk, D.P.; van der Vaart, T.
Purpose - The concept of buyer focus has recently been introduced as a new supply chain strategy, although the design and operation of buyer-focused cells have hardly been investigated. The purpose of this paper is to investigate how buyer-focused cells realise responsiveness.
MacLennan, Calman A.; Saul, Allan
With the 2010s declared the Decade of Vaccines, and Millennium Development Goals 4 and 5 focused on reducing diseases that are potentially vaccine preventable, now is an exciting time for vaccines against poverty, that is, vaccines against diseases that disproportionately affect low- and middle-income countries (LMICs). The Global Burden of Disease Study 2010 has helped better understand which vaccines are most needed. In 2012, US$1.3 billion was spent on research and development for new vaccines for neglected infectious diseases. However, the majority of this went to three diseases: HIV/AIDS, malaria, and tuberculosis, and not neglected diseases. Much of it went to basic research rather than development, with an ongoing decline in funding for product development partnerships. Further investment in vaccines against diarrheal diseases, hepatitis C, and group A Streptococcus could lead to a major health impact in LMICs, along with vaccines to prevent sepsis, particularly among mothers and neonates. The Advanced Market Commitment strategy of the Global Alliance for Vaccines and Immunisation (GAVI) Alliance is helping to implement vaccines against rotavirus and pneumococcus in LMICs, and the roll out of the MenAfriVac meningococcal A vaccine in the African Meningitis Belt represents a paradigm shift in vaccines against poverty: the development of a vaccine primarily targeted at LMICs. Global health vaccine institutes and increasing capacity of vaccine manufacturers in emerging economies are helping drive forward new vaccines for LMICs. Above all, partnership is needed between those developing and manufacturing LMIC vaccines and the scientists, health care professionals, and policy makers in LMICs where such vaccines will be implemented. PMID:25136089
MacLennan, Calman A; Saul, Allan
With the 2010s declared the Decade of Vaccines, and Millennium Development Goals 4 and 5 focused on reducing diseases that are potentially vaccine preventable, now is an exciting time for vaccines against poverty, that is, vaccines against diseases that disproportionately affect low- and middle-income countries (LMICs). The Global Burden of Disease Study 2010 has helped better understand which vaccines are most needed. In 2012, US$1.3 billion was spent on research and development for new vaccines for neglected infectious diseases. However, the majority of this went to three diseases: HIV/AIDS, malaria, and tuberculosis, and not neglected diseases. Much of it went to basic research rather than development, with an ongoing decline in funding for product development partnerships. Further investment in vaccines against diarrheal diseases, hepatitis C, and group A Streptococcus could lead to a major health impact in LMICs, along with vaccines to prevent sepsis, particularly among mothers and neonates. The Advanced Market Commitment strategy of the Global Alliance for Vaccines and Immunisation (GAVI) Alliance is helping to implement vaccines against rotavirus and pneumococcus in LMICs, and the roll out of the MenAfriVac meningococcal A vaccine in the African Meningitis Belt represents a paradigm shift in vaccines against poverty: the development of a vaccine primarily targeted at LMICs. Global health vaccine institutes and increasing capacity of vaccine manufacturers in emerging economies are helping drive forward new vaccines for LMICs. Above all, partnership is needed between those developing and manufacturing LMIC vaccines and the scientists, health care professionals, and policy makers in LMICs where such vaccines will be implemented.
Boccalini, Sara; Bechini, Angela; Gasparini, Roberto; Panatto, Donatella; Amicizia, Daniela; Bonanni, Paolo
Many evaluations have been performed on the economic impact of pneumococcal vaccination in older adults (>64 y of age) in several countries, including Italy. However, these studies did not include the new data on the effectiveness of 13-valent conjugate pneumococcal vaccine (PCV13) in the elderly reported by the CAPiTA Study. The aim of the present study was to update our previous budget impact analysis of multi-cohort PCV13 vaccination in adults in Italy by including new scientific evidence. We also compared single-cohort vaccination strategies per year, in order to identify the cohort with the most favorable economic profile, in the event of the multi-cohort approach not being economically sustainable for the National Health System (NHS). The new impact analysis highlights that the vaccination of one, two or three adult cohorts per year in Italy would lead to a considerable reduction in pneumococcal disease and its related costs over 5 y. The strategies proved cost-effective (ICERs ranging from €14,605 to €15,412/QALY), i.e. well below the threshold of €50,000/QALY. The ICERs were slightly lower than those calculated in the first published analysis and vaccination continued to be economically favorable. In the case of a mono-cohort strategy, the vaccination of 65-year-old subjects, albeit more expensive, proved to be more favorable than the vaccination of 70- or 75-year-old cohorts. Finally, after the inclusion of the recent clinical evidence, the age-based PCV13 vaccination of the elderly in Italy continued to be economically justified from the NHS perspective in the short period. Vaccination of the elderly should therefore be strongly recommended nationwide in Italy.
Rejane L. Petersen
Full Text Available Bio-layer interferometry (BLI real-time, label-free technology has greatly contributed to advances in vaccine research and development. BLI Octet platforms offer high-throughput, ease of use, reliability, and high precision analysis when compared with common labeling techniques. Many different strategies have been used to immobilize the pathogen or host molecules on BLI biosensors for real-time kinetics and affinity analysis, quantification, or high-throughput titer. These strategies can be used in multiple applications and shed light onto the structural and functional aspects molecules play during pathogen-host interactions. They also provide crucial information on how to achieve protection. This review summarizes some key BLI strategies used in human vaccine research and development.
Bechini, Angela; Bonanni, Paolo; Lauri, Sara; Tiscione, Emilia; Levi, Miriam; Prato, Rosa; Fortunato, Francesca; Martinelli, Domenico; Gasparini, Roberto; Panatto, Donatella; Amicizia, Daniela; Coppola, Rosa Cristina; Pellizzari, Barbara; Tabacchi, Garden; Costantino, Claudio; Vitale, Francesco; Iannazzo, Stefania; Boccalini, Sara
The ESCULAPIO Project aims at increasing awareness on vaccine preventable infectious diseases (VPID) and vaccinations in different target populations and to spread the culture of prevention. Information/training interventions on VPID have been developed and health promotion activities for the general population, students and their parents, teachers and health care workers (HCWs) were set up. In Tuscany, educational courses on VPID in high schools were organized and students were stimulated to prepare informative materials on VPID for lower grade school pupils. In Liguria, an educational card game (named 'Vaccine at the Fair') was presented to children of primary schools. Stands in shopping centers were used in Palermo to distribute the regional vaccination schedule and gadgets, also providing indications on reliable websites where to find correct information on vaccinations. A music video played by health care workers (HCWs) was created and used in the University Hospital of Cagliari to promote the anti-flu vaccination campaign in HCWs. In Apulia, meetings with the general population were organized to collect controversial issues about vaccinations and a national call center was launched to create a direct line from the general population to experts in vaccines and vaccination strategies. In Veneto, meetings in the birth centers and home visits for subjects refusing vaccination have been organized. All activities are useful and effective tools to increase knowledge about VPID and confidence in vaccination, which are crucial aspects in order to increase vaccine uptake. The project was funded by the Italian Ministry of Health, Center for Disease Prevention and Control (CCM) in 2013.
Ni, Zhaohui; Chen, Yan; Ong, Edison; He, Yongqun
As one of the most influential and troublesome human pathogens, Acinetobacter baumannii (A. baumannii) has emerged with many multidrug-resistant strains. After collecting 33 complete A. baumannii genomes and 84 representative antibiotic resistance determinants, we used the Vaxign reverse vaccinology approach to predict classical type vaccine candidates against A. baumannii infections and new type vaccine candidates against antibiotic resistance. Our genome analysis identified 35 outer membrane or extracellular adhesins that are conserved among all 33 genomes, have no human protein homology, and have less than 2 transmembrane helices. These 35 antigens include 11 TonB dependent receptors, 8 porins, 7 efflux pump proteins, and 2 fimbrial proteins (FilF and CAM87009.1). CAM86003.1 was predicted to be an adhesin outer membrane protein absent from 3 antibiotic-sensitive strains and conserved in 21 antibiotic-resistant strains. Feasible anti-resistance vaccine candidates also include one extracellular protein (QnrA), 3 RND type outer membrane efflux pump proteins, and 3 CTX-M type β-lactamases. Among 39 β-lactamases, A. baumannii CTX-M-2, -5, and -43 enzymes are predicted as adhesins and better vaccine candidates than other β-lactamases to induce preventive immunity and enhance antibiotic treatments. This report represents the first reverse vaccinology study to systematically predict vaccine antigen candidates against antibiotic resistance for a microbial pathogen.
Full Text Available Abstract HPV vaccine is an exciting promise of the preventive medicine. Although HPV-immunization programs still reveal a number of unanswered questions, they represent a novel opportunity for primary prevention against cervical cancer and other HPV-related pre-neoplastic and neoplastic diseases. It is reasonable that the short and long-term benefits of vaccination on cervical and vulvo-vaginal HPV-related pathology will emerge when assuring over time a clear and complete information to the community and harmonizing the prevention strategies. Indeed, HPV-vaccination programs will require an understanding of new paradigms of infection and cancer control, and thus will require a rationale integration with the currently operating screening systems.
El Masry, Ihab; Rijks, Jolianne; Peyre, Marisa; Taylor, Nick; Lubroth, Juan; Jobre, Yilma
Highly pathogenic avian influenza (AI) due to H5N1 virus was first reported in Egypt in February 2006; since then, the government has allowed avian influenza vaccination in poultry. The present study evaluated the impact of AI vaccination in terms of cumulative annual flock immunity (CAFI): the percentage of bird × weeks protected by immunity. This evaluation took account of the combined effects of vaccination coverage, vaccine efficacy (VE), and different characteristics of household poultry production on the effectiveness of the adopted vaccination strategy (VS), and provided alternative options for improvement. The evaluation used a population and vaccination model that calculates the CAFI. Participatory approaches were employed in 21 villages to develop the vaccination and flock parameters required for the model. The adopted VS were compared in the model with three alternative VS scenarios in terms of the CAFI. Vaccination coverage varied among villages but was generally low (between 1 and 48 %; median 14 %). Under the adopted VS, the CAFI predicted for the villages ranged from 2 to 31 %. It was concluded that despite the enormous effort put into rural household poultry AI vaccination by the Egyptian government, village CAFI is unlikely to be maintained at the levels required to significantly reduce the virus load and restrict transmission. In HPAI-endemic countries that consider AI vaccination as one of the disease control options, the high cost of mass AI vaccination campaigns and their achievable benefits must be compared with other available control measures, which may include targeted vaccination. Achievable vaccination coverage, VE and the different characteristics of commercial and household (village) poultry production are key parameters determining the feasibility and cost-effectiveness of different AI vaccination strategies.
Chakraborty, Arup K.; Barton, John P.
Vaccination has saved more lives than any other medical procedure. Pathogens have now evolved that have not succumbed to vaccination using the empirical paradigms pioneered by Pasteur and Jenner. Vaccine design strategies that are based on a mechanistic understanding of the pertinent immunology and virology are required to confront and eliminate these scourges. In this perspective, we describe just a few examples of work aimed to achieve this goal by bringing together approaches from statistical physics with biology and clinical research.
Uddin, Mohammad Nasir; Kouzi, Samir A; Hussain, Muhammad Delwar
Human Papillomaviruses (HPV) are a diverse group of small non-enveloped DNA viruses. Some HPVs are classified as low-risk as they are very rarely associated with neoplasia or cancer in the general population, and cause lenient warts. Other HPVs are considered as high-risk types because they are responsible for several important human cancers, including cervical cancer, a large proportion of other anogenital cancers, and a growing number of head and neck cancers. Transmission of HPV occurs primarily by skin-to-skin contact. The risk of contracting genital HPV infection and cervical cancer is influenced by sexual activity. Currently two prophylactic HPV vaccines, Gardasil® (Merck, USA) and Cervarix® (GlaxoSmithKline, UK), are available and recommended for mass immunization of adolescents. However, these vaccines have limitations as they are expensive and require cold chain storage and trained personnel to administer them by injection. The use of nano or micro particulate vaccines could address most of these limitations as they are stable at room temperature, inexpensive to produce and distribute to resource poor regions, and can be administered orally without the need for adjuvants in the formulation. Also it is possible to increase the efficiency of these particulate vaccines by decorating the surface of the nano or micro particulates with suitable ligands for targeted delivery. Oral vaccines, which can be delivered using particulate formulations, have the added potential to stimulate mucosa-associated lymphoid tissue located in the digestive tract and the gut-associated lymphoid tissue, both of which are important for the induction of effective mucosal response against many viruses. In addition, oral vaccines provide the opportunity to reduce production and administration costs and are very patient compliant. This review elaborately discusses different strategies that can be pursued to develop a nano or micro particulate oral vaccine for HPV induced cancers and
The aim of the studies described in this thesis was to investigate the effi cacy of a therapeutic immunization strategy against cervical cancer and premalignant cervical disease. Cervical cancer is caused by persistent infection with high-risk human papillomavirus (HPV). Two of the early proteins of
Capripox is an important transboundary animal disease that is endemic across Africa, the Middle East, and some parts of Asia. The disease is highly contagious and considered to be a major obstacle causing significant economic loses in many agricultural areas. In this study, a mathematical model is developed to describe the transmission dynamics of capripoxvirus (CaPV) among livestock. This proposed model incorporates direct and indirect transmission of CaPV, together with two vaccination strategies, to investigate their effects on the severity of outbreaks and the prevalence of CaPV among the livestock population. The results suggest that ratio of potential vectors to livestock, successful probability of infection, vaccination rates, waning rate of vaccine-conferred protection, and virus introduction time play crucial roles in determining the outbreak severity and the prevalence level. The results also show that it is optimal to vaccinate newborns at the maximum effort throughout the control program and moderately increase vaccination rate for a susceptible pool to reach its maximum level after the outbreak. Copyright © 2017 Elsevier Ltd. All rights reserved.
Vashishtha, Vipin M; Choudhary, Jaydeep; Yadav, Sangeeta; Unni, Jeeson C; Jog, Pramod; Kamath, Sachidanand S; Sachdeva, Anupam; Srirampur, Sanjay; Prajapati, Baldev; Parekh, Bakul J
The World Health Organization declared India among other 10 countries in South East Region - as 'polio-free' in 2014. Since then, the Government of India (GoI) has scaled up its initiatives against polio endgame which targets virus eradication and sequential withdrawal of type 2 virus from oral polio vaccine (OPV). However, prior to choosing the switch from trivalent OPV (t-OPV) to bivalent OPV (b-OPV), it was suggested to include inactivated poliovirus vaccine (IPV) in the national immunization schedule to protect vaccine naïve population against type 2 poliovirus. The GoI declared introduction of single dose of intramuscular IPV at 14 weeks since October 2015. In addition, anticipating the scarcity of IPV at present in India, GoI also recommended two intradermal doses of IPV in few states since April 2016. This review discusses the programmatic implications of these strategies along with recommendations by the Advisory Committee on Vaccines and Immunization Practices of Indian Academy of Pediatrics (IAP-ACVIP) on polio endgame strategy.
With the significant enrollment increase of English Language Learners (ELLs) nationwide, social studies teachers face challenges to educate these students. As a response to the literature of preparing all content teachers to work with ELLs, this article introduces three teacher-friendly language-focused strategies. These strategies help social…
Harmsen, I.A.; Bos, H.; Ruiter, R.A.C.; Paulussen, T.G.W.; Kok, G.; Melker, H.E. de; Mollema, L.
Background Although the vaccination coverage in most high income countries is high, variations in coverage rates on the national level among different ethnic backgrounds are reported. A qualitative study was performed to explore factors that influence decision-making among parents with different
Bonhoeffer, Jan; Imoukhuede, Egeruan B; Aldrovandi, Grace; Bachtiar, Novilia S.; Chan, Eng-Soon; Chang, Soju; Chen, Robert T.; Fernandopulle, Rohini; Goldenthal, Karen L.; Heffelfinger, James D.; Hossain, Shah; Jevaji, Indira; Khamesipour, Ali; Kochhar, Sonali; Makhene, Mamodikoe
This document is intended as a guide to the protocol development for trials of prophylactic vaccines. The template may serve phases I–IV clinical trials protocol development to include safety relevant information as required by the regulatory authorities and as deemed useful by the investigators. This document may also be helpful for future site strengthening efforts.
Although dental caries is a global problem in modern times, no vaccines are available for preventing these diseases. Among the bacterial pathogens that cause dental caries, including Streptococcus mutans, S. sobrinus, and Lactobacillus acidophilus, and Actinomyces viscosus, S. mutans is the most prominent and prevalent species. During the past, much effort has been focused on developing vaccines against S. mutans. Early attempts used fixed whole cells of S. mutans, but later it was found that serological cross-reactivity between heart tissue antigens and Streptococcus antigens occurs in patients resulting in rheumatic fever. Recently, with the aid of molecular biology, the genome sequences of S. mutans strains are available, which can greatly accelerate the development of subunit vaccines. Many desirable candidate subunit vaccines have been or are going to be evaluated in either experimental animal models or in human clinical trials. In this review article, we summarized the updated progress made in deciphering the mechanisms of disease development and the achievements of vaccine research against S. mutans.
Tsuda, Yuko; Watanabe, Misuzu; Tanimoto, Yoshimi; Hayashida, Itsushi; Kusabiraki, Toshiyuki; Komiyama, Maki; Kono, Koichi
This study aimed to understand the current scenario of voluntary vaccination and the factors influencing its coverage among 18-month-old children of Takatsuki City, Japan. Based on 1167 parents responses, we found that voluntary vaccination coverage rates were low when compared with routine vaccination rates. The children who were not the first born of the family and who had young and poorly educated parents were less likely to receive voluntary vaccination. Japanese government-supported vaccines, such as Haemophilus influenzae type b and pneumococcal vaccine, had a higher coverage than the vaccines for which parents had to bear the entire vaccination cost. Furthermore, it was found that mass communication media and family pediatricians were effective means to disseminate voluntary vaccination-related information. We envisage that an active participation of medical professionals, easy access to vaccinations, and mass awareness programs will increase voluntary vaccination coverage in Takatsuki. © 2013 APJPH.
Full Text Available BACKGROUND: Prior economic evaluations of adult and adolescent vaccination strategies against pertussis have reached disparate conclusions. Using static approaches only, previous studies failed to analytically include the indirect benefits derived from herd immunity as well as the impact of vaccination on the evolution of disease incidence over time. METHODS: We assessed the impact of different pertussis vaccination strategies using a dynamic compartmental model able to consider pertussis transmission. We then combined the results with economic data to estimate the relative cost-effectiveness of pertussis immunization strategies for adolescents and adults in the US. The analysis compares combinations of programs targeting adolescents, parents of newborns (i.e. cocoon strategy, or adults of various ages. RESULTS: In the absence of adolescent or adult vaccination, pertussis incidence among adults is predicted to more than double in 20 years. Implementing an adult program in addition to childhood and adolescent vaccination either based on 1 a cocoon strategy and a single booster dose or 2 a decennial routine vaccination would maintain a low level of pertussis incidence in the long run for all age groups (respectively 30 and 20 cases per 100,000 person years. These strategies would also result in significant reductions of pertussis costs (between -77% and -80% including additional vaccination costs. The cocoon strategy complemented by a single booster dose is the most cost-effective one, whereas the decennial adult vaccination is slightly more effective in the long run. CONCLUSIONS: By providing a high level of disease control, the implementation of an adult vaccination program against pertussis appears to be highly cost-effective and often cost-saving.
McQuaid, Fiona; Pask, Sophie; Locock, Louise; Davis, Elizabeth; Stevens, Zoe; Plumb, Jane; Snape, Matthew D
Antenatal vaccination has become a part of routine care during pregnancy in the UK and worldwide, leading to improvements in health for both pregnant women and their infants. However, uptake remains sub-optimal. Other antenatal vaccines targeting major neonatal pathogens, such as Group B streptococcus (GBS), the commonest cause of sepsis and meningitis in the neonatal period, are undergoing clinical trials but more information is needed on how to improve acceptance of such vaccines. Qualitative study using focus groups and interviews; involving 14 pregnant women, 8 mothers with experience of GBS, and 28 maternity healthcare professionals. Questions were asked regarding antenatal vaccines, knowledge of GBS, attitudes to a potential future GBS vaccine and participation in antenatal vaccine trials. All participants were very cautious about vaccination during pregnancy, with harm to the baby being a major concern. Despite this, the pregnant women and parents with experience of GBS were open to the idea of an antenatal GBS vaccine and participating in research, while the maternity professionals were less positive. Major barriers identified included lack of knowledge about GBS and the reluctance of maternity professionals to be involved. In order for a future GBS vaccine to be acceptable to both pregnant women and the healthcare professionals advising them, a major awareness campaign would be required with significant focus on convincing and training maternity professionals. Copyright © 2016 Elsevier Ltd. All rights reserved.
Full Text Available The IT field, by its nature and evolution, requires a special attention to the online communication strategy. If for most IT companies, the marketing strategy is customized according to their product, customers, marketing objectives, budget, marketing team size, etc., there is a common perception of the digital communication strategy. Therefore, this article, which is based on two Focus-group research projects, aims to present the attitudes, experiences and opinions of online marketers related to the digital communication strategy of the IT companies based in Romania.
Bonhoeffer, Jan; Imoukhuede, Egeruan B; Aldrovandi, Grace; Bachtiar, Novilia S; Chan, Eng-Soon; Chang, Soju; Chen, Robert T; Fernandopulle, Rohini; Goldenthal, Karen L; Heffelfinger, James D; Hossain, Shah; Jevaji, Indira; Khamesipour, Ali; Kochhar, Sonali; Makhene, Mamodikoe; Malkin, Elissa; Nalin, David; Prevots, Rebecca; Ramasamy, Ranjan; Sellers, Sarah; Vekemans, Johan; Walker, Kenneth B; Wilson, Pam; Wong, Virginia; Zaman, Khalequz; Heininger, Ulrich
This document is intended as a guide to the protocol development for trials of prophylactic vaccines. The template may serve phases I-IV clinical trials protocol development to include safety relevant information as required by the regulatory authorities and as deemed useful by the investigators. This document may also be helpful for future site strengthening efforts. Copyright © 2013 Elsevier Ltd. All rights reserved.
Stanisic, Danielle I; Good, Michael F
Despite a century of research focused on the development and implementation of effective control strategies, infection with the malaria parasite continues to result in significant morbidity and mortality worldwide. An effective malaria vaccine is considered by many to be the definitive solution. Yet, after decades of research, we are still without a vaccine that is capable of inducing robust, long lasting protection in naturally exposed individuals. Extensive sub-unit vaccine development focused on the blood stage of the malaria parasite has thus far yielded disappointing results. There is now a renewed focus on whole parasite vaccine strategies, particularly as they may overcome some of the inherent weaknesses deemed to be associated with the sub-unit approach. This review discusses the whole parasite vaccine strategy focusing on the blood stage of the malaria parasite, with an emphasis on recent advances and challenges in the development of killed and live attenuated vaccines. Copyright © 2015 Elsevier Ltd. All rights reserved.
Aswathyraj, S; Arunkumar, G; Alidjinou, E K; Hober, D
Hand, foot, and mouth disease (HFMD) is a contagious viral disease and mainly affects infants and young children. The main manifestations are fever, vesicular rashes on hand, feet and buttocks and ulcers in the oral mucosa. Usually, HFMD is self-limiting, but a small proportion of children may experience severe complications such as meningitis, encephalitis, acute flaccid paralysis and neurorespiratory syndrome. Historically, outbreaks of HFMD were mainly caused by two enteroviruses: the coxsackievirus A16 (CV-A16) and the enterovirus 71 (EV-A71). In the recent years, coxsackievirus A6 and coxsackievirus A10 have been widely associated with both sporadic cases and outbreaks of HFMD worldwide, particularly in India, South East Asia and Europe with an increased frequency of neurological complications as well as mortality. Currently, there is no pharmacological intervention or vaccine available for HFMD. A formalin-inactivated EV-A71 vaccine has completed clinical trial in several Asian countries. However, this vaccine cannot protect against other major emerging etiologies of HFMD such as CV-A16, CV-A6 and CV-A10. Therefore, the development of a globally representative multivalent HFMD vaccine could be the best strategy.
Smith, Jennifer C; Appleton, Mary; MacDonald, Noni E
Despite significant efforts by governments, organizations and individuals to maintain public trust in vaccines, concerns persist and threaten to undermine the effectiveness of immunization programs. Vaccine advocates have traditionally focused on education based on evidence to address vaccine concerns and hesitancy. However, being informed of the facts about immunization does not always translate into support for immunization. While many are persuaded by scientific evidence, others are more influenced by cognitive shortcuts, beliefs, societal pressure and the media, with the latter group more likely to hesitate over immunization. Understanding evidence from the behaviour sciences opens new doors to better support individual decision-making about immunization. Drawing on heuristics, this overview explores how individuals find, process and utilize vaccine information and the role health care professionals and society can play in vaccine decision-making. Traditional, evidence-based approaches aimed at staunching the erosion of public confidence in vaccines are proving inadequate and expensive. Enhancing public confidence in vaccines will be complex, necessitating a much wider range of strategies than currently used. Success will require a shift in how the public, health care professionals and media are informed and educated about vaccine benefits, risks and safety; considerable introspection and change in current academic and vaccine decision-making practices; development of proactive strategies to broadly address current and potential future concerns, as well as targeted interventions such as programs to address pain with immunization. This overview outlines ten such opportunities for change to improve vaccine confidence.
Geels, Mark J; Imoukhuede, Egeruan B; Imbault, Nathalie; van Schooten, Harry; McWade, Terry; Troye-Blomberg, Marita; Dobbelaer, Roland; Craig, Alister G; Leroy, Odile
For over 10 years, the European Vaccine Initiative (EVI; European Malaria Vaccine Initiative until 2009) has contributed to the development of 24 malaria candidate vaccine antigens with 13 vaccine candidates being advanced into Phase I clinical trials, two of which have been transitioned for further clinical development in sub-Saharan Africa. Since its inception the EVI organization has operated as a funding agency, but with a clear service-oriented strategy. The scientific successes and difficulties encountered during these years and how these efforts have led to standardization and harmonization in vaccine development through large-scale European consortia are discussed. In the future, the EVI will remain instrumental in the pharmaceutical and clinical development of vaccines against 'diseases of poverty' with a continued focus on malaria. EVI will continue to focus on funding and managing preclinical evaluation up to Phase I/II clinical trials and strengthening the vaccine-development infrastructure in Europe, albeit with a global orientation.
McReynolds, Sara W; Sanderson, Michael W; Reeves, Aaron; Hill, Ashley E
The central United States (U.S.) has a large livestock population including cattle, swine, sheep and goats. Simulation models were developed to assess the impact of livestock herd types and vaccination on foot and mouth disease (FMD) outbreaks using the North American Animal Disease Spread Model. In this study, potential FMD virus outbreaks in the central region of the U.S. were simulated to compare different vaccination strategies to a depopulation only scenario. Based on data from the U.S. Department of Agriculture National Agricultural Statistics Service, a simulated population of 151,620 livestock operations characterized by latitude and longitude, production type, and herd size was generated. For the simulations, a single 17,000 head feedlot was selected as the initial latently infected herd in an otherwise susceptible population. Direct and indirect contact rates between herds were based on survey data of livestock producers in Kansas and Colorado. Control methods included ring vaccination around infected herds. Feedlots ≥3000 head were either the only production type that was vaccinated or were assigned the highest vaccination priority. Simulated vaccination scenarios included low and high vaccine capacity, vaccination zones of 10 km or 50 km around detected infected premises, and vaccination trigger of 10 or 100 detected infected herds. Probability of transmission following indirect contact, movement controls and contact rate parameters were considered uncertain and so were the subjects of sensitivity analysis. All vaccination scenarios decreased number of herds depopulated but not all decreased outbreak duration. Increased size of the vaccination zone during an outbreak decreased the length of the outbreak and number of herds destroyed. Increased size of the vaccination zone primarily resulted in vaccinating feedlots ≥3000 head across a larger area. Increasing the vaccination capacity had a smaller impact on the outbreak and may not be feasible if
Henrich, N; Holmes, B
As influenza H1N1 spreads around the world, health officials are considering the development and use of a new vaccine to protect the public and help control the outbreak. Acceptance of novel vaccines during health crises, however, is influenced by perceptions of a range of risks, including the risk of infection, risk of becoming severely ill or dying if infected, as well as the risk of serious side and long-term effects of the vaccine. A study on 11 focus groups was conducted with the public in Vancouver, Canada in 2006 and 2007 to explore how people assess these risks and how these assessments relate to their willingness to use novel vaccines in a pandemic. Concerns about using new vaccines during a pandemic differ from concerns about using established products in a non-crisis situation. Participants were hesitant to use novel vaccines because of a low perception of the early risk of infection in a pandemic, coupled with the many uncertainties that surround new vaccines and the emerging infectious disease, and owing to the concern that unsafe pharmaceuticals may be rushed to market during a health crisis. Understanding the public´s assessment of the risks related to, and willingness to use, novel vaccines during a pandemic can help officials promote disease-control measures in ways that improve the likelihood of acceptance by the public and may increase uptake of an H1N1 vaccine.
... disease — reinforcing the importance of vaccines in your pet's preventive health care program. Are there risks? Any treatment carries some risk, but these risks should be weighed against the benefits of protecting your pet from potentially fatal diseases. ...
Gröessler, Andreas; Laugen, Bjørge Timenes; Lassen, Astrid Heidemann
The purpose of this paper is to investigate the extent to which continuous innovation is pursued as a strategy for manufacturing firms in different types of competitive environments, and whether continuous innovation firms perform better than focused firms in certain environments. Statistical...... analyses are used of data collected from an international sample of manufacturing firms through the International Manufacturing Strategy Survey. The main findings are that, while focused as well as continuous innovation firms exist in all three types of business environments identified in this paper...
Li, Fangjun; Hu, Yuansheng; Zhou, Youming; Chen, Lixin; Xia, Wei; Song, Yufei; Tan, Zhengliang; Gao, Lidong; Yang, Zhong; Zeng, Gang; Han, Xing; Li, Junhua; Li, Jing
Booster doses could play a major role in no responders or low responders to primary hepatitis B (HB) vaccine. Planed time point for hepatitis A vaccination in China provides a good opportunity to carry out HB booster dose by using combined hepatitis A and B vaccine. A randomized, double-blinded clinical trial was conducted to compare the immunogenicity and safety of toddlers 18-24 months of age receiving 3 different vaccination regimens: 2 doses of inactivated hepatitis A vaccine (group 1), 1 dose of inactivated hepatitis A vaccine plus 1 dose of combined hepatitis A and B vaccine (group 2) or 2 doses of combined hepatitis A and B vaccine (group 3). All 3 groups showed 100% seroprotection for antihepatitis A virus antibody after vaccination. Seroprotection rate for anti-HB antibody before vaccination ranged from 79.5% to 92.9% in the 3 groups. After second inoculation, anti-HBs seroprotection increased from 92.9% to 100% in group 2 with postvaccination geometric mean concentration (GMC) of 2258.3 mIU/mL and from 79.5% to 98.9% in group 3 with postvaccination GMC of 2055.3 mIU/mL. The adverse events were not statistically different among groups (P = 0.345). Combined hepatitis A and B vaccine could stimulate high level of both antihepatitis A virus and anti-HBs antibodies and not increase adverse events, providing a new choice for HB booster.
Karachaliou, Andromachi; Conlan, Andrew J K; Preziosi, Marie-Pierre; Trotter, Caroline L
The introduction of MenAfriVac in campaigns targeting people aged 1-29 years across the African meningitis belt has successfully reduced meningitis incidence and carriage due to Neisseria meningitidis group A (MenA). It is important to consider how best to sustain population protection in the long term. We created a mathematical model of MenA transmission and disease to investigate the potential impact of a range of immunization strategies. The model is age structured; includes classes of susceptible, carrier, ill, and immune people (who may be vaccinated or unvaccinated); and incorporates seasonal transmission and a stochastic forcing term that models between year variation in rates of transmission. Model parameters were primarily derived from African sources. The model can describe the typical annual incidence of meningitis in the prevaccine era, with irregular epidemics of varying size. Parameter and structural uncertainty were explored in sensitivity analyses. Following MenAfriVac introduction at high uptake, the model predicts excellent short-term disease control. With no subsequent immunization, strong resurgences in disease incidence were predicted after approximately 15 years (assuming 10 years' average vaccine protection). Routine immunization at 9 months of age resulted in lower average annual incidence than regular mass campaigns of 1- to 4-year-olds, provided coverage was above approximately 60%. The strategy with the lowest overall average annual incidence and longest time to resurgence was achieved using a combination strategy of introduction into the Expanded Programme on Immunization at 9 months, 5 years after the initial mass campaigns, with a catch-up targeting unvaccinated 1- to 4-year-olds. These results can be used to inform policy recommendations for long-term vaccination strategies with MenAfriVac. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.
Duintjer Tebbens, Radboud J; Pallansch, Mark A; Wassilak, Steven G F; Cochi, Stephen L; Thompson, Kimberly M
Following successful eradication of wild polioviruses and planned globally-coordinated cessation of oral poliovirus vaccine (OPV), national and global health leaders may need to respond to outbreaks from reintroduced live polioviruses, particularly vaccine-derived polioviruses (VDPVs). Preparing outbreak response plans and assessing potential vaccine needs from an emergency stockpile require consideration of the different national risks and conditions as they change with time after OPV cessation. We used an integrated global model to consider several key issues related to managing poliovirus risks and outbreak response, including the time interval during which monovalent OPV (mOPV) can be safely used following homotypic OPV cessation; the timing, quality, and quantity of rounds required to stop transmission; vaccine stockpile needs; and the impacts of vaccine choices and surveillance quality. We compare the base case scenario that assumes aggressive outbreak response and sufficient mOPV available from the stockpile for all outbreaks that occur in the model, with various scenarios that change the outbreak response strategies. Outbreak response after OPV cessation will require careful management, with some circumstances expected to require more and/or higher quality rounds to stop transmission than others. For outbreaks involving serotype 2, using trivalent OPV instead of mOPV2 following cessation of OPV serotype 2 but before cessation of OPV serotypes 1 and 3 would represent a good option if logistically feasible. Using mOPV for outbreak response can start new outbreaks if exported outside the outbreak population into populations with decreasing population immunity to transmission after OPV cessation, but failure to contain outbreaks resulting in exportation of the outbreak poliovirus may represent a greater risk. The possibility of mOPV use generating new long-term poliovirus excretors represents a real concern. Using the base case outbreak response assumptions, we
Sheahan, Timothy; Whitmore, Alan; Long, Kristin; Ferris, Martin; Rockx, Barry; Funkhouser, William; Donaldson, Eric; Gralinski, Lisa; Collier, Martha; Heise, Mark; Davis, Nancy; Johnston, Robert; Baric, Ralph S
Newly emerging viruses often circulate as a heterogeneous swarm in wild animal reservoirs prior to their emergence in humans, and their antigenic identities are often unknown until an outbreak situation. The newly emerging severe acute respiratory syndrome coronavirus (SARS-CoV) and reemerging influenza virus cause disproportionate disease in the aged, who are also notoriously difficult to successfully vaccinate, likely due to immunosenescence. To protect against future emerging strains, vaccine platforms should induce broad cross-reactive immunity that is sufficient to protect from homologous and heterologous challenge in all ages. From initial studies, we hypothesized that attenuated Venezuelan equine encephalitis virus (VEE) replicon particle (VRP) vaccine glycoproteins mediated vaccine failure in the aged. We then compared the efficacies of vaccines bearing attenuated (VRP(3014)) or wild-type VEE glycoproteins (VRP(3000)) in young and aged mice within novel models of severe SARS-CoV pathogenesis. Aged animals receiving VRP(3000)-based vaccines were protected from SARS-CoV disease, while animals receiving the VRP(3014)-based vaccines were not. The superior protection for the aged observed with VRP(3000)-based vaccines was confirmed in a lethal influenza virus challenge model. While the VRP(3000) vaccine's immune responses in the aged were sufficient to protect against lethal homologous and heterologous challenge, our data suggest that innate defects within the VRP(3014) platform mediate vaccine failure. Exploration into the mechanism(s) of successful vaccination in the immunosenescent should aid in the development of successful vaccine strategies for other viral diseases disproportionately affecting the elderly, like West Nile virus, influenza virus, norovirus, or other emerging viruses of the future.
The objective of this study was to determine if Learning-Focused Strategies (LFS) implemented in high school science courses would affect student achievement and the pass rate of biology and physical science Common District Assessments (CDAs). The LFS, specific teaching strategies contained in the Learning-Focused Strategies Model (LFSM) Program were researched in this study. The LFSM Program provided a framework for comprehensive school improvement to those schools that implemented the program. The LFSM Program provided schools with consistent training in the utilization of exemplary practices and instruction. A high school located in the suburbs of Atlanta, Georgia was the focus of this investigation. Twelve high school science classrooms participated in the study: six biology and six physical science classes. Up-to-date research discovered that the strategies contained in the LFSM Program were research-based and highly effective for elementary and middle school instruction. Research on its effectiveness in high school instruction was the main focus of this study. This investigation utilized a mixed methods approach, in which data were examined qualitatively and quantitatively. Common District Assessment (CDA) quantitative data were collected and compared between those science classrooms that utilized LFS and those using traditional instructional strategies. Qualitative data were generated through classroom observations, student surveys, and teacher interviews. Individual data points were triangulated to determine trends of information reflecting the effects of implementing LFS. Based on the data collected in the research study, classrooms utilizing LFS were more successful academically than the classrooms using traditional instructional methods. Derived from the quantitative data, students in LFS classrooms were more proficient on both the biology and physical science Unit 1 CDAs, illustrating the effectiveness of LFS in the science classroom. Key terms
Fraiz, Lauren Dapena; de Roche, Ariel; Mauro, Christine; Catallozzi, Marina; Zimet, Gregory D; Shapiro, Gilla K; Rosenthal, Susan L
Zika virus infection during pregnancy can cause significant infant morbidity. Little is known about pregnant women's attitudes regarding behavioral strategies and hypothetical vaccination to prevent Zika infections and sequelae. Pregnant women across the United States (N = 362) completed an online questionnaire regarding attitudes about Zika, including six behavioral prevention strategies (i.e., abstaining from sex, using condoms, not traveling to an area with Zika, their partner not traveling into an area with Zika, using mosquito repellant, wearing long pants and sleeves) and vaccination. Most women (91%) were married/living with the baby's father, 65% were non-Hispanic White, and 71% had been pregnant. Seventy-four percent were worried about Zika, while 30% thought they were knowledgeable about Zika. The mean knowledge score was 5.0 out of 8 (SD = 2.09), and the mean behavioral strategies score was 4.9 out of 12 (SD = 3.7) with a range of 0 (none would be hard to do) to 12 (all would be hard to do). In a multivariable model, having had a sexually transmitted infection, living/traveling in an area with Zika, and worrying about Zika were significantly related to reporting behavioral strategies as hard to do. Seventy-two percent would be willing to be vaccinated. In the multivariable model, living/traveling in an area with Zika, believing they knew a lot about Zika, worrying about Zika, and considering Zika vaccine development as important were significantly associated with willingness to get vaccinated. Pregnant women were worried about Zika, yet had gaps in their factual knowledge. Most women reported they would get vaccinated if a vaccine was available. Pregnant women who reported themselves as vulnerable (being worried, having lived in or traveled to a Zika area) were more likely to view behavioral strategies as hard to do and to accept vaccination. Copyright © 2017. Published by Elsevier Ltd.
Brunton, James; Brown, Mark; Costello, Eamon; Walsh, Elaine
This case study describes the process that the Humanities Programme Team, in Dublin City University's Open Education Unit, has undertaken with regard to developing a systematic, programme-focused assessment strategy. It charts the development of an Assessment Matrix that facilitated the enhancement of programme coherence in the context of a…
Uttenthal, Åse; Parida, Satya; Rasmussen, Thomas Bruun
The prophylactic use of vaccines against exotic viral infections in production animals is undertaken exclusively in regions where the disease concerned is endemic. In such areas, the infection pressure is very high and so, to assure optimal protection, the most efficient vaccines are used. However......, in areas considered to be free from these diseases and in which there is the possibility of only limited outbreaks, the use of Differentiation of Infected from Vaccinated Animals (DIVA) or marker vaccines allows for vaccination while still retaining the possibility of serological surveillance...... for the presence of infection. This literature review describes the current knowledge on the use of DIVA diagnostic strategies for three important transboundary animal diseases: foot-and-mouth disease in cloven-hoofed animals, classical swine fever in pigs and avian influenza in poultry....
with rotavirus are higher than with HPV since both genders are vaccinated. Conclusions While lifesaving benefits of rotavirus and HPV vaccines will be realized at different times, the number of lives saved over each target populations' lifetimes will be similar. Model-based analyses that use a standardized analytic approach and generate comparable outputs can enrich the priority-setting dialogue. Although new vaccines may be deemed cost-effective, other factors including affordability and distributional equity need to be considered in different settings. We caution that for priority setting in an individual country, more rigorous comparisons should be performed, using more comprehensive models and considering all relevant vaccines and delivery strategies.
Kim, Sun-Young; Sweet, Steven; Chang, Joshua; Goldie, Sue J
genders are vaccinated. While lifesaving benefits of rotavirus and HPV vaccines will be realized at different times, the number of lives saved over each target populations' lifetimes will be similar. Model-based analyses that use a standardized analytic approach and generate comparable outputs can enrich the priority-setting dialogue. Although new vaccines may be deemed cost-effective, other factors including affordability and distributional equity need to be considered in different settings. We caution that for priority setting in an individual country, more rigorous comparisons should be performed, using more comprehensive models and considering all relevant vaccines and delivery strategies.
Full Text Available The purpose of this article, which can be envision as an essay, is to present a pedagogical-didactic strategy for human rights education focusing on the controversy. Advancements and setbacks faced by human rights education in Latin America are exposed in order to support this strategy. Therefore, it indicates that education has denied the conflict and explains the need for its inclusion under the idea of ‘controversial issue’. Additionally, the existence of conflicts in the interpretation, violation and/or respect for human rights is pointed out. The principal tensions that cross human rights are displayed. Based on the above, the need to support the existence of a human rights education focusing on the conflict and central components of its teaching strategy are described, and it ends by referring to its didactic approach and the role which should be assumed by faculty when teaching human rights including the conflict.
Fan Du; Shneiderman, Ben; Plaisant, Catherine; Malik, Sana; Perer, Adam
The growing volume and variety of data presents both opportunities and challenges for visual analytics. Addressing these challenges is needed for big data to provide valuable insights and novel solutions for business, security, social media, and healthcare. In the case of temporal event sequence analytics it is the number of events in the data and variety of temporal sequence patterns that challenges users of visual analytic tools. This paper describes 15 strategies for sharpening analytic focus that analysts can use to reduce the data volume and pattern variety. Four groups of strategies are proposed: (1) extraction strategies, (2) temporal folding, (3) pattern simplification strategies, and (4) iterative strategies. For each strategy, we provide examples of the use and impact of this strategy on volume and/or variety. Examples are selected from 20 case studies gathered from either our own work, the literature, or based on email interviews with individuals who conducted the analyses and developers who observed analysts using the tools. Finally, we discuss how these strategies might be combined and report on the feedback from 10 senior event sequence analysts.
Choi, K. Yeon; Root, Matthew
ABSTRACT Congenital cytomegalovirus (CMV) infection is a leading cause of mental retardation and deafness in newborns. The guinea pig is the only small animal model for congenital CMV infection. A novel CMV vaccine was investigated as an intervention strategy against congenital guinea pig cytomegalovirus (GPCMV) infection. In this disabled infectious single-cycle (DISC) vaccine strategy, a GPCMV mutant virus was used that lacked the ability to express an essential capsid gene (the UL85 homolog GP85) except when grown on a complementing cell line. In vaccinated animals, the GP85 mutant virus (GP85 DISC) induced an antibody response to important glycoprotein complexes considered neutralizing target antigens (gB, gH/gL/gO, and gM/gN). The vaccine also generated a T cell response to the pp65 homolog (GP83), determined via a newly established guinea pig gamma interferon enzyme-linked immunosorbent spot assay. In a congenital infection protection study, GP85 DISC-vaccinated animals and a nonvaccinated control group were challenged during pregnancy with wild-type GPCMV (105 PFU). The pregnant animals carried the pups to term, and viral loads in target organs of pups were analyzed. Based on live pup births in the vaccinated and control groups (94.1% versus 63.6%), the vaccine was successful in reducing mortality (P = 0.0002). Additionally, pups from the vaccinated group had reduced CMV transmission, with 23.5% infected target organs versus 75.9% in the control group. Overall, these preliminary studies indicate that a DISC CMV vaccine strategy has the ability to induce an immune response similar to that of natural virus infection but has the increased safety of a non-replication-competent virus, which makes this approach attractive as a CMV vaccine strategy. IMPORTANCE Congenital CMV infection is a leading cause of mental retardation and deafness in newborns. An effective vaccine against CMV remains an elusive goal despite over 50 years of CMV research. The guinea pig, with
Raviotta, Jonathan M; Smith, Kenneth J; DePasse, Jay; Brown, Shawn T; Shim, Eunha; Nowalk, Mary Patricia; Wateska, Angela; France, Glenson S; Zimmerman, Richard K
High-dose trivalent inactivated influenza vaccine (HD-IIV3) or recombinant trivalent influenza vaccine (RIV) may increase influenza vaccine effectiveness (VE) in adults with conditions that place them at high risk for influenza complications. This analysis models the public health impact and cost-effectiveness (CE) of these vaccines for 50-64year-olds. Markov model CE analysis compared 5 strategies in 50-64year-olds: no vaccination; only standard-dose IIV3 offered (SD-IIV3 only), only quadrivalent influenza vaccine offered (SD-IIV4 only); high-risk patients receiving HD-IIV3, others receiving SD-IIV3 (HD-IIV3 & SD-IIV3); and high-risk patients receiving HD-IIV3, others receiving SD-IIV4 (HD-IIV3 & SD-IIV4). In a secondary analysis, RIV replaced HD-IIV3. Parameters were obtained from U.S. databases, the medical literature and extrapolations from VE estimates. Effectiveness was measured as 3%/year discounted quality adjusted life year (QALY) losses avoided. The least expensive strategy was SD-IIV3 only, with total costs of $99.84/person. The SD-IIV4 only strategy cost an additional $0.91/person, or $37,700/QALY gained. The HD-IIV3 & SD-IIV4 strategy cost $1.06 more than SD-IIV4 only, or $71,500/QALY gained. No vaccination and HD-IIV3 & SD-IIV3 strategies were dominated. Results were sensitive to influenza incidence, vaccine cost, standard-dose VE in the entire population and high-dose VE in high-risk patients. The CE of RIV for high-risk patients was dependent on as yet unknown parameter values. Based on available data, using high-dose influenza vaccine or RIV in middle-aged, high-risk patients may be an economically favorable vaccination strategy with public health benefits. Clinical trials of these vaccines in this population may be warranted. Copyright © 2017 Elsevier Ltd. All rights reserved.
Paris, Robert M; Kim, Jerome H; Robb, Merlin L; Michael, Nelson L
Challenges in the development of an effective HIV-1 vaccine are myriad with significant hurdles posed by viral diversity, the lack of a human correlate of protection and difficulty in creating immunogens capable of eliciting broadly neutralizing antibodies. The implicit requirement for novel approaches to these problems has resulted in vaccine candidates designed to elicit cellular and/or humoral immune responses, to include recombinant DNA, viral and bacterial vectors, and subunit proteins. Here, we review data from clinical studies primarily of poxvirus and adenovirus vector vaccines, used in a heterologous prime-boost combination strategy. Currently, this strategy appears to hold the most promise for an effective vaccine based on results from immunogenicity testing and nonhuman primate challenge models, as well as the modest efficacy recently observed in the Thai prime-boost trial.
Rawool, Deepak B.; Bitsaktsis, Constantine; Li, Ying; Gosselin, Diane R.; Lin, Yili; Kurkure, Nitin V.; Metzger, Dennis W.; Gosselin, Edmund J.
Numerous studies have demonstrated that targeting Ag to Fc receptors (FcR) on APCs can enhance humoral and cellular immunity. However, studies are lacking that examine both the use of FcR-targeting in generating immune protection against infectious agents and the use of FcRs in the induction of mucosal immunity. Francisella tularensis is a category A intracellular mucosal pathogen. Thus, intense efforts are underway to develop a vaccine against this organism. We hypothesized that protection against mucosal infection with F. tularensis would be significantly enhanced by targeting inactivated F. tularensis live vaccine strain (iFt) to FcRs at mucosal sites, via intranasal immunization with mAb-iFt complexes. These studies demonstrate for the first time that: 1) FcR-targeted immunogen enhances immunogen-specific IgA production and protection against subsequent infection in an IgA-dependent manner, 2) FcγR and neonatal FcR are crucial to this protection, and 3) inactivated F. tularensis, when targeted to FcRs, enhances protection against the highly virulent SchuS4 strain of F. tularensis, a category A biothreat agent. In summary, these studies show for the first time the use of FcRs as a highly effective vaccination strategy against a highly virulent mucosal intracellular pathogen. PMID:18390739
Maya F Kotturi
Full Text Available Arenaviruses are the causative pathogens of severe hemorrhagic fever and aseptic meningitis in humans, for which no licensed vaccines are currently available. Pathogen heterogeneity within the Arenaviridae family poses a significant challenge for vaccine development. The main hypothesis we tested in the present study was whether it is possible to design a universal vaccine strategy capable of inducing simultaneous HLA-restricted CD8+ T cell responses against 7 pathogenic arenaviruses (including the lymphocytic choriomeningitis, Lassa, Guanarito, Junin, Machupo, Sabia, and Whitewater Arroyo viruses, either through the identification of widely conserved epitopes, or by the identification of a collection of epitopes derived from multiple arenavirus species. By inoculating HLA transgenic mice with a panel of recombinant vaccinia viruses (rVACVs expressing the different arenavirus proteins, we identified 10 HLA-A02 and 10 HLA-A03-restricted epitopes that are naturally processed in human antigen-presenting cells. For some of these epitopes we were able to demonstrate cross-reactive CD8+ T cell responses, further increasing the coverage afforded by the epitope set against each different arenavirus species. Importantly, we showed that immunization of HLA transgenic mice with an epitope cocktail generated simultaneous CD8+ T cell responses against all 7 arenaviruses, and protected mice against challenge with rVACVs expressing either Old or New World arenavirus glycoproteins. In conclusion, the set of identified epitopes allows broad, non-ethnically biased coverage of all 7 viral species targeted by our studies.
Ma, Barbara; Maraj, Bharat; Tran, Nam Phuong; Knoff, Jayne; Chen, Alexander; Alvarez, Ronald D; Hung, Chien-Fu; Wu, T.-C.
Introduction Identification of human papillomavirus (HPV) as the etiologic factor of cervical, anogenital, and a subset of head and neck cancers has stimulated the development of preventive and therapeutic HPV vaccines to control HPV-associated malignancies. Excitement has been generated by the commercialization of two preventive L1-based vaccines, which use HPV virus-like particles (VLPs) to generate capsid-specific neutralizing antibodies. However, factors such as high cost and requirement for cold chain have prevented widespread implementation where they are needed most. Areas covered Next generation preventive HPV vaccine candidates have focused on cost-effective stable alternatives and generating broader protection via targeting multivalent L1 VLPs, L2 capsid protein, and chimeric L1/L2 VLPs. Therapeutic HPV vaccine candidates have focused on enhancing T cell-mediated killing of HPV-transformed tumor cells, which constitutively express HPV-encoded proteins, E6 and E7. Several therapeutic HPV vaccines are in clinical trials. Expert opinion Although progress is being made, cost remains an issue inhibiting the use of preventive HPV vaccines in countries that carry the majority of the cervical cancer burden. In addition, progression of therapeutic HPV vaccines through clinical trials may require combination strategies employing different therapeutic modalities. As research in the development of HPV vaccines continues, we may generate effective strategies to control HPV-associated malignancies. PMID:23163511
Larson, Heidi J; Jarrett, Caitlin; Eckersberger, Elisabeth; Smith, David M D; Paterson, Pauline
Vaccine "hesitancy" is an emerging term in the literature and discourse on vaccine decision-making and determinants of vaccine acceptance. It recognizes a continuum between the domains of vaccine acceptance and vaccine refusal and de-polarizes previous characterization of individuals and groups as either anti-vaccine or pro-vaccine. The primary aims of this systematic review are to: 1) identify research on vaccine hesitancy; 2) identify determinants of vaccine hesitancy in different settings including its context-specific causes, its expression and its impact; and 3) inform the development of a model for assessing determinants of vaccine hesitancy in different settings as proposed by the Strategic Advisory Group of Experts Working Group (SAGE WG) for dealing with vaccine hesitancy. A broad search strategy, built to capture multiple dimensions of public trust, confidence and hesitancy around vaccines, was applied across multiple databases. Peer-reviewed studies were selected for inclusion if they focused on childhood vaccines [≤ 7 years of age], used multivariate analyses, and were published between January 2007 and November 2012. Our results show a variety of factors as being associated with vaccine hesitancy but they do not allow for a complete classification and confirmation of their independent and relative strength of influence. Determinants of vaccine hesitancy are complex and context-specific - varying across time, place and vaccines. Copyright © 2014 Elsevier Ltd. All rights reserved.
Kim, Se Mi; Kim, Young-Il; Park, Su-Jin; Kim, Eun-Ha; Kwon, Hyeok-Il; Si, Young-Jae; Lee, In-Won; Song, Min-Suk; Choi, Young Ki
In order to produce a dually effective vaccine against H9 and H5 avian influenza viruses that aligns with the DIVA (differentiating infected from vaccinated animals) strategy, we generated a chimeric H9/H5N2 recombinant vaccine that expressed the whole HA1 region of A/CK/Korea/04163/04 (H9N2) and the HA2 region of recent highly pathogenic avian influenza (HPAI) A/MD/Korea/W452/14 (H5N8) viruses. The chimeric H9/H5N2 virus showed in vitro and in vivo growth properties and virulence that were similar to those of the low-pathogenic avian influenza (LPAI) H9 virus. An inactivated vaccine based on this chimeric virus induced serum neutralizing (SN) antibodies against both H9 and H5 viruses but induced cross-reactive hemagglutination inhibition (HI) antibody only against H9 viruses. Thus, this suggests its compatibility for use in the DIVA strategy against H5 strains. Furthermore, the chimeric H9/H5N2 recombinant vaccine protected immunized chickens against lethal challenge by HPAI H5N8 viruses and significantly attenuated virus shedding after infection by both H9N2 and HPAI H5N8 viruses. In mice, serological analyses confirmed that HA1- and HA2 stalk-specific antibody responses were induced by vaccination and that the DIVA principle could be employed through the use of an HI assay against H5 viruses. Furthermore, each HA1- and HA2 stalk-specific antibody response was sufficient to inhibit viral replication and protect the chimeric virus-immunized mice from lethal challenge with both mouse-adapted H9N2 and wild-type HPAI H5N1 viruses, although differences in vaccine efficacy against a homologous H9 virus (HA1 head domain immune-mediated protection) and a heterosubtypic H5 virus (HA2 stalk domain immune-mediated protection) were observed. Taken together, these results demonstrate that the novel chimeric H9/H5N2 recombinant virus is a low-pathogenic virus, and this chimeric vaccine is suitable for a DIVA vaccine with broad-spectrum neutralizing antibody against H5 avian
Mohapatra, Jajati K; Pandey, Laxmi K; Sanyal, Aniket; Pattnaik, Bramhadev
In India, the proportion of bovines vaccinated against foot-and-mouth disease (FMD) is increasing since the implementation of the Government supported 'FMD Control Programme', and non-structural protein (NSP)-based serological assays for discriminating between antibodies induced by infection or vaccination (DIVA) could be useful. The FMD virus NSP 3AB was expressed in a prokaryotic system and an indirect ELISA (r3AB(3) I-ELISA) was developed and validated as a screening assay for detecting virus in vaccinated bovines. The diagnostic sensitivity of the assay was estimated to be 96%, while the diagnostic specificity varied between the naïve and vaccinates as 99.1% and 96.4%, respectively. This assay could detect antibodies to 3AB (3AB-Ab) from 10 to as late as 900 days post-infection in cattle infected experimentally. The "in-house" assay demonstrated higher sensitivity than a commercial 3ABC ELISA kit particularly with samples obtained from the late stages of infection. Transient post-vaccinal 3AB-Ab response could be detected in one of the three commercial vaccines during the six-month vaccination regimen, which emphasizes the fact that for a DIVA-compatible diagnostic strategy to be a realistic option, all vaccines need to be quality checked for the NSP content. Copyright © 2011 Elsevier B.V. All rights reserved.
Masoud Khalili Sabet
Full Text Available "Attention deficit hyperactivity disorder (ADHD is the most common neurobehavioral disorder of childhood. ADHD is also among the most prevalent chronic health conditions affecting school-aged children"(American Academy of Pediatrics, 2000. Too many young girls are not getting the help they need because of hidden symptoms and late diagnosis. The purpose of this study is to determine the effect of focus strategies on vocabulary learning of ADHD students at two junior high schools. To this end, eight female ADHD and eight normal students from two public schools were assigned to the both control group and the experimental one. The quantitative data was gathered from each student and was analyzed through 2-way analysis of variance (ANOVA in a factorial arrangement with two repetitions. An orthogonal test was used to compare the strategies that were used in the control group (word list and the experimental group (key word method, concentration, making sentences and fold overs. The instrument of this study contained a questionnaire sent to the parents and English teachers, an interview with a psychologist, a pre-test and a post-test. The results indicated that the four focus strategies in the experimental group increased the vocabulary learning in ADHD students for the short term retention and this increase was significant in the first focus strategy (key word method and mostly the last one (fold overs in the normal and ADHD students. The mean scores of control group were lower than the treatment group both in the normal and ADHD students. The results of delayed post-test revealed that although focus strategies improved the scores of the normal students compared to the ADHD students, this difference was not significant.
Full Text Available BACKGROUND: Immigrants have increased mortality from hepatocellular carcinoma as compared to the host populations, primarily due to undetected chronic hepatitis B virus (HBV infection. Despite this, there are no systematic programs in most immigrant-receiving countries to screen for chronic HBV infection and immigrants are not routinely offered HBV vaccination outside of the universal childhood vaccination program. METHODS AND FINDINGS: A cost-effective analysis was performed to compare four HBV screening and vaccination strategies with no intervention in a hypothetical cohort of newly-arriving adult Canadian immigrants. The strategies considered were a universal vaccination, b screening for prior immunity and vaccination, c chronic HBV screening and treatment, and d combined screening for chronic HBV and prior immunity, treatment and vaccination. The analysis was performed from a societal perspective, using a Markov model. Seroprevalence estimates, annual transition probabilities, health-care costs (in Canadian dollars, and utilities were obtained from the published literature. Acute HBV infection, mortality from chronic HBV, quality-adjusted life years (QALYs, and costs were modeled over the lifetime of the cohort of immigrants. Costs and QALYs were discounted at a rate of 3% per year. Screening for chronic HBV infection, and offering treatment if indicated, was found to be the most cost-effective intervention and was estimated to cost $40,880 per additional QALY gained, relative to no intervention. This strategy was most cost-effective for immigrants < 55 years of age and would cost < $50,000 per additional QALY gained for immigrants from areas where HBV seroprevalence is ≥ 3%. Strategies that included HBV vaccination were either prohibitively expensive or dominated by the chronic HBV screening strategy. CONCLUSIONS: Screening for chronic HBV infection from regions where most Canadian immigrants originate, except for Latin America and the
Full Text Available Influenza vaccine immunogenicity is diminished in patients living with HIV/AIDS. We evaluated the cost-effectiveness and expected value of perfect information (EVPI of three alternative influenza vaccine dosing strategies intended to increase immunogenicity in those patients.A randomized, multi-centered, controlled, vaccine trial was conducted at 12 CIHR Canadian HIV Trials Network sites. Three dosing strategies with seasonal, inactivated trivalent, non-adjuvanted intramuscular vaccine were used in HIV infected adults: two standard doses over 28 days (Strategy A, two double doses over 28 days (Strategy B and a single standard dose of influenza vaccine (Strategy C, administered prior to the 2008 influenza season. The comparator in our analysis was practice in the previous year, in which 82.8% of HIV/AIDS received standard-dose vaccination (Strategy D. A Markov cohort model was developed to estimate the monthly probability of Influenza-like Illness (ILI over one influenza season. Costs and quality-adjusted life years, extrapolated to the lifetime of the hypothetical study cohorts, were estimated in calculating incremental cost-effectiveness ratios (ICER and EVPI in conducting further research.298 patients with median CD4 of 470 cells/µl and 76% with viral load suppression were randomized. Strategy C was the most cost-effective strategy for the overall trial population and for suppressed and unsuppressed individuals. Mean ICERs for Strategy A for unsuppressed patients could also be considered cost-effective. The level of uncertainty regarding the decision to implement strategy A versus C for unsuppressed individuals was high. The maximum acceptable cost of reducing decision uncertainty in implementing strategy A for individuals with unsuppressed pVL was $418,000--below the cost of conducting a larger-scale trial.Our results do not support a policy to implement increased antigen dose or booster dosing strategies with seasonal, inactivated trivalent
Wera, Ewaldus; Mourits, Monique C M; Hogeveen, Henk
The cost-effectiveness of different mass dog rabies vaccination strategies, defined as the costs per year of life lost (YLL) averted was evaluated for a period of 10 years by means of a dynamic simulation study for a typical village on Flores Island. In the base strategy (no dog vaccination and no post-exposure treatment (PET) of human bite cases), the model showed that the introduction of the virus by one infectious dog into an isolated village with 1500 inhabitants and 400 dogs resulted in 881 YLLs during a 10-year simulation period, which is equivalent to 30 human rabies cases. An annual dog vaccination campaign with a coverage of 70% using a short-acting vaccine saved 832 YLLs, while the cumulative costs for the public sector were US$3646 or US$4.38 per YLL averted. Switching to a long-acting vaccine, the annual vaccination strategies with a coverage of 50% (AV_156_50) or 70% (AV_156_70) reduced the baseline YLLs from 881 to respectively 78 and 26 YLLs with cumulative costs of US$3716 and US$2264 or US$4.63 and US$2.65 per YLL averted, respectively. In general, dog vaccination was more cost-effective than PET alone (US$2.65-4.63 per YLL averted versus US$23.29 per YLL averted). Although a combination of PET with AV_156_70 was less cost-effective compared to AV_156_70 alone, this strategy was able to prevent all human deaths due to rabies. A combination of PET with annual vaccination using a short-acting vaccine at a coverage of 50% was far from being cost-effective, suggesting that the currently applied rabies control in Flores Island is not an efficient investment in reducing human rabies burden. An increased investment in either an increase in the current coverage or in a switch from the short-acting vaccine to the long-acting vaccine type would certainly pay off. Copyright © 2017 Elsevier Ltd. All rights reserved.
Gao, Haijuan; Okoror, Titilayo A; Hyner, Gerald C
An increasing need for Human Papillomavirus (HPV) vaccines in China remains unmet in the mainland and the knowledge and intentions of Chinese youth regarding vaccination is unknown. In the fall of 2013, 44 Chinese international students (CIS) attending a university in the United States Midwest participated in 10 focus group discussions (five female and five male). Result showed that participants have limited awareness and knowledge about HPV infection and vaccination, participants erroneously believed that the causes of cervical cancer are abortion and miscarriage. Participants rely heavily on informal sources such as Chinese-based social media platforms and personal social networks for information on sexually transmitted infections. Sexual cultures and behaviors are perceived differently between CIS born in the 1990s and 1980s. Interestingly, participants' perceived stigma about HPV infection decreased with improving knowledge level during group discussions. In conclusion, HPV vaccine should be further promoted alongside sex education among CIS.
Melbye, Elisabeth L; Hansen, Håvard
There is a general lack of research addressing the motivations behind parental use of various feeding practices. Therefore, the present work aims to extend the current literature on parent-child feeding interactions by integrating the traditional developmental psychological perspective on feeding practices with elements of Regulatory Focus Theory (RFT) derived from the field of motivational psychology. In this paper, we seek to explain associations between parental feeding practices and child (un)healthy eating behaviors by categorizing parental feeding practices into promotion and prevention focused strategies, thus exploring parent-child feeding interactions within the framework of RFT. Our analyses partly supported the idea that (1) child healthy eating is positively associated with feeding practices characterized as promotion focused, and (2) child unhealthy eating is negatively associated with feeding practices characterized as prevention focused. However, a general observation following from our results suggests that parents' major driving forces behind reducing children's consumption of unhealthy food items and increasing their consumption of healthy food items are strategies that motivate rather than restrict. In particular, parents' provision of a healthy home food environment seems to be essential for child eating.
Elisabeth L. Melbye
Full Text Available There is a general lack of research addressing the motivations behind parental use of various feeding practices. Therefore, the present work aims to extend the current literature on parent-child feeding interactions by integrating the traditional developmental psychological perspective on feeding practices with elements of Regulatory Focus Theory (RFT derived from the field of motivational psychology. In this paper, we seek to explain associations between parental feeding practices and child (unhealthy eating behaviors by categorizing parental feeding practices into promotion and prevention focused strategies, thus exploring parent-child feeding interactions within the framework of RFT. Our analyses partly supported the idea that (1 child healthy eating is positively associated with feeding practices characterized as promotion focused, and (2 child unhealthy eating is negatively associated with feeding practices characterized as prevention focused. However, a general observation following from our results suggests that parents’ major driving forces behind reducing children’s consumption of unhealthy food items and increasing their consumption of healthy food items are strategies that motivate rather than restrict. In particular, parents’ provision of a healthy home food environment seems to be essential for child eating.
Senapati, Rashmirani; Nayak, Bhagyalaxmi; Kar, Shantanu Kumar; Dwibedi, Bhagirathi
HPV is the major causative agent for cervical cancer. Study on the risk of cervical cancer associated with different hr-HPV genotypes would be useful for disease management and new vaccine strategy. With limited reports available, the present study aimed to investigate the pattern of HPV genotypes coinfections and risk of cervical carcinoma associated with them in Indian population. 15 HPV genotypes were detected by E6/E7 multiplex nested type-specific PCR in the HPV-positive cervical samples of 172 cervical cancer cases and 174 subjects with normal cytology. Association between the genotypes and cervical cancer was estimated by calculating the Odds ratio and 95% confidence interval. Risk of cervical carcinoma was associated with multiple genotypes excluding HPV16 (OR:5.87; 95% CI-1.28-26-29; p = .02), multiple genotypes excluding HPV18 (OR = 2.5; 95% CI = 1.09-6.05; p = .03), multiple genotypes of α9 species(OR = 5.3 95% CI = 1.14-24.03; p = .007), and multiple genotypes of α7 species (OR = 2.5; 95% CI = .49-13.45; p = .2). Genotypes not targeted by quadrivalent vaccine types (OR = 2.94 95% CI = 1.48-5.80; p = .001) conferred 2.94 fold higher risk of cervical carcinoma. Cases those coinfected with phylogenetically related genotypes (OR = 2.29; 95% CI(.69-7.59) p = .17) were at 2.9 fold higher risk of invasive cervical carcinoma than those infected with other genotypes although it is not statistically significant. Whereas phylogenetically unrelated genotypes coinfection is negatively associated with cervical carcinoma (OR = .44 95% CI (.244-.8) p = .007) and it is statistically significant.Genotypes not targeted by 9-valent vaccines (OR = .40; 95% CI = .19-.85; p = .017) associated with lesser risk of cervical carcinoma as compared to other genotypes. Subjects infected with any HPV genotype/genotypes excluding HPV16 in association with HPV 18 (OR = 4.1; 95% CI = 1.81-9.25 P = < .001) were at 4.1 fold higher risk of developing invasive cervical carcinoma
Full Text Available Abstract Background During the vaccination campaigns, puppies younger than 3 months old are not targeted and remain unvaccinated for at least the first year of their lives. Almost half of the reported rabid dogs are 6 months or younger. Hence, we should recommend the vaccination against rabies of young puppies. Unfortunately, owing to the exposure of puppies to infections with either canine parvovirus (CPV or distemper virus (CDV after the intervention of the vaccinators, owners are reluctant to vaccinate puppies against rabies. Therefore, it is necessary to include the CPV and CDV valences in the vaccine against rabies. Multivalent DNA-based vaccination in dogs, including rabies and distemper valences, could help in raising vaccine coverage. Methods We have designed monovalent and multivalent DNA-based vaccine candidates for in vitro and in vivo assays. These plasmids encode to the rabies virus glycoprotein and/or the canine distemper virus hemagglutinin. The first strategy of multivalent DNA-based vaccination is by mixing plasmids encoding to a single antigen each. The second is by simply fusing the genes of the antigens together. The third is by adding the foot and mouth disease virus (FMDV 2A oligopeptide gene into the antigen genes. The last strategy is by the design and use of a bicistronic plasmid with an “Internal Ribosome Entry Site” (IRES domain. Results The monovalent construct against canine distemper was efficiently validated by inducing higher humoral immune responses compared to cell-culture-derived vaccine both in mice and dogs. All multivalent plasmids efficiently expressed both valences after in vitro transfection of BHK-21 cells. In BALB/c mice, the bicistronic IRES-dependant construct was the most efficient inducer of virus-neutralizing antibodies against both valences. It was able to induce better humoral immune responses compared to the administration of either cell-culture-derived vaccines or monovalent plasmids. The
Howlett, Roberta I; Miller, Anthony B; Pasut, George; Mai, Verna
The purpose of this paper is to outline the short-, medium- and long-term requirements of a strategy to evaluate the impact of HPV immunization and to define a framework to facilitate planning and evaluation. This strategy was developed in Ontario from January to August 2008. Literature review was completed to assess existing material relevant to vaccine evaluation, and HPV vaccine specifically. Scientists and epidemiologists within our organization attended meetings to brainstorm and identify key requirements for vaccine evaluation. Other selected internal and external experts were consulted to review preliminary lists of potential indicators and questions for inclusion in an evaluation strategy. Results are reported in three sections--literature review, proposed evaluation framework and data requirements. The first vaccine evaluation strategy that integrates primary and secondary prevention of cervical cancer is presented. Among women who are neither screened nor immunized, customized interventions will be required to ensure that they are aware of potential risks and benefits. This evaluation strategy may serve as a useful outline for jurisdictions in Canada and elsewhere. This new paradigm of combined primary and secondary intervention will encourage cooperation for effective evaluation of an integrated approach for control of cervical cancer and other HPV-related disease.
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.
Cho, Hyun-Il; Jung, Soo-Hyun; Sohn, Hyun-Jung; Celis, Esteban; Kim, Tai-Gyu
Therapeutic cancer vaccines are an attractive alternative to conventional therapies for treating malignant tumors, and successful tumor eradication depends primarily on obtaining high numbers of long-lasting tumor-reactive CD8+ T cells. Dendritic cell (DC)-based vaccines constitute a promising approach for treating cancer, but in most instances low immune responses and suboptimal therapeutic effects are achieved indicating that further optimization is required. We describe here a novel vaccination strategy with peptide-loaded DCs followed by a mixture of synthetic peptides, polyinosine-polycytidylic acid (poly-IC) and anti-CD40 antibodies (TriVax) for improving the immunogenicity and therapeutic efficacy of DC-based vaccines in a melanoma mouse model. TriVax immunization 7-12 d after priming with antigen-loaded DCs generated large numbers of long-lasting multiple antigen-specific CD8+ T cells capable of recognizing tumor cells. These responses were far superior to those generated by homologous immunizations with either TriVax or DCs. CD8+ T cells but not CD4+ T cells or NK cells mediated the therapeutic efficacy of this heterologous prime-boost strategy. Moreover, combinations of this vaccination regimen with programmed cell death-1 (PD-1) blockade or IL2 anti-IL2 antibody complexes led to complete disease eradication and survival enhancement in melanoma-bearing mice. The overall results suggest that similar strategies would be applicable for the design of effective therapeutic vaccination for treating viral diseases and various cancers, which may circumvent current limitations of cell-based cancer vaccines.
Cho, Hyun-Il; Jung, Soo-Hyun; Sohn, Hyun-Jung; Celis, Esteban; Kim, Tai-Gyu
Therapeutic cancer vaccines are an attractive alternative to conventional therapies for treating malignant tumors, and successful tumor eradication depends primarily on obtaining high numbers of long-lasting tumor-reactive CD8+ T cells. Dendritic cell (DC)-based vaccines constitute a promising approach for treating cancer, but in most instances low immune responses and suboptimal therapeutic effects are achieved indicating that further optimization is required. We describe here a novel vaccination strategy with peptide-loaded DCs followed by a mixture of synthetic peptides, polyinosine-polycytidylic acid (poly-IC) and anti-CD40 antibodies (TriVax) for improving the immunogenicity and therapeutic efficacy of DC-based vaccines in a melanoma mouse model. TriVax immunization 7–12 d after priming with antigen-loaded DCs generated large numbers of long-lasting multiple antigen-specific CD8+ T cells capable of recognizing tumor cells. These responses were far superior to those generated by homologous immunizations with either TriVax or DCs. CD8+ T cells but not CD4+ T cells or NK cells mediated the therapeutic efficacy of this heterologous prime-boost strategy. Moreover, combinations of this vaccination regimen with programmed cell death-1 (PD-1) blockade or IL2 anti-IL2 antibody complexes led to complete disease eradication and survival enhancement in melanoma-bearing mice. The overall results suggest that similar strategies would be applicable for the design of effective therapeutic vaccination for treating viral diseases and various cancers, which may circumvent current limitations of cell-based cancer vaccines. PMID:26451316
Garcia Clavero, Ana Belén; Madsen, A.; Vigre, Håkan
’ exposure to Campylobacter.In this presentation we focus on the development of a computerized decision support system to aid management decisions on Campylobacter vaccination of commercial broilers. Broilers should be vaccinated against Campylobacter in the first 2 weeks of age. Therefore, the decision......Human campylobacteriosis represents an important economic and public health problem. Campylobacter originating from feces of infected chickens will contaminate chicken meat posing a risk to the consumer. Vaccination against Campylobacter in broilers is one probable measure to reduce consumers...... about vaccination needs to be made usually before Campylobacter is introduced in the flock. In fact, there is uncertainty regarding the introduction of Campylobacter into the flock that needs to be taken into account in the decision making process. Probabilistic Graphical Models (PGMs) integrate...
Fitria, Irma; Winarni, Pancahayani, Sigit; Subchan
This paper discussed regarding a model and an optimal control problem of dengue fever transmission. We classified the model as human and vector (mosquito) population classes. For the human population, there are three subclasses, such as susceptible, infected, and resistant classes. Then, for the vector population, we divided it into wiggler, susceptible, and infected vector classes. Thus, the model consists of six dynamic equations. To minimize the number of dengue fever cases, we designed two optimal control variables in the model, the giving of fogging and vaccination. The objective function of this optimal control problem is to minimize the number of infected human population, the number of vector, and the cost of the controlling efforts. By giving the fogging optimally, the number of vector can be minimized. In this case, we considered the giving of vaccination as a control variable because it is one of the efforts that are being developed to reduce the spreading of dengue fever. We used Pontryagin Minimum Principle to solve the optimal control problem. Furthermore, the numerical simulation results are given to show the effect of the optimal control strategies in order to minimize the epidemic of dengue fever.
Holdsworth, Mark T; Benson, Blaine E; Dole, Ernest J
To highlight the limitations of community pharmacy practice and to propose a system change by implementing a risk-assessment method and management strategy for opioids in this arena. Selected by the author. Numerous studies show that the U.S. health care system is subject to a high rate of drug misadventures involving primarily low therapeutic index drugs, especially opioids. Currently proposed approaches to managing opioids focus on access control, but without a broader consideration of patient-use problems that lead to morbidity and mortality. While pharmacists are well-trained health professionals, their primary focus has been on drug distribution rather than proper use. This article highlights the limitations in contemporary community pharmacy practice that likely contribute to the problem of opioid misuse and resultant morbidity. A new model of practice is proposed whereby the most dangerous agents such as opioids are preidentified for a more formalized risk-based strategy focused upon optimal patient education and required follow-up.
Full Text Available The ability to devote attention simultaneously to multiple visual objects plays an important role in domains ranging from everyday activities to the workplace. Yet, no studies have systematically explored the fixation strategies that optimize attention to two spatially distinct objects. Assuming the two objects require attention nearly simultaneously, subjects either could fixate one object or they could fixate between the objects. Studies measuring the breadth of attention have focused almost exclusively on the former strategy, by having subjects simultaneously perform one attention-demanding task at fixation and another in the periphery. We compared performance when one object was at fixation and the other was in the periphery to a condition in which both objects were in the periphery and subjects fixated between them. Performance was better with two peripheral stimuli than with one central and one peripheral stimulus, meaning that a strategy of fixating between stimuli permitted greater attention breadth. Consistent with the idea that both measures tap attention breadth, sport experts consistently outperformed novices with both fixation strategies. Our findings suggest a way to improve performance when observers must pay attention to multiple objects across spatial regions. We discuss possible explanations for this performance advantage.
Innes, Elisabeth A; Bartley, Paul M; Maley, Stephen W; Wright, Stephen E; Buxton, David
Toxoplasma gondii and Neospora caninum are important causes of reproductive loss in ruminant species worldwide. Both parasites cause disease during pregnancy that may result in foetal death or birth of live congenitally infected offspring. T. gondii is also an important human pathogen with the main risk groups including pregnant women and immuno-compromised individuals, although clinical disease has also been observed in outbreaks among immuno-competent people. While the two parasites are closely related there are distinct differences between the two in their interactions with different host species and subsequent clinical outcome. This paper discusses the respective host-parasite relationships in ovine toxoplasmosis and bovine neosporosis and how the immune response may be host-protective, parasite-protective or contribute to disease pathogenesis, and how this knowledge may help in the development of more effective and targeted vaccination strategies.
New vaccine strategies against enterotoxigenic Escherichia coli: II: Enhanced systemic and secreted antibody responses against the CFA/I fimbriae by priming with DNA and boosting with a live recombinant Salmonella vaccine
Full Text Available The induction of systemic (IgG and mucosal (IgA antibody responses against the colonization factor I antigen (CFA/I of enterotoxigenic Escherichia coli (ETEC was evaluated in mice primed with an intramuscularly delivered CFA/I-encoding DNA vaccine followed by two oral immunizations with a live recombinant Salmonella typhimurium vaccine strain expressing the ETEC antigen. The booster effect induced by the oral immunization was detected two weeks and one year after the administration of the DNA vaccine. The DNA-primed/Salmonella-boosted vaccination regime showed a synergistic effect on the induced CFA/I-specific systemic and secreted antibody levels which could not be attained by either immunization strategy alone. These results suggest that the combined use of DNA vaccines and recombinant Salmonella vaccine strains can be a useful immunization strategy against enteric pathogens.
Kim, Son C; Brown, Caroline E; Fields, Willa; Stichler, Jaynelle F
This paper is a report of a study to evaluate the effectiveness of the evidence-based practice (EBP)-focused interactive teaching (E-FIT) strategy. Although EBP is a mandatory competency for all healthcare professionals, little is known about the effectiveness of E-FIT in nursing. Aquasi-experimental, controlled, pre- and post-test study involving senior, 4th-year nursing students (N = 208) at two nursing schools in the USA was carried out from August 2007 to May 2008. The experimental group (n = 88) received the E-FIT strategy intervention and the control group (n = 120) received standard teaching. A Knowledge, Attitudes and Behaviors Questionnaire for Evidence-Based Practice was used to assess the effectiveness of the E-FIT strategy. Independent t-tests showed that the experimental group had statistically significant higher post-test Evidence-Based Practice Knowledge (mean difference = 0.25; P = 0.001) and Evidence-Based Practice Use (mean difference = 0.26; P = 0.015) subscale scores compared to the control group, but showed no statistically significant differences in Attitudes toward Evidence-Based Practice and Future Use of Evidence-Based Practice (mean difference = 0.12; P = 0.398 and mean difference = 0.13; P = 0.255 respectively). Hierarchical multiple regression analyses of the post-test data indicated that the intervention explained 7.6% and 5.1% of variance in Evidence-Based Practice Knowledge and Evidence-Based Practice Use respectively. The EBP-focused interactive teaching strategy was effective in improving the knowledge and use of EBP among nursing students but not attitudes toward or future use of EBP.
Strandmark K, Margaretha; Rahm, GullBritt; Wilde Larsson, Bodil; Nordström, Gun; Rystedt, Ingrid
The aim of the present study was to explore preventive strategies and processes to counteract bullying in workplaces. Data were collected by individual interviews and focus group discussions at one hospital and two nursing home wards for elderly, a total of 29 participants. In the analysis of the interviews we were inspired by constructivist grounded theory. Persistent work with a humanistic value system by supervisor and coworkers, raising awareness about the bullying problem, strong group collaboration, and conflict management, along with an open atmosphere at the workplace, appears to be imperative for accomplishing a policy of zero tolerance for bullying.
. Immunization with the corresponding synthetic peptides was followed by a decrease of 70% of parasite fecundity and egg viability. As a preliminary step towards phase I human trials, vaccination experiments have been performed in cattle, a natural model for Schistosoma bovis. Vaccination of calves with the S. bovis GST has led to a reduction of ever 80% of egg output and tissue egg count. Significant levels of protection were also observed in goats after immunization with the recombinant S. bovis GST. Increasing evidence of the participation of IgA antibodies in protective immunity has prompted us toward the development of mucosal immunization. Preliminary results indicate that significant levels of protection can be achieved following oral immunization with live attenuated vectors or liposomes. These studies seem to represent a promising approach towards the future development of a vaccine strategy against one of major human parasitic diseases.
This study investigates the effects of framing and risk perception, and their interaction effects on human papillomavirus (HPV) vaccination. Based on a 2 (message frames) × 2 (perceived risk) experimental design, the interaction effects reveal the effectiveness of loss- (vs. gain-) framed messages would be maximized for high (vs. low) perceived risk condition. Based on regulatory fit principles the synergy effects are shown in terms of attitudes toward advertising and HPV vaccination, HPV vaccination intention, and ad-promoted behavioral intention. The findings indicate right message appeals should be selected for the right target audiences in the setting of HPV vaccine promotions.
Postma, Maarten J.; de Vries, Robin; Roord, John
This letter reacts on a paper recently published in this journal, reviewing the effectiveness and (cost-)effectiveness of pertussis booster vaccination strategies. We argue that a different selection of (cost-)effectiveness data could validly be made than the one presented in the review as being
Dempsey, Amanda F; Espinosa, Claudia; Davis, Matthew M
Among a hypothetical cohort of 11-18-year-old females, we used a probabilistic decision tree model to estimate the number of pregnant adolescent females potentially receiving contraindicated vaccines during well child exams, and to determine the impact of two different pregnancy screening strategies on pregnancy detection rates, vaccine administration and pregnancy detection-associated costs. We found that under current practice conditions, the majority (95-99%) of adolescent pregnancies are likely missed during well child exams, allowing the opportunity to administer contraindicated vaccines. A strategy to test everyone detected the highest proportion of pregnancies, but at a substantial financial cost (USD 12,270,037-USD 19,430,607). Testing was more efficient for older adolescents, but both testing strategies were associated with a significant number of false positive test results (41-98%), regardless of age. These results suggest that systematic pregnancy screening strategies would be effective for preventing pregnant adolescents from receiving contraindicated vaccines, but may not be worth the potentially high financial and psychological costs.
Dai, Yang; Wang, Xiaoting; Tang, Jianxia; Zhao, Song; Xing, Yuntian; Dai, Jianrong; Jin, Xiaolin; Zhu, Yinchang
Schistosomiasis japonica is a zoonotic parasitic disease; developing transmission blocking veterinary vaccines are urgently needed for the prevention and control of schistosomiasis in China. Heterologous prime-boost strategy, a novel vaccination approach, is more effective in enhancing vaccine efficacy against multiple pathogens. In the present study, we established a novel heterologous prime-boost vaccination strategy, the rAdV-SjTPI.opt intramuscular priming and rSjTPI subcutaneous boosting strategy, and evaluated its protective efficacy against Schistosoma japonicum in mice. Adenoviral vectored vaccine (rAdV-SjTPI.opt) and recombinant protein vaccine (rSjTPI) were prepared and used in different combinations as vaccines in a mouse model. The specific immune responses and protective efficacies were evaluated. Furthermore, the longevity of protective efficacy was also determined. Results showed that the rAdV-SjTPI.opt priming-rSjTPI boosting strategy elicited higher levels of specific IgG responses and broad-spectrum specific cellular immune responses. The protective efficacy could reach up to nearly 70% and 50% of protection could be observed at 10 weeks after the last immunization in mice. The rAdV-SjTPI.opt intramuscular priming-rSjTPI subcutaneous boosting vaccination strategy is a novel, highly efficient, and stable approach to developing vaccines against Schistosoma japonicum infections in China.
Full Text Available Schistosomiasis japonica is a zoonotic parasitic disease; developing transmission blocking veterinary vaccines are urgently needed for the prevention and control of schistosomiasis in China. Heterologous prime-boost strategy, a novel vaccination approach, is more effective in enhancing vaccine efficacy against multiple pathogens. In the present study, we established a novel heterologous prime-boost vaccination strategy, the rAdV-SjTPI.opt intramuscular priming and rSjTPI subcutaneous boosting strategy, and evaluated its protective efficacy against Schistosoma japonicum in mice.Adenoviral vectored vaccine (rAdV-SjTPI.opt and recombinant protein vaccine (rSjTPI were prepared and used in different combinations as vaccines in a mouse model. The specific immune responses and protective efficacies were evaluated. Furthermore, the longevity of protective efficacy was also determined. Results showed that the rAdV-SjTPI.opt priming-rSjTPI boosting strategy elicited higher levels of specific IgG responses and broad-spectrum specific cellular immune responses. The protective efficacy could reach up to nearly 70% and 50% of protection could be observed at 10 weeks after the last immunization in mice.The rAdV-SjTPI.opt intramuscular priming-rSjTPI subcutaneous boosting vaccination strategy is a novel, highly efficient, and stable approach to developing vaccines against Schistosoma japonicum infections in China.
Full Text Available Background and Objectives: Postpartum depression is one of most important health problems in women. This study was performed with the purpose of comparing the frequency of postpartum depression in pregnant women with emotion and problem-focused coping strategies. Methods: This study was conducted as a prospective cohort study on 200 pregnant women with stress (low and high levels. The samples were pregnant women referred to all health-treatment, centers of Ardabil, which were selected using a multi-stage sampling method; and according to coping strategy, they were divided into two groups: emotion-focused and problem-focused. Low-risk pregnant women completed questionnaires about demographic characteristics, perceived stress, and Billings and Moos coping strategies in the 38th to 42th week of their pregnancy, and completed the Edinburgh depression scale in the 3th to 4th weeks after childbirth. Data were analyzed using chi 2 and t tests. p<0.05 considered significant.Results: In this study, 170 participant women (85% used emotion-focused strategy and 30 women (15% used problem-focused strategy. Frequency of postpartum depression was 6.7% in the problem-focused group and 8.2% in the emotion-focused group. There was no significant difference in the frequency of postpartum depression between women with the problem- and emotion-focused strategies. Relative risk for postpartum depression was 1.2 times more among the women used emotion-focused strategy than women used problem-focused strategy (p<0.05.Conclusion: According to the results of this study, there was no significant relationship between postpartum depression and the two emotion-focused and problem-focused coping strategies. This can be due to high influence of postpartum specific endocrine factors in the etiology of this type of depression compared to other depressions.
Full Text Available In recent years, heterologous prime-boost vaccines have been demonstrated to be an effective strategy for generating protective immunity, consisting of both humoral and cell-mediated immune responses against a variety of pathogens including HIV-1. Previous reports of preclinical and clinical studies have shown the enhanced immunogenicity of viral vector or DNA vaccination followed by heterologous protein boost, compared to using either prime or boost components alone. With such approaches, the selection of an adjuvant for inclusion in the protein boost component is expected to impact the immunogenicity and safety of a vaccine. In this study, we examined in a mouse model the serum cytokine and chemokine profiles for several candidate adjuvants: QS-21, Al(OH3, monophosphoryl lipid A (MPLA and ISCOMATRIX™ adjuvant, in the context of a previously tested pentavalent HIV-1 Env DNA prime-protein boost formulation, DP6-001. Our data revealed that the candidate adjuvants in the context of the DP6-001 formulation are characterized by unique serum cytokine and chemokine profiles. Such information will provide valuable guidance in the selection of an adjuvant for future AIDS vaccine development, with the ultimate goal of enhancing immunogenicity while minimizing reactogenicity associated with the use of an adjuvant. More significantly, results reported here will add to the knowledge on how to include an adjuvant in the context of a heterologous prime-protein boost vaccination strategy in general.
Gil Cuesta, Julita; Aavitsland, Preben; Englund, Hélène
During the 2009/10 influenza A(H1N1)pdm09 pandemic, the five Nordic countries adopted different approaches to pandemic vaccination. We compared pandemic vaccination strategies and severe influenza outcomes, in seasons 2009/10 and 2010/11 in these countries with similar influenza surveillance...... and experienced less A(H1N1)pdm09-related severe outcomes in 2010/11. Pandemic vaccination may have had an impact on severe influenza outcomes in the post-pandemic season. Surveillance of severe outcomes may be used to compare the impact of influenza between seasons and support different vaccination strategies....
Smalley, Hannah K; Keskinocak, Pinar; Swann, Julie; Hinman, Alan
In addition to improved sanitation, hygiene, and better access to safe water, oral cholera vaccines can help to control the spread of cholera in the short term. However, there is currently no systematic method for determining the best allocation of oral cholera vaccines to minimize disease incidence in a population where the disease is endemic and resources are limited. We present a mathematical model for optimally allocating vaccines in a region under varying levels of demographic and incidence data availability. The model addresses the questions of where, when, and how many doses of vaccines to send. Considering vaccine efficacies (which may vary based on age and the number of years since vaccination), we analyze distribution strategies which allocate vaccines over multiple years. Results indicate that, given appropriate surveillance data, targeting age groups and regions with the highest disease incidence should be the first priority, followed by other groups primarily in order of disease incidence, as this approach is the most life-saving and cost-effective. A lack of detailed incidence data results in distribution strategies which are not cost-effective and can lead to thousands more deaths from the disease. The mathematical model allows for what-if analysis for various vaccine distribution strategies by providing the ability to easily vary parameters such as numbers and sizes of regions and age groups, risk levels, vaccine price, vaccine efficacy, production capacity and budget. Copyright © 2015 Elsevier Ltd. All rights reserved.
Feenstra, Femke; van Rijn, Piet A
Bluetongue virus (BTV) causes the hemorrhagic disease bluetongue (BT) in ruminants. The best way to control outbreaks is vaccination. Currently, conventionally modified-live and inactivated vaccines are commercially available, which have been successfully used to control BT, but nonetheless have their specific shortcomings. Therefore, there is a need for improved BT vaccines. The ideal BT vaccine is efficacious, safe, affordable, protective against multiple serotypes and enables the differentiation of infected from vaccinated animals. Different field situations require specific vaccine profiles. Single serotype outbreaks in former BT-free areas need rapid onset of protection against viremia of the respective serotype. In contrary, endemic multiple serotype situations require long-lasting protection against all circulating serotypes. The ideal BT vaccine for all field situations does not exist and balancing between vaccine properties is needed. Many new vaccines candidates, ranging from non-replicating subunits to replicating next-generation reverse genetics based vaccines, have been developed. Some have been tested extensively in large numbers of ruminants, whereas others were developed recently and have only been tested in vitro and in mice models. Most vaccine candidates are promising, but have their specific shortcomings and advantages. In this review, current and next-generation BT vaccines are discussed in the light of prerequisites for different field situations.
Full Text Available This study aimed at investigating the effect of dictogloss on EFL learners’ listening comprehension as well as on their use of metacognitive listening strategies with a focus on the effects on male and female learners. To this end, a total number of 50 female and male Iranian EFL learners, aged between 12 and 15 years old, at the intermediate proficiency level in a private language school in Iran were selected and randomly assigned to experimental and control groups with 25 male and female learners in each group. Dictogloss was employed to teach the learners in the experimental group for an instruction period of 12 sessions. Participants’ listening comprehension was determined through a pre/posttest which was adapted from the listening section of the standard test of PET and their use of metacognitive listening strategies via the MALQ, a questionnaire developed by Vandergrift et al. (2006. The data obtained were submitted to the t-test and results revealed significant improvement in the experimental group’s listening comprehension with no significant difference between male and female learners. Finally, the results showed that the listeners in the experimental group made noticeable gains in their choice of metacognitive strategies through using the dictogloss technique. Findings are discussed in light of recent theories of language learning and teaching.
IS IT NECESSARY TO VACCINATE CHILDREN AGAINST HEPATITIS A ROUTINELY IN PRESENT TIME? THE EVALUATION OF RESULTS OF SUCH STRATEGY OF HEPATITIS A VACCINE PROPHYLAXIS IN SELECTED REGIONS OF THE RUSSIAN FEDERATION
I. V. Shakhgildian
Full Text Available Abstract. Data about efficacy of conducting of routine vaccination of children against Hepatitis A are presented in the article. The results of realization such strategy of vaccine prevention of Hepatitis A in selected regions of Russian Federation are evaluated. The perspectives of using this experience in other regions of the country is discussed.
Suwantika, A.A.; Setiawan, D.; Atthobari, J.; Postma, M.J.
Objectives: Rotavirus infection was reported as the major cause of severe diarrhea in children under 5-years-old in Indonesia. A low cost rotavirus vaccine to protect infants from birth has been developed for developing countries, such as Indonesia. This study aims to update our initial analysis on
Boklund, A; Halasa, T; Christiansen, L E; Enøe, C
Recent outbreaks of foot-and-mouth disease (FMD) in Europe have highlighted the need for assessment of control strategies to optimise control of the spread of FMD. Our objectives were to assess the epidemiological and financial impact of simulated FMD outbreaks in Denmark and the effect of using ring depopulation or emergency vaccination to control these outbreaks. Two stochastic simulation models (InterSpreadPlus (ISP) and the modified Davis Animal Disease Simulation model (DTU-DADS)) were used to simulate the spread of FMD in Denmark using different control strategies. Each epidemic was initiated in one herd (index herd), and a total of 5000 index herds were used. Four types of control measures were investigated: (1) a basic scenario including depopulation of detected herds, 3 km protection and 10 km surveillance zones, movement tracing and a three-day national standstill, (2) the basic scenario plus depopulation in ring zones around detected herds (Depop), (3) the basic scenario plus protective vaccination within ring zones around detected herds, and (4) the basic scenario plus protective vaccination within ring zones around detected herds. Disease spread was simulated through direct animal movements, medium-risk contacts (veterinarians, artificial inseminators or milk controllers), low-risk contacts (animal feed and rendering trucks, technicians or visitors), market contacts, abattoir trucks, milk tanks, or local spread. The two simulation models showed different results in terms of the estimated numbers. However, the tendencies in terms of recommendations of strategies were similar for both models. Comparison of the different control strategies showed that, from an epidemiological point of view, protective vaccination would be preferable if the epidemic started in a cattle herd in an area with a high density of cattle, whereas if the epidemic started in an area with a low density of cattle or in other species, protective vaccination or depopulation would have
O. A. Shamsutdinova
Full Text Available The review focuses on the history of the production of live antiviral vaccines and their use for the prevention of infectious diseases. It was noted that before the beginning of the 20th century, only three live vaccines were developed and put into practice — against smallpox, rabies, plague. The discovery of D. Enders, T.H. Weller and F.Ch. Robins of the ability of the polio virus, and then of a number of other viruses, to reproduce in vitro in cell cultures of various types, greatly expanded the studies on the production of attenuated strains of viruses for live vaccines. The historical stages of obtaining and introducing live vaccines for the prevention of smallpox, poliomyelitis, measles, rubella, and mumps are highlighted. Arguments in favor of the use of associated vaccine preparations for the prevention of viral infections are presented. Various variants of the strategy and tactics of using live vaccines, which are used for specific prevention of viral infections in different countries, are described. The review provides information on technological methods for obtaining antiviral vaccines. The publications testifying to the development of specific reactions in immunized vaccine strains of measles, mumps, poliomyelitis and rubella viruses, such as aseptic meningitis (vaccine strains of mumps virus, acute arthritis (vaccine rubella virus strains, temperature reactions, rash (vaccine strains of the virus Measles, vaccine-associated paralytic poliomyelitis (VAPP vaccine vaccine poliovirus. It is particularly noted that the long experience of vaccine prevention both in Russia and abroad convincingly shows that the risk of developing post-vaccination complications is incommensurably lower than the risk of causing harm to health from the corresponding infections. It is concluded that despite introduction of new third and fourth generation vaccines into practice, live attenuated vaccines do not lose their significance and are used in vaccine
He, H Q; Li, Q; Yan, R; Zhou, Y; Tang, X W; Deng, X; Xie, S Y; Chen, Z P
Objective: To assess the 3-year antibody persistence after vaccination of domestic measles, mumps and rubella combined attenuated live vaccine (MMR) with different program. Methods: Children from three different vaccination strategies (Group 8 m MR: 8 months and 18 months vaccinated with measles-rubella combined attenuated live vaccine and domestic MMR,respectively; Group 8 m MMR: 8 months and 18 months both vaccinated with domestic MMR; Group 12 m MMR: 12 months and 22 months both vaccinated with domestic MMR ) were followed up in Zhejiang province in July 2015. There were 170 participants in Group 8 m MR, 171 participants in Group 8 m MMR and 173 participants in Group 12 m MMR selected by simple random sampling method .Blood samples (venous blood 2-3 ml) were collected 1 month after the first dose vaccination of MMR (only in Group 8 m MMR and Group 12 m MMR) and 3 years (36-38 months) after the last dose vaccination of MMR and tested for antibody IgG against Measles, Mumps and Rubella using ELISA. Seropostive rate and Geometric mean concentration (GMC) were calculated and compared among different groups by Chi-square test or Fisher exact test and Kruskal-Wallis H test. Results: A total of 514 participants (8 m MR: 170; 8 m MMR:171; 12 m MMR:173) were enrolled. The overall seropositivity rate of measles, mumps and rubella was 98.1% (504), 93.4% (480) and 88.1% (453), respectively, with corresponding GMC was 1 012.33 mU/ml, 502.87 U/ml and 50.53 U/ml respectively. There was no significant difference of seropositivity rate for measles among three groups (all groups were>97%). The highest seropositivity rate for mumps was found in the Group 12 m MMR with the rate of 98.8% (171/173), followed by Group 8 m MMR and Group 8 m MR with 93.0% (159/171) and 88.2%(150/170) respectively (Fisher exact test, Prubella was also found in the Group 12 m MMR with the rate of 94.8% (164/173), followed by Group 8 m MMR and Group 8 m MR with 86.6%(148/171) and 82
Vaccination is the best way to control myxomatosis in both pet and production rabbits. Two types of myxomatosis vaccines are commercially available, namely, a vaccine prepared from the Shope fibroma virus (SFV) and one prepared from an attenuated myxoma virus (MV) strain, e.g., SG33. The first one is weakly immunogenic and provides only short-term protection whereas atypical reactions have been described with the second one. This short review describes the vaccine strains and provides some data on the host-virus relationship, resistance, and immunity in myxomatosis. In the last section, recommended myxomatosis vaccination schemes for production and pet animals are presented.
Beeke, Suzanne; Beckley, Firle; Johnson, Fiona; Heilemann, Claudia; Edwards, Susan; Maxim, Jane; Best, Wendy
Background: A recent review of interaction (or conversation)-focused therapy highlighted the potential of programmes targeting the person with aphasia (PWA) directly. However, it noted the key limitations of current work in this field to be a reliance on single case analyses and qualitative evidence of change, a situation that is not unusual when a complex behavioural intervention is in the early stages of development and evaluation. Aims: This article aims to evaluate an intervention that targeted a PWA and their conversation partner (CP), a dyad, as equals in a novel conversation therapy for agrammatic aphasia, using both quantitative and qualitative evidence of change. The intervention aimed to increase the insight of a dyad into facilitator and barrier conversation behaviours, to increase the understanding of the effect of agrammatism on communication, and to support each speaker to choose three strategies to work on in therapy to increase mutual understanding and enhance conversation. Methods & Procedures: Quantitative and qualitative methods are used to analyse multiple pre-therapy and follow up assessments of conversation for two dyads. Outcomes & Results: Results show that one person with severe and chronic agrammatic aphasia was able to select and practise strategies that led to qualitative and quantitative changes in his post-therapy conversations. The other PWA showed a numerical increase in one of his three strategies post therapy, but no significant quantitative change. Although both CPs significantly reduced barrier behaviours in their post-therapy conversations, neither showed a significant increase in the strategies they chose to work on. For one CP, there was qualitative evidence of the use of different turn types. Conclusions: Individually tailored input from a speech and language therapist can assist some people with chronic agrammatism to develop conversational strategies that enhance communication. Outcomes are influenced by the severity and
Schmidt, Signe Tandrup; Foged, Camilla; Korsholm, Karen Smith
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...... 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...
Little, Brent A; Meehan, Julianne; Shea, Kimberly M; Pelton, Stephen I
Abstract Background Detecting Streptococcus pneumoniae (SP) carriage in children via conventional microbiological methods lacks sensitivity as high density is required for routine culture and identification of dual serotype colonization is a technical challenge. To increase understanding of post vaccine nasopharyngeal (NP) carriage, specifically persistence of vaccine serotypes, strategies for molecular identification of SP have been developed. These methods most often rely on the identification of the SP autolysin gene lytA through non-quantitative PCR or semi-quantitative real-time PCR (RTPCR). Methods We collected NP swabs from 600 healthy or sick children Pelton, Pfizer: Board Member and Grant Investigator, Consulting fee, Research grant and Speaker honorarium; Merck vaccines: Board Member, Consulting fee and Speaker honorarium; GSK: Board Member, Consulting fee and Speaker honorarium; Sequiris: Board Member, Consulting fee and Speaker honorarium
Johnson, Sharon D; Williams, Sha-Lai
The high rates of sexual risk behaviors, particularly among African American youths who may not be aware of their HIV status, provide indication that, unless prevention efforts are enhanced, this vulnerable group of youths will remain at greater risk for negative health status outcomes. Parents are important in efforts to reduce risk among youths and often have a willingness to be sexuality educators for their children; however, communication barriers often impede their ability to provide preventive sexual health knowledge to their youths. Social workers are often presented with opportunities to help parents develop effective sexual health communication skills in informal settings when formal interventions are not feasible. The present effort considers solution-focused strategies social workers can use to help parents overcome barriers and communicate more positively with their youths about sexual health.
Sen, Surajit; Shanahan, Linda
Detailed and aggregate analyses of the outcome of past battles focusing on rates of troop losses or on the ratios of forces on each side is at the heart of present knowledge about battles. Here we present non-equilibrium statistical mechanics based studies of possible outcomes of well matched strategic battles by a ``blue'' army against insurgency based attacks by well matched opponents in a ``red'' army in red territory. We assume that the red army attacks with randomly varying force levels to potentially confuse and drive the blue's strategies. The temporal evolution of the model battles incorporate randomness in the deployment of the reds and hence possess attendant history dependence. Our results reveal that while unpredictable events play a major role in battles, a balance between risk of exposure in a battlefield and the use of short range intelligence is needed in determining whether one side can decimate the other, and hence force a battle to end.
Full Text Available Abstract Background The prevalence of pleurisies recorded at slaughter is increasing in Sweden, and acute outbreaks of actinobacillosis that require antimicrobial treatments have become more frequent. As an increased use of antimicrobials may result in the development of antimicrobial resistance it is essential to develop alternative measures to control the disease. Vaccinations present an appealing alternative to antimicrobial treatments. The aim of this work was to evaluate the potential of two different vaccination strategies in a specialized fattening herd affected by actinobacillosis. Methods The study was conducted in a specialized fattening herd employing age segregated rearing in eight units. The herd suffered from infections caused by Actinobacillus pleuropneumoniae serotype 2, confirmed by necropsy and serology. The study included 54 batches of pigs grouped into five periods. Batches of pigs of the second period were vaccinated against actinobacillosis twice, and pigs in the fourth period were vaccinated three times. Batches of pigs of the first, third and fifth period were not vaccinated. Concentrations of serum antibodies to A. pleuropneumoniae and serum amyloid A (SAA were analysed and production data were recorded. Results Despite vaccinating, medical treatments were required to reduce the impact of the disease. The mean incidence of individual treatments for respiratory diseases during the rearing period ranged from 0 to 4.7 ± 1.8%, and was greatest during the triple vaccination period (period IV; p A. pleuropneumoniae serotype 2 in the absence of a SAA-response. The prevalence of pleuritis decreased from 25.4 ± 6.5% in the first period to 5.0 ± 3.7% in the fifth period (p Conclusions The vaccine did not effectively prevent clinical expression of A. pleuropneumoniae infections, but seroconversion to A. pleuropneumoniae in the absence of a SAA-response in a large number pigs indicated that the vaccine had activated the immune
inactivated virus (TPIV), and terr ,walenr DNA (TDNA) vaccines and then challenged at month 8 with live. non-attenuated DENV 3. Reciprocal geometric...method modified from that originally described (Russell er al .. 1967). Vero cell mono layers were seeded in six-well plates (Falcon; Becton...Briefly, microtiter plate wells were coated with purified DENV 2 virions in PBS at 4 oc overnight followed by blocking with 5% non-fat dry milk in PBS
Full Text Available The decline of socio-ecological resilience has emerged as an unprecedented truth with high risks to local and global economies, thereby increasing the vulnerability of businesses and markets while potentially threatening the wellbeing of civil society as a whole. From a business perspective, corporate strategies towards sustainability are crucial to strengthen the social and economic foundations that foster sustainable development. In order to assist enterprises pursuing leading market positions, this work proposes a set of strategic actions towards sustainability and an evaluation scheme to assess the effectiveness of their implementation process. This proposed global strategy encompasses five key sustainability indices—commitment, investment, difficulty, proactivity and vulnerability—focusing the investigation on a sample of enterprises representing the highest consumers of electricity in the state of Rio de Janeiro, Brazil. Addressing the energy consumption, this study also discusses the concerning level of GHG emissions that are associated with the generation of electricity. Although 85% of the enterprises participating in this survey recognized the relevance of the actions proposed, the current degree of proactivity and vulnerability associated with these enterprises indicate that very few of them have effectively implemented and invested in corporate sustainability programs, certainly a symptom of their institutional vulnerability.
Novak, R D; Auvil-Novak, S E
Focus group interviews were performed on 45 intensive care nurses who worked 12-h shifts in a large metropolitan hospital. The purpose of this study was to identify nurses' perceptions of difficulties associated with shiftwork and coping strategies used to combat them. Overall, the findings were not different than those currently discussed in the literature. For example, nurses frequently utilized white noise, telephone answering machines, and light-darkening shades to improve the quality and quantity of day sleep. They also used exercise and increased early shift caffeine consumption to improve night work performance. However, the major incentive for performing night work for these nurses was a high shift differential that equaled approximately 20% of their hourly salary. Most nurses also felt that group educational interventions regarding shiftwork difficulties and coping strategies would be preferred to individual counseling. The most significant finding of this study was the discovery of an extremely high incidence (95%) of automobile-related injuries and near-accidents that occurred while driving to and from the workplace, potentially posing a significant public health risk.
Mitchell, Daniel A J; Dupuy, Lesley C; Sanchez-Lockhart, Mariano; Palacios, Gustavo; Back, Jaap W; Shimanovskaya, Katya; Chaudhury, Sidhartha; Ripoll, Daniel R; Wallqvist, Anders; Schmaljohn, Connie S
We performed epitope mapping studies on the major surface glycoprotein (GP) of Ebola virus (EBOV) using Chemically Linked Peptides on Scaffolds (CLIPS), which form linear and potential conformational epitopes. This method identified monoclonal antibody epitopes and predicted additional epitopes recognized by antibodies in polyclonal sera from animals experimentally vaccinated against or infected with EBOV. Using the information obtained along with structural modeling to predict epitope accessibility, we then constructed two DNA vaccines encoding immunodominant and subdominant epitopes predicted to be accessible on EBOV GP. Although a construct designed to produce a membrane-bound oligopeptide was poorly immunogenic, a construct generating a secreted oligopeptide elicited strong antibody responses in mice. When this construct was administered as a boost to a DNA vaccine expressing the complete EBOV GP gene, the resultant antibody response was focused largely toward the less immunodominant epitopes in the oligopeptide. Taken together, the results of this work suggest a utility for this method for immune focusing of antibody responses elicited by vaccination.
Harmsen, I.A.; Ruiter, R.A.C.; Paulussen, T.G.W.M.; Mollema, L.; Kok, G.; de Melker, H.E.R.
In recent years, parents have become more disparaging towards childhood vaccination. One group that is critical about the National Immunization Program (NIP) and participates less comprises parents with an anthroposophical worldview. Despite the fact that various studies have identified
Knerer, Gerhart; Currie, Christine S M; Brailsford, Sally C
Dengue fever is a vector-borne disease prevalent in tropical and subtropical regions. It is an important public health problem with a considerable and often under-valued disease burden in terms of frequency, cost and quality-of-life. Recent literature reviews have documented the development of mathematical models of dengue fever both to identify important characteristics for future model development as well as to assess the impact of dengue control interventions. Such reviews highlight the importance of short-term cross-protection; antibody-dependent enhancement; and seasonality (in terms of both favourable and unfavourable conditions for mosquitoes). The compartmental model extends work by Bartley (2002) and combines the following factors: seasonality, age-structure, consecutive infection by all four serotypes, cross-protection and immune enhancement, as well as combined vector-host transmission. The model is used to represent dengue transmission dynamics using parameters appropriate for Thailand and to assess the potential impact of combined vector-control and vaccination strategies including routine and catch-up vaccination strategies on disease dynamics. When seasonality and temporary cross-protection between serotypes are included, the model is able to approximate the observed incidence of dengue fever in Thailand. We find vaccination to be the most effective single intervention, albeit with imperfect efficacy (30.2 %) and limited duration of protection. However, in combination, control interventions and vaccination exhibit a marked impact on dengue fever transmission. This study shows that an imperfect vaccine can be a useful weapon in reducing disease spread within the community, although it will be most effective when promoted as one of several strategies for combating dengue fever transmission.
Mo, Annie X Y; Augustine, Alison Deckhut
A highly efficacious vaccine to prevent malaria infection or clinical disease is still far from reality despite several decades of intensive effort and a growing global commitment in malaria vaccine development. Further understanding of the mechanisms required for induction of effective host immune responses and maintenance of long-term protective immunity is needed to facilitate rational approaches for vaccine design and evaluation. The National Institute of Allergy and Infectious Diseases (NIAID) conducted a workshop on June 18-19, 2012 with experts in the fields of malaria vaccine development, malaria immunology, and basic immunology to address issues associated with improving our current understanding of malaria vaccine immunity. This report summarizes the discussion and major recommendations generated by the workshop participants regarding the application of recent advances in basic immunology and state-of-the-art immunological tools to improve progress and help address current challenges and knowledge gaps in malaria vaccine development. Copyright © 2014. Published by Elsevier Ltd. All rights reserved.
Gullberg, Maria; Lohse, Louise; Bøtner, Anette
Foot-and-mouth disease (FMD) is one of the most economically important infectious diseases of production animals globally. Vaccination can help to control this disease, however, current vaccines are imperfect. They are made using chemically inactivated FMD virus (FMDV) that is produced in mammalian......-boost system, using reagents that can be generated outside of high-containment facilities, offers significant advantages to achieve control of FMD by vaccination....
Yu, Shu-Han; Huang, Cheng-Ya
In a postural-suprapostural task, appropriate prioritization is necessary to achieve task goals and maintain postural stability. A "posture-first" principle is typically favored by elderly people in order to secure stance stability, but this comes at the cost of reduced suprapostural performance. Using a postural-suprapostural task with a motor suprapostural goal, this study investigated differences between young and older adults in dual-task cost across varying task prioritization paradigms. Eighteen healthy young (mean age: 24.8 ± 5.2 years) and 18 older (mean age: 68.8 ± 3.7 years) adults executed a designated force-matching task from a stabilometer board using either a stabilometer stance (posture-focus strategy) or force-matching (supraposture-focus strategy) as the primary task. The dual-task effect (DTE: % change in dual-task condition; positive value: dual-task benefit, negative value: dual-task cost) of force-matching error and reaction time (RT), posture error, and approximate entropy (ApEn) of stabilometer movement were measured. When using the supraposture-focus strategy, young adults exhibited larger DTE values in each behavioral parameter than when using the posture-focus strategy. The older adults using the supraposture-focus strategy also attained larger DTE values for posture error, stabilometer movement ApEn, and force-matching error than when using the posture-focus strategy. These results suggest that the supraposture-focus strategy exerted an increased dual-task benefit for posture-motor dual-tasking in both healthy young and elderly adults. The present findings imply that the older adults should make use of the supraposture-focus strategy for fall prevention during dual-task execution.
Autran, Brigitte; Carcelain, Guislaine; Combadiere, Béhazine; Debre, Patrice
Therapeutic vaccines aim to prevent severe complications of a chronic infection by reinforcing host defenses when some immune control, albeit insufficient, can already be demonstrated and when a conventional antimicrobial therapy either is not available or has limited efficacy. We focus on the rationale and challenges behind this still controversial strategy and provide examples from three major chronic infectious diseases-human immunodeficiency virus, hepatitis B virus, and human papillomavirus-for which the efficacy of therapeutic vaccines is currently being evaluated.
Dental caries remains one of the most common global chronic diseases caused by Streptococcus mutans, which is prevalent all over the world. The caries prevalence of children aged between 5-6 years old in China is still in very high rate. A potent and effective anti-caries vaccine has long been expected for caries prevention but no vaccines have been brought to market till now mainly due to the low ability to induce and maintain protective antibody in oral fluids. This review will give a brief historical retrospect on study of dental caries and pathogenesis, effective targets for anti-caries vaccines, oral immune system and immunization against dental caries. Then, salivary IgA antibodies and the protective responses are discussed in the context of the ontogeny of mucosal immunity to indigenous oral streptococcal. The methods and advancement for induction of specific anti-caries salivary sIgA antibodies and enhancement of specific anti-caries salivary sIgA antibodies by intranasal immunization with a safe effective mucosal adjuvant are described. The progress in the enhancement of salivary sIgA antibodies and anti-caries protection by intranasal immunization with flagellin-PAc fusion protein will be highlighted. Finally, some of the main strategies that have been used for successful mucosal vaccination of caries vaccine are reviewed, followed by discussion of the mucosal adjuvant choice for achieving protective immunity at oral mucosal membranes for development of a nasal-spray or nasal-drop anti-caries vaccine for human.
Full Text Available Replacing current refractory treatments for melanoma with new prevention and therapeutic approaches is crucial in order to successfully treat this aggressive cancer form. Melanoma develops from neural crest cells, which express tyrosinase -- a key enzyme in the pigmentation pathway. The tyrosinase enzyme is highly active in melanoma cells and metabolizes polyphenolic compounds; tyrosinase expression thus makes a feasible a target for polyphenol-based therapies. For example, quercetin (3,3′,4′,5,7-pentahydroxyflavone is a highly ubiquitous and well-classified dietary polyphenol found in various fruits, vegetables and other plant products including onions, broccoli, kale, oranges, blueberries, apples, and tea. Quercetin has demonstrated anti-proliferative and pro-apoptotic activity in various cancer cell types. Quercetin is readily metabolized by tyrosinase into various compounds that promote anti-cancer activity; additionally, given that tyrosinase expression increases during tumorigenesis, and its activity is associated with pigmentation changes in both early- and late-stage melanocytic lesions, it suggests that quercetin can be used to target melanoma. In this review we explore the potential of Quercetin as an anti-melanoma agent utilizing and extrapolating on evidence from previous in vitro studies in various human malignant cell lines and propose a four-focus area strategy to develop quercetin as a targeted anti-melanoma compound for use as either a preventative or therapeutic agent. The four areas of focus include utilizing quercetin to i modulate cellular bioreduction potential and associated signaling cascades, ii affect transcription of relevant genes, iii regulate epigenetic processes, and iv develop effective combination therapies and delivery modalities/protocols. In general, quercetin could be used to exploit tyrosinase activity to prevent, and/or treat, melanoma with minimal additional side effects.
J. W. De Jager
Full Text Available Purpose: The purpose of the paper is to determine the levels of satisfaction in respect of pre identified internal marketing-related variables in a large provincial hospital in South Africa. Problem investigated: Low job satisfaction is often cited as a major cause of high turnover among health care providers worldwide. Likewise the Public Health Care Industry in South Africa is facing complex employee retention issues. In determining the reasons for high turnover an interest in evaluating employee satisfaction among health care providers has increased. Measuring components of job satisfaction will assist not only the health care organisations' management to understand hospital culture, but also to compile an effective internal marketing plan and strategy. Design/Methodology/Approach: A staff satisfaction survey was conducted amongst staff members at a provincial hospital in the Tshwane region, South Africa. Attitudes of staff on pre-identified staff satisfaction variables were assessed. These variables were employed to implement an internal marketing strategy. A list of variables was formulated after an extensive literature study had been conducted. A total of 416 staff members voluntarily completed a self-administered questionnaire. A five-point Likert type scale was used to measure the levels of satisfaction on staff-related issues, with a view to addressing issues in the internal marketing strategy. Findings : It was evident that the management principles currently employed by the management team were a cause for concern among staff members. Based on the analysis that identified the satisfaction variables best it was clear that management should take immediate steps to address the following issues : Clarification of hospital goals \\ objectives; Understanding the goals of the respective departments; The functioning of the Human resource department; Functioning of the overall hospital management; andImplications: This paper aims to present a
Platteel, Anouk C M|info:eu-repo/dai/nl/375805613; Marit de Groot, A; Andersen, Peter; Ovaa, Huib; Kloetzel, Peter M; Mishto, Michele; Sijts, Alice J A M|info:eu-repo/dai/nl/115553843
Most vaccines are based on protective humoral responses while for intracellular pathogens CD8(+) T cells are regularly needed to provide protection. However, poor processing efficiency of antigens is often a limiting factor in CD8(+) T cell priming, hampering vaccine efficacy. The multistage cDNA
Since the early 1970s, when serological tests for hepatitis B became available, knowledge of the hepatitis B virus (HBV) has grown rapidly. This virus was among the first to have its genome fully sequenced, and HBV vaccine was among the first to be genetically engineered. Universal HBV vaccination of all newborns ...
Full Text Available Vaccination is one of the most valuable weapons against infectious diseases and has led to a significant reduction in mortality and morbidity. However, for most viral hemorrhagic fevers caused by arenaviruses, no prophylactic vaccine is available. This is particularly problematic as these diseases are notoriously difficult to diagnose and treat. Lassa fever is globally the most important of the fevers caused by arenaviruses, potentially affecting millions of people living in endemic areas, particularly in Nigeria. Annually, an estimated 300,000 humans are infected and several thousands succumb to the disease. The successful development of the vaccine "Candid#1" against Junin virus, the causative agent of Argentine hemorrhagic fever, proved that an effective arenavirus vaccine can be developed. Although several promising studies toward the development of a Lassa fever vaccine have been published, no vaccine candidate has been tested in human volunteers or patients. This review summarizes the immunology and other aspects of existing experimental arenavirus vaccine studies, discusses the reasons for the lack of a vaccine, and proposes a plan for overcoming the final hurdles toward clinical trials.
Full Text Available This paper links professional service firms’ resource-based strategies to their customer-focused performance for formulating service quality improvement priorities. The research applies the structural equation modelling approach to survey data from Hong Kong construction consultants to test some hypotheses. The study validates the various measures of firms’ resource-based strategies and customer-focused performance and bridges the gaps in firms’ organizational learning, core competences and customer-focused performance mediated by their strategic flexibility. The research results have practical implications for professional service firms to deploy resources appropriately to first enhance different competences and then improve customerfocused performance using their different competences.
Full Text Available The present paper aims at investigating the application of an instructional method specifically focused on the expansion of metacognitive awareness and its effect on Serbian EFL students’ listening comprehension. The current study is a follow-up research of a similar study by Vandergrift and Tafaghodtari (2010. However, we sought to expand the previous research by investigating the relationship between the students’ current level of L2 (target language vocabulary and listening test scores. Our study likewise differed in the sample of participants, the target language, teaching and testing material used, and the duration of the very experiment. To answer the proposed research questions we conducted an experiment with 57 Serbian secondary school EFL (English as a Foreign Language learners divided into experimental (n=27 and control group (n=30. The results of the pre- and post-tests of the two groups showed the beneficial effects of developing metacognitive strategies and the strong positive correlation between the level of vocabulary and listening comprehension. The paper underlines important pedagogical implications especially regarding the enhancement of metacognitive awareness and vocabulary proficiency of students in order to improve performance on listening comprehension tasks.
Boklund, Anette; Hisham Beshara Halasa, Tariq; Christiansen, Lasse Engbo
Recent outbreaks of foot-and-mouth disease (FMD) in Europe have highlighted the need for assessment of control strategies to optimise control of the spread of FMD. Our objectives were to assess the epidemiological and financial impact of simulated FMD outbreaks in Denmark and the effect of using...... ring depopulation or emergency vaccination to control these outbreaks. Two stochastic simulation models (InterSpreadPlus (ISP) and the modified Davis Animal Disease Simulation model (DTU-DADS)) were used to simulate the spread of FMD in Denmark using different control strategies.Each epidemic...
Full Text Available Dengue viruses (DENVs cause approximately 390 million cases of DENV infections annually and over 3 billion people worldwide are at risk of infection. No dengue vaccine is currently available nor is there an antiviral therapy for DENV infections. We have developed a tetravalent live-attenuated DENV vaccine (TDV that consists of a molecularly characterized attenuated DENV-2 strain (TDV-2 and three chimeric viruses containing the pre-membrane and envelope genes of DENV-1, -3 and -4 expressed in the context of the TDV-2 genome. To impact dengue vaccine delivery in endemic areas and immunize travelers, a simple and rapid immunization strategy (RIS is preferred. We investigated RIS consisting of two full vaccine doses being administered subcutaneously or intradermally on the initial vaccination visit (day 0 at two different anatomical locations with a needle-free disposable syringe jet injection (DSJI delivery devices (PharmaJet in non-human primates (NHP. This vaccination strategy resulted in efficient priming and induction of neutralizing antibody responses to all four DENV serotypes comparable to those elicited by the traditional prime and boost (two months later vaccination schedule. In addition, the vaccine induced CD4+ and CD8+ T cells producing IFN-γ, IL-2, and TNF-α, and targeting the DENV-2 NS1, NS3 and NS5 proteins. Moreover, vaccine-specific T cells were cross-reactive with the non-structural NS3 and NS5 proteins of DENV-4. When animals were challenged with DENV-2 they were protected with no detectable viremia, and exhibited sterilizing immunity (no increase of neutralizing titers post- challenge. RIS could decrease vaccination visits and provide quick immune response to all four DENV serotypes. This strategy could increase vaccination compliance and would be especially advantageous for travelers into endemic areas.
Honglei SUN,Jinhua LIU
Full Text Available Vaccination for highly pathogenic avian influenza (HPAI has been implemented in China for a decade, however, the virus is still present in poultry. A series of recombinant vaccines, Re-1 to Re-7, have been developed and used, and Re-8 will also be used in clinical settings to prevent the prevailing flu strains. The question remains, when can China eradicate the disease? Here, we review the epidemiology of H5 HPAI along with the development, usage and problems of vaccines. Further suggestions for controlling the disease in China are provided.
Pandey, Manisha; Mortensen, Rasmus; Calcutt, Ainslie
Cluster of virulence responder/sensor (CovR/S) mutant group A streptococci (GAS) are serious human pathogens of multiple M protein strains that upregulate expression of virulence factors, including the IL-8 protease Streptococcus pyogenes cell envelope proteinase (SpyCEP), thus blunting neutrophil......-mediated killing and enabling ingress of bacteria from a superficial wound to deep tissue.We previously showed that a combination vaccine incorporating J8-DT (conserved peptide vaccine from theM protein) and a recombinant SpyCEP fragment protects against CovR/S mutants. To enhance the vaccine's safety profile, we...
Full Text Available Effective reading is essential for success in learning a foreign language. EFL learners, therefore, need to master a number of reading strategies to be able to comprehend text information. Strategic reading research has already evidenced the possibility of teaching comprehension strategies to enhance learner’ comprehension and metacognitive abilities. Further research is needed though to examine the procedures or methodologies through which the approach can be applied. This pretest-posttest quasi-experimental article aimed, firstly, to compare the effects of the two widespread methods of explicit teaching of comprehension strategies (focused vs. multiple on EFL learner’ reading comprehension and lexical development and, secondly, to explore whether or not integration of fixed and multiple instructional techniques significantly improved intermediate EFL learners reading comprehension ability and lexical knowledge. To this end, four intact classes including 69 intermediate EFL learners in a language center in Isfahan were randomly assigned to one control and three experimental groups. The groups received the same amount of instruction, however differently, three receiving focused, multiple, and integrated strategy interventions respectively and the other receiving conventional reading-based instruction. The results revealed that while receiving focused strategy intervention did not offer a statistically significant advantage over the typical classroom setting, benefiting from multiple strategy intervention significantly improved the learners’ ability in reading comprehension. Moreover, the results asserted the efficacy of integrated strategy instruction in improving both reading comprehension and lexical development among Iranian intermediate EFL learners.
Burley, Claire V; Bailey, Damian M; Marley, Christopher J; Lucas, Samuel J E
The prevalence of cognitive decline and neurodegenerative diseases (e.g. stroke and dementia) is increasing. Numerous studies show that regular exercise has beneficial effects on brain health in clinical and non-clinical populations, yet adherence to public health exercise guidelines is notoriously poor. Recently, novel exercise strategies have been investigated to allow for more individualised and prescriptive approaches that target the key mechanistic pathways that allow exercise to mediate adaptation. This work exploring alternative approaches to the traditional model of exercise training has demonstrated exciting potential for positive health-related adaptations (especially for metabolic, muscle and cardiovascular function). However, few studies to date have focused on brain adaptations. The aim of this review is to summarise new and innovative interventions that have the potential to optimise exercise for improved brain health (i.e., brain structure and function). First, we will briefly summarise current understanding of the nature whereby positive effects of exercise deliver their influence on the brain (i.e., underlying mechanisms and factors affecting its delivery). We will then introduce the effects of exercise training on cognition and give examples of studies showing the beneficial effects of exercise in clinical populations. Finally, we will explore the adaptive roles of individual stressors that may induce greater health-related adaptations in the brain than exercise alone, including environmental stressors (hydrostatic stress, thermal stress and hypoxia), nutritional supplementation and cognitive loading. In summary, optimised interventions that target key mechanistic pathways linked to improved brain structure and function could ultimately protect against and/or ameliorate cognitive decline and neurodegenerative diseases. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
Liu, Yuchun; Chan, Jerry K Y; Teoh, Swee-Hin
Poor angiogenesis within tissue-engineered grafts has been identified as a main challenge limiting the clinical introduction of bone tissue-engineering (BTE) approaches for the repair of large bone defects. Thick BTE grafts often exhibit poor cellular viability particularly at the core, leading to graft failure and lack of integration with host tissues. Various BTE approaches have been explored for improving vascularisation in tissue-engineered constructs and are briefly discussed in this review. Recent investigations relating to co-culture systems of endothelial and osteoblast-like cells have shown evidence of BTE efficacy in increasing vascularization in thick constructs. This review provides an overview of key concepts related to bone formation and then focuses on the current state of engineered vascularized co-culture systems using bone repair as a model. It will also address key questions regarding the generation of clinically relevant vascularized bone constructs as well as potential directions and considerations for research with the objective of pursuing engineered co-culture systems in other disciplines of vascularized regenerative medicine. The final objective is to generate serious and functional long-lasting vessels for sustainable angiogenesis that will enable enhanced cellular survival within thick voluminous bone grafts, thereby aiding in bone formation and remodelling in the long term. However, more evidence about the quality of blood vessels formed and its associated functional improvement in bone formation as well as a mechanistic understanding of their interactions are necessary for designing better therapeutic strategies for translation to clinical settings. Copyright © 2012 John Wiley & Sons, Ltd.
Sok, J; Hogeveen, H; Elbers, A R W; Oude Lansink, A G J M
Understanding the context and drivers of farmers' decision-making is critical to designing successful voluntary disease control interventions. This study uses a questionnaire based on the Reasoned Action Approach framework to assess the determinants of farmers' intention to participate in a hypothetical reactive vaccination scheme against Bluetongue. Results suggest that farmers' attitude and social pressures best explained intention. A mix of policy instruments can be used in a complementary way to motivate voluntary vaccination based on the finding that participation is influenced by both internal and external motivation. Next to informational and incentive-based instruments, social pressures, which stem from different type of perceived norms, can spur farmers' vaccination behaviour and serve as catalysts in voluntary vaccination schemes. Copyright © 2016 Elsevier B.V. All rights reserved.
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
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
Xiao-Min Hu; Jun Zhang; Haihong Chen
Vaccination is one of the effective ways for protecting susceptible individuals from infectious diseases. Different age groups of population have different vulnerability to the disease and different contact frequencies. In order to achieve the maximum effects, the distribution of vaccine doses to the groups of individuals needs to be optimized. In this paper, a differential evolution (DE) algorithm is proposed to address the problem. The performance of the proposed algorithm has been tested b...
La Torre, Giuseppe; Miccoli, Silvia; Ricciardi, Walter
The Italian Alliance of vaccination strategies project was born with the aim of informing healthcare workers and the general population about vaccination through Facebook. The evaluation of the account has been carried out using 3 indicators: friend membership, numbers of "I like," and amount of "share" of contents for type of news and for day of the week. The survey was performed on 743 users. Institutional events were the most popular type of news; the day of the week in which users were most likely to be attracted by links was Friday. Press releases were the communication form most shared by users. Social media marketing carries the advantages of low cost, rapid transmission and user interaction.
Barrios, Kelly; Celis, Esteban
Background Therapeutic vaccines for cancer are an attractive alternative to conventional therapies, since the later result in serious adverse effects and in most cases are not effective against advanced disease. Human Papillomavirus (HPV) is responsible for several malignancies such as cervical carcinoma. Vaccines targeting oncogenic viral proteins like HPV16-E6 and -E7 are ideal candidates to elicit strong immune responses without generating autoimmunity because: i) these products are not expressed in normal cells; and ii) their expression is required to maintain the malignant phenotype. Our group has developed peptide vaccination strategy called TriVax, which is effective in generating vast numbers of antigen-specific T cells in mice capable of persisting for long time periods. Materials and methods We have used two HPV-induced mouse cancer models (TC-1 and C3.43) to evaluate the immunogenicity and therapeutic efficacy of TriVax prepared with the immunodominant CD8 T cell epitope HPV16-E749–57, mixed with poly-IC adjuvant and costimulatory anti-CD40 antibodies. Results TriVax using HPV16-E749–57 induced large and persistent T cell responses that were therapeutically effective against established HPV16-E7 expressing tumors. In most cases, TriVax was successful in attaining complete rejections of 6–11 day established tumors. In addition, TriVax induced long-term immunological memory, which prevented tumor recurrences. The antitumor effects of TriVax were independent of NK and CD4 T cells and surprisingly, did not rely to a great extent on type-I or type-II interferon. Conclusions These findings indicate that the TriVax strategy is an appealing immunotherapeutic approach for the treatment of established viral-induced tumors. We believe that these studies may help to launch more effective and less invasive therapeutic vaccines for HPV-mediated malignancies. PMID:22527249
Barrios, Kelly; Celis, Esteban
Therapeutic vaccines for cancer are an attractive alternative to conventional therapies, since the later result in serious adverse effects and in most cases are not effective against advanced disease. Human papillomavirus (HPV) is responsible for several malignancies such as cervical carcinoma. Vaccines targeting oncogenic viral proteins like HPV16-E6 and HPV16-E7 are ideal candidates to elicit strong immune responses without generating autoimmunity because: (1) these products are not expressed in normal cells and (2) their expression is required to maintain the malignant phenotype. Our group has developed peptide vaccination strategy called TriVax, which is effective in generating vast numbers of antigen-specific T cells in mice capable of persisting for long time periods. We have used two HPV-induced mouse cancer models (TC-1 and C3.43) to evaluate the immunogenicity and therapeutic efficacy of TriVax prepared with the immunodominant CD8 T-cell epitope HPV16-E7(49-57), mixed with poly-IC adjuvant and costimulatory anti-CD40 antibodies. TriVax using HPV16-E7(49-57) induced large and persistent T-cell responses that were therapeutically effective against established HPV16-E7 expressing tumors. In most cases, TriVax was successful in attaining complete rejections of 6-11-day established tumors. In addition, TriVax induced long-term immunological memory, which prevented tumor recurrences. The anti-tumor effects of TriVax were independent of NK and CD4 T cells and, surprisingly, did not rely to a great extent on type-I or type-II interferon. These findings indicate that the TriVax strategy is an appealing immunotherapeutic approach for the treatment of established viral-induced tumors. We believe that these studies may help to launch more effective and less invasive therapeutic vaccines for HPV-mediated malignancies.
Ellsäßer, G; Trost-Brinkhues, G
In Germany, surveillance of the population's immunisation is only mandatory for school beginners, not for adolescents. Therefore, no current data are available from the public health service related to the immunisation of adolescents. Also lacking are nationwide monitoring data regarding HPV vaccination among girls aged 12-18 years and the meningococcal C vaccination, both recently introduced by the German Standing Committee on Vaccination (STIKO) in 2009 and 2006, respectively. The present research and analysis therefore aims to determine which German states perform a monitoring of the vaccination status of adolescents, how immunisation rates differ across German states and what need for action, in terms of a nationwide immunisation strategy, can be derived. A systematic survey of vaccination coverage among students in grades 6-10 (age group 12-16 years) for the school year 2010/11 was undertaken. The defined documentation standard is based on the standard vaccinations for children and adolescents according to STIKO, requiring complete primary immunization (PI) and the number of booster vaccinations. In the analysis, 8 of 16 states were included, due to lack of data for the remaining states. In total, the public health service -examined 157,599 school children in 8 German states and checked 103,250 vaccination certificates (on average 68.1%, range 54.9-85.2%). The implementation of the booster vaccination among students in grades 6-10 proved to be insufficient. The 2-dose measles vaccination, required by the WHO for 95% of the population, was only nearly achieved by 2 of 8 German states -(Saxony-Anhalt, Brandenburg). The effects of insufficient immunisation coverage are shown by, for example, a higher measles incidence rate in children under 15 years and a persisting peak of pertussis incidence in 10- to 15-year-olds. The meningococcal C vaccination, introduced in 2006, was insufficiently taken up by students and very differently implemented among the 8 -German
Odéen, Henrik, E-mail: email@example.com; Diakite, Mahamadou [Department of Physics and Astronomy, University of Utah, Salt Lake City, Utah 84108 and Department of Radiology, University of Utah, Salt Lake City, Utah 84108 (United States); Todd, Nick; Minalga, Emilee; Payne, Allison; Parker, Dennis L. [Department of Radiology, University of Utah, Salt Lake City, Utah 84108 (United States)
Purpose: To investigate k-space subsampling strategies to achieve fast, large field-of-view (FOV) temperature monitoring using segmented echo planar imaging (EPI) proton resonance frequency shift thermometry for MR guided high intensity focused ultrasound (MRgHIFU) applications. Methods: Five different k-space sampling approaches were investigated, varying sample spacing (equally vs nonequally spaced within the echo train), sampling density (variable sampling density in zero, one, and two dimensions), and utilizing sequential or centric sampling. Three of the schemes utilized sequential sampling with the sampling density varied in zero, one, and two dimensions, to investigate sampling the k-space center more frequently. Two of the schemes utilized centric sampling to acquire the k-space center with a longer echo time for improved phase measurements, and vary the sampling density in zero and two dimensions, respectively. Phantom experiments and a theoretical point spread function analysis were performed to investigate their performance. Variable density sampling in zero and two dimensions was also implemented in a non-EPI GRE pulse sequence for comparison. All subsampled data were reconstructed with a previously described temporally constrained reconstruction (TCR) algorithm. Results: The accuracy of each sampling strategy in measuring the temperature rise in the HIFU focal spot was measured in terms of the root-mean-square-error (RMSE) compared to fully sampled “truth.” For the schemes utilizing sequential sampling, the accuracy was found to improve with the dimensionality of the variable density sampling, giving values of 0.65 °C, 0.49 °C, and 0.35 °C for density variation in zero, one, and two dimensions, respectively. The schemes utilizing centric sampling were found to underestimate the temperature rise, with RMSE values of 1.05 °C and 1.31 °C, for variable density sampling in zero and two dimensions, respectively. Similar subsampling schemes
Odéen, Henrik; Todd, Nick; Diakite, Mahamadou; Minalga, Emilee; Payne, Allison; Parker, Dennis L.
Purpose: To investigate k-space subsampling strategies to achieve fast, large field-of-view (FOV) temperature monitoring using segmented echo planar imaging (EPI) proton resonance frequency shift thermometry for MR guided high intensity focused ultrasound (MRgHIFU) applications. Methods: Five different k-space sampling approaches were investigated, varying sample spacing (equally vs nonequally spaced within the echo train), sampling density (variable sampling density in zero, one, and two dimensions), and utilizing sequential or centric sampling. Three of the schemes utilized sequential sampling with the sampling density varied in zero, one, and two dimensions, to investigate sampling the k-space center more frequently. Two of the schemes utilized centric sampling to acquire the k-space center with a longer echo time for improved phase measurements, and vary the sampling density in zero and two dimensions, respectively. Phantom experiments and a theoretical point spread function analysis were performed to investigate their performance. Variable density sampling in zero and two dimensions was also implemented in a non-EPI GRE pulse sequence for comparison. All subsampled data were reconstructed with a previously described temporally constrained reconstruction (TCR) algorithm. Results: The accuracy of each sampling strategy in measuring the temperature rise in the HIFU focal spot was measured in terms of the root-mean-square-error (RMSE) compared to fully sampled “truth.” For the schemes utilizing sequential sampling, the accuracy was found to improve with the dimensionality of the variable density sampling, giving values of 0.65 °C, 0.49 °C, and 0.35 °C for density variation in zero, one, and two dimensions, respectively. The schemes utilizing centric sampling were found to underestimate the temperature rise, with RMSE values of 1.05 °C and 1.31 °C, for variable density sampling in zero and two dimensions, respectively. Similar subsampling schemes
Abbasian, Gholam-Reza; Hartoonian, Anahid
Self-regulated learning strategies have recently received a remarkable attention by researchers. The aim of this study was to explore the relationship between self-regulated learning strategies and students' language proficiency as well as their reading comprehension. To do so, 115 Iranian EFL university students were selected. First, a TOEFL test…
Metacognitive reading strategies were trained and practiced using interactive Web-based tools. Twenty middle school poor reading comprehenders were trained in two metacognitive strategies using a Web-based application called 3D-Readers. The training texts were science-oriented and merged the
Full Text Available Mother-to-child transmission (MTCT is an important way of hepatitis B virus (HBV transmission. Blocking the HBV MTCT has a great significance for the prevention and treatment of hepatitis B. This article reviews the current blocking strategies implemented in the antepartum, peripartum, and postpartum stages, and summarizes the controversies existing in the blocking strategies in different stages. The significance of HBV occult infection and germ cell transmission in the HBV MTCT is analyzed. The results indicate that the current strategies for the prevention of hepatitis B MTCT need further improvement. Attentions should be focused on HBV occult infection and germ cell transmission.
Full Text Available Abstract Background Although there is rapid progress in vaccine research regarding influenza pandemic vaccines it is expected that pandemic influenza vaccine production can only start once the pandemic virus has been recognized. Therefore, pandemic vaccine capacity will be limited at least during the first phase of an influenza pandemic, requiring vaccine prioritization strategies. WHO recommends developing preliminary priorities for pandemic vaccine use. The goal of this review is to provide a thorough overview of pandemic vaccine prioritization concepts in the 27 European Union (EU member states and the four non-EU countries of the Global Health Security Action Group. Methods Between September and December 2006 data was collected for each country through two data sources: (i the national influenza pandemic plan; (ii contacting key persons involved in pandemic planning by email and/or phone and/or fax Results Twenty-six (84% countries had established at least one vaccine priority group. Most common reported vaccine priority groups were health care workers (HCW (100%, essential service providers (ESP (92% and high risk individuals (HRI (92%. Ranking of at least one vaccine priority group was done by 17 (65% of 26 countries. Fifteen (88% of these 17 countries including a ranking strategy, decided that HCW with close contact to influenza patients should be vaccinated first; in most countries followed and/or ranked equally by ESP and subsequently HRI. Rationales for prioritization were provided by 22 (85% of 26 countries that established vaccine priority groups. There was large variation in the phrasing and level of detailed specification of rationales. Seven (32% of 22 countries providing rationales clearly associated each vaccine priority group with the specific rationale. Ten (32% of the 31 countries studied countries have consulted and involved ethical experts to guide decisions related to vaccine prioritization. Conclusion In the majority of
Background Pricing strategies are mentioned frequently as a potentially effective tool to stimulate healthy eating, mainly for consumers with a low socio-economic status. Still, it is not known how these consumers perceive pricing strategies, which pricing strategies are favoured and what contextual factors are important in achieving the anticipated effects. Methods We conducted seven focus groups among 59 residents of deprived neighbourhoods in two large Dutch cities. The focus group topics were based on insights from Rogers' Diffusion of Innovations Theory and consisted of four parts: 1) discussion on factors in food selection; 2) attitudes and perceptions towards food prices; 3) thinking up pricing strategies; 4) attitudes and perceptions regarding nine pricing strategies that were nominated by experts in a former Delphi Study. Analyses were conducted with Atlas.ti 5.2 computer software, using the framework approach. Results Qualitative analyses revealed that this group of consumers consider price to be a core factor in food choice and that they experience financial barriers against buying certain foods. Price was also experienced as a proficient tool to stimulate healthier food choices. Yet, consumers indicated that significant effects could only be achieved by combining price with information and promotion techniques. In general, pricing strategies focusing on encouraging healthy eating were valued to be more helpful than pricing strategies which focused on discouraging unhealthy eating. Suggested high reward strategies were: reducing the price of healthier options of comparable products (e.g., whole meal bread) compared to unhealthier options (e.g., white bread); providing a healthy food discount card for low-income groups; and combining price discounts on healthier foods with other marketing techniques such as displaying cheap and healthy foods at the cash desk. Conclusion This focus group study provides important new insights regarding the use of pricing
Seidell Jacob C
Full Text Available Abstract Background Pricing strategies are mentioned frequently as a potentially effective tool to stimulate healthy eating, mainly for consumers with a low socio-economic status. Still, it is not known how these consumers perceive pricing strategies, which pricing strategies are favoured and what contextual factors are important in achieving the anticipated effects. Methods We conducted seven focus groups among 59 residents of deprived neighbourhoods in two large Dutch cities. The focus group topics were based on insights from Rogers' Diffusion of Innovations Theory and consisted of four parts: 1 discussion on factors in food selection; 2 attitudes and perceptions towards food prices; 3 thinking up pricing strategies; 4 attitudes and perceptions regarding nine pricing strategies that were nominated by experts in a former Delphi Study. Analyses were conducted with Atlas.ti 5.2 computer software, using the framework approach. Results Qualitative analyses revealed that this group of consumers consider price to be a core factor in food choice and that they experience financial barriers against buying certain foods. Price was also experienced as a proficient tool to stimulate healthier food choices. Yet, consumers indicated that significant effects could only be achieved by combining price with information and promotion techniques. In general, pricing strategies focusing on encouraging healthy eating were valued to be more helpful than pricing strategies which focused on discouraging unhealthy eating. Suggested high reward strategies were: reducing the price of healthier options of comparable products (e.g., whole meal bread compared to unhealthier options (e.g., white bread; providing a healthy food discount card for low-income groups; and combining price discounts on healthier foods with other marketing techniques such as displaying cheap and healthy foods at the cash desk. Conclusion This focus group study provides important new insights
Hongu, Nobuko; Kataura, Martha P.; Block, Linda M.
This article helps Extension professionals guide individuals in a successful long-term weight loss program. A program should focus on behavioral changes (improving eating habits and physical activity), not just weight loss. In order to do this, Extension professionals should implement behavior change strategies that motivate individuals to…
Fidalgo, R.; Torrance, M.; Rijlaarsdam, G.; van den Bergh, H.; Álvarez, M.L.
Three groups of typically-developing 6th grade students (total N = 62) each completed strategy-focused writing training. Using a combined lagged-group and cross-panel design we assessed the effectiveness of a sequence of four different instructional components: observation and group reflection on a
Nizard, Mevyn; Diniz, Mariana O; Roussel, Helene; Tran, Thi; Ferreira, Luis Cs; Badoual, Cecile; Tartour, Eric
The mucosal immune system displays several adaptations reflecting the exposure to the external environment. The efficient induction of mucosal immune responses also requires specific approaches, such as the use of appropriate administration routes and specific adjuvants and/or delivery systems. In contrast to vaccines delivered via parenteral routes, experimental, and clinical evidences demonstrated that mucosal vaccines can efficiently induce local immune responses to pathogens or tumors located at mucosal sites as well as systemic response. At least in part, such features can be explained by the compartmentalization of mucosal B and T cell populations that play important roles in the modulation of local immune responses. In the present review, we discuss molecular and cellular features of the mucosal immune system as well as novel immunization approaches that may lead to the development of innovative and efficient vaccines targeting pathogens and tumors at different mucosal sites.
Full Text Available Dengue virus (DENV is a major public health threat worldwide. A key element in protection from dengue fever is the neutralising antibody response. Anti-dengue IgG purified from DENV-2 infected human sera showed reactivity against several peptides when evaluated by ELISA and epitope extraction techniques. A multi-step computational approach predicted six antigenic regions within the E protein of DENV-2 that concur with the 6 epitopes identified by the combined ELISA and epitope extraction approach. The selected peptides representing B-cell epitopes were attached to a known dengue T-helper epitope and evaluated for their vaccine potency. Immunization of mice revealed two novel synthetic vaccine constructs that elicited good humoral immune responses and produced cross-reactive neutralising antibodies against DENV-1, 2 and 3. The findings indicate new directions for epitope mapping and contribute towards the future development of multi-epitope based synthetic peptide vaccine.
Mason, Chase M; Donovan, Lisa A
Leaf defenses have long been studied in the context of plant growth rate, resource availability, and optimal investment theory. Likewise, one of the central modern paradigms of plant ecophysiology, the leaf economics spectrum (LES), has been extensively studied in the context of these factors across ecological scales ranging from global species data sets to temporal shifts within individuals. Despite strong physiological links between LES strategy and leaf defenses in structure, function, and resource investment, the relationship between these trait classes has not been well explored. This study investigates the relationship between leaf defenses and LES strategy across whole-plant ontogeny in three diverse Helianthus species known to exhibit dramatic ontogenetic shifts in LES strategy, focusing primarily on physical and quantitative chemical defenses. Plants were grown under controlled environmental conditions and sampled for LES and defense traits at four ontogenetic stages. Defenses were found to shift strongly with ontogeny, and to correlate strongly with LES strategy. More advanced ontogenetic stages with more conservative LES strategy leaves had higher tannin activity and toughness in all species, and higher leaf dry matter content in two of three species. Modeling results in two species support the conclusion that changes in defenses drive changes in LES strategy through ontogeny, and in one species that changes in defenses and LES strategy are likely independently driven by ontogeny. Results of this study support the hypothesis that leaf-level allocation to defenses might be an important determinant of leaf economic traits, where high investment in defenses drives a conservative LES strategy.
Pertussis is a bacterial disease, benign in adults, but with a high morbidity and mortality index in newborn infants. Early diagnosis and treatment, using appropriate antibiotics and hospital care, enabled to reduce the seriousness of the disease. However, the bacteria keeps on circulating with recurrent epidemic peaks.Since 2004, the Cocoon Strategy aims to vaccinate the relatives of newborn infants, so as to protect them before they get their first vaccines.We made a descriptive transversal...
Full Text Available 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 < 0.05 in the immune response levels were observed between probiotics expressing the COE-DCpep fusion protein and COE antigen alone, suggesting better immune efficiency of the probiotics vaccine expressing the DC-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.
Full Text Available Tumor vaccines have held much promise, but to date have demonstrated little clinical success. This lack of success is conceivably due to poor tumor antigen presentation combined with immuno-suppressive mechanisms exploited by the tumor itself. Knock down of Inhibitor of differentiation protein 2 (Id2-kd in mouse neuroblastoma whole tumor cells rendered these cells immunogenic. Id2-kd neuroblastoma (Neuro2a cells (Id2-kd N2a failed to grow in most immune competent mice and these mice subsequently developed immunity against further wild-type Neuro2a tumor cell challenge. Id2-kd N2a cells grew aggressively in immune-compromised hosts, thereby establishing the immunogenicity of these cells. Therapeutic vaccination with Id2-kd N2a cells alone suppressed tumor growth even in established neuroblastoma tumors and when used in combination with immune checkpoint blockade eradicated large established tumors. Mechanistically, immune cell depletion studies demonstrated that while CD8+ T cells are critical for antitumor immunity, CD4+ T cells are also required to induce a sustained long-lasting helper effect. An increase in number of CD8+ T-cells and enhanced production of interferon gamma (IFNγ was observed in tumor antigen stimulated splenocytes of vaccinated mice. More importantly, a massive influx of cytotoxic CD8+ T-cells infiltrated the shrinking tumor following combined immunotherapy. These findings show that down regulation of Id2 induced tumor cell immunity and in combination with checkpoint blockade produced a novel, potent, T-cell mediated tumor vaccine strategy.
Hafner, Louise M; Timms, Peter
The "cloaked" bacterial pathogen that is Chlamydia trachomatis continues to cause sexually transmitted infections (STIs) that adversely affect the health and well-being of children, adolescents and adults globally. The reproductive disease sequelae follow unresolved or untreated chronic or recurrent asymptomatic C.trachomatis infections of the lower female genital tract (FGT) and can include pelvic pain, pelvic inflammatory disease (PID) and ectopic pregnancy. Tubal Factor Infertility (TFI) can also occur since protective and long-term natural immunity to chlamydial infection is incomplete, allowing for ascension of the organism to the upper FGT. Developing countries including the WHO African (8.3 million cases) and South-East Asian regions (7.2 million cases) bear the highest burden of chlamydial STIs. Areas covered: Genetic advances for Chlamydia have provided tools for transformation (including dendrimer-enabled transformation), lateral gene transfer and chemical mutagenesis. Recent progress in these areas is reviewed with a focus on vaccine development for Chlamydia infections of the female genital tract. Expert commentary: A vaccine that can elicit immuno-protective responses whilst avoiding adverse immuno-pathologic host responses is required. The current technological advances in chlamydial genetics and proteomics, as well as novel and improved adjuvants and delivery systems, provide new hope that the elusive chlamydial vaccine is an imminent and realistic goal.
Svendsen, Erik R; Yamaguchi, Ichiro; Tsuda, Toshihide; Guimaraes, Jean Remy Davee; Tondel, Martin
It has been difficult to both mitigate the health consequences and effectively provide health risk information to the public affected by the Fukushima radiological disaster. Often, there are contrasting public health ethics within these activities which complicate risk communication. Although no risk communication strategy is perfect in such disasters, the ethical principles of risk communication provide good practical guidance. These discussions will be made in the context of similar lessons learned after radiation exposures in Goiania, Brazil, in 1987; the Chernobyl nuclear power plant accident, Ukraine, in 1986; and the attack at the World Trade Center, New York, USA, in 2001. Neither of the two strategies is perfect nor fatally flawed. Yet, this discussion and lessons from prior events should assist decision makers with navigating difficult risk communication strategies in similar environmental health disasters.
Rhodes, Scott D; Yee, Leland J
An understanding of vaccine acceptance and uptake is imperative for successful vaccination of populations that will be primary targets for vaccination after a vaccine against HIV is developed and ready for dissemination. Experiences with vaccination against vaccine-preventable hepatitis (VPH) among men who have sex with men (MSM) may offer key insights to inform future HIV vaccination strategies. The purpose of this analysis was to explore what is known currently about vaccination among MSM, using knowledge gained from vaccination against VPH, and to identify important considerations from these experiences that must be explored further as a vaccine against HIV is promoted among MSM. Because cultural and political differences make it difficult to extrapolate findings from studies in one country to another, we have focused our analyses on studies conducted in the USA. Through a qualitative systematic review of published reports, we identified eight studies that reported correlates of VPH among MSM in the USA. Six major domains of variables associated with vaccination against VPH were identified, including: demographics (e.g. younger age, higher educational attainment); increased vaccine knowledge; increased access to health care; provider recommendation; behaviours (e.g. same-sex behaviour, health-promoting and disease-preventing behaviours); and psychosocial factors (e.g. openness about one's sexual orientation, reduced barriers to being vaccinated, self-efficacy). Further research is needed to understand vaccination behaviour among MSM and to maximise acceptance and uptake after a vaccine exists. Experiences with VPH provide a real-world model on which to base preliminary assumptions about acceptance and uptake of a vaccine against HIV.
Full Text Available One of the most controversial issues in applied linguistics over the past two decades concerns the role of conscious and unconscious processes in second language learning. On the other hand, many researchers believe that focusing on the target language system is necessary if learners are to produce language forms. However, what remains missing in the literature of focus on form is the effect of the degree of noticing and attention (intensive/extensive on EFL learners’ oral/written production. Thus, the main purpose of the present study is to investigate the effect of intensive and extensive focus on form on EFL learners’ oral production. To this end, 40 learners of English at pre-intermediate level were chosen randomly as the participants of the study and assigned into two groups of intensive and extensive. They received 20 sessions of intensive and extensive form-focused instructions. A narrative task and a delayed focused and unfocused task were employed to collect data from the participants. The collected oral data was quantified in terms of the accuracy measure. Independent Samples T-test was employed as the statistical means of analysis. The results of the study revealed no differences between the performances of two groups in terms of the accuracy in oral narrative task. However, the result of statistical analysis for the delayed post-test in focused intensive task was significant. The study might carry some pedagogical implications for second language teachers, SLA researchers, teacher education and task designers.
Full Text Available Here, we report the construction of a vaccine against lymphocystis disease virus (LCDV using nucleic acid vaccination technology. A fragment of the major capsid protein encoding gene from an LCDV isolated from China (LCDV-cn was cloned into an eukaryotic expression vector pEGFP-N2, yielding a recombinant plasmid pEGFP-N2-LCDV-cn0.6 kb. This plasmid was immediately expressed after liposomal transfer into the Japanese flounder embryo cell line. The recombinant plasmid was inoculated into Japanese flounder via two routes (intramuscular injection and hypodermic injection at three doses (0.1, 5, and 15 μg, and then T-lymphopoiesis in different tissues and antibodies raised against LCDV were evaluated. The results indicated that this recombinant plasmid induced unique humoral or cell-mediated immune responses depending on the inoculation route and conferred immune protection. Furthermore, the humoral immune responses and protective effects were significantly increased at higher vaccine doses via the two injection routes. Plasmid pEGFP-N2-LCDV0.6 kb is therefore a promising vaccine candidate against LCDV in Japanese flounder.
Cawley, John; Hull, Harry F.; Rousculp, Matthew D.
Background: The Advisory Committee on Immunization Practices (ACIP) recommends influenza vaccinations for all children 6 months to 18 years of age, which includes school-aged children. Influenza immunization programs may benefit schools by reducing absenteeism. Methods: A systematic literature review of PubMed, PsychLit, and Dissertation Abstracts…
Vaccines against avian influenza (AI) have had limited use in poultry until 2002, when the H5N1 high pathogenicity avian influenza (HPAI) spread from China to Hong Kong, and then multiple southeast Asian countries in 2003-2004, and to Europe in 2005, and Africa in 2006. Over the past 40 years, AI ...
Wit GA de; Welte R; CZO
National and international economic evaluations of universal vaccination against hepatitis B were systematically selected from the literature. Only the studies meeting the following criteria were selected: (a) original data reported in Dutch, English, French or German; (b) at least one universal
de la Fuente, J.; Kopáček, Petr; Lew-Tabor, A.; Maritz-Olivier, C.
Roč. 38, č. 12 (2016), s. 754-769 ISSN 0141-9838 R&D Projects: GA ČR GA13-11043S EU Projects: European Commission(XE) 278976 - ANTIGONE Institutional support: RVO:60077344 Keywords : interactomics * reverse genetics * systems biology * tick * vaccine * vaccinology Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.493, year: 2016
Frey, Sharon E; Winokur, Patricia L; Salata, Robert A; El-Kamary, Samer S; Turley, Christine B; Walter, Emmanuel B; Hay, Christine Mhorag; Newman, Frances K; Hill, Heather R; Zhang, Ying; Chaplin, Paul; Tary-Lehmann, Magdalena; Belshe, Robert B
Reintroduction of Variola major as an agent of bioterrorism remains a concern. A shortened dosing schedule of Bavarian Nordic's (BN) IMVAMUNE(®) (modified vaccinia Ankara vaccine against smallpox) was compared to the currently recommended 0- and 28-day schedule for non-inferiority by evaluating the magnitude and kinetics of the immune responses. Subjects were assigned to receive IMVAMUNE or placebo administered subcutaneously on Days 0 and 7, Days 0 and 28, or Day 0. Blood was collected for antibody and cell-mediated immune assays. Subjects were followed for safety for 12 months after last vaccination. The primary endpoint of this study was the geometric mean antibody titers (GMT) at 14 days post last vaccination. Of 208 subjects enrolled, 191 received vaccine (Group: 0+7, Group: 0+28 and Group: 0) and 17 received placebo. Moderate/severe systemic reactogenicity after any vaccination were reported by 31.1%, 25.4%, and 28.6% of the subjects for Group: 0+7, Group: 0+28, and Group: 0, respectively (Chi-square test, P=0.77). Based on BN's Plaque Reduction Assay GMTs, Group: 0+7 was non-inferior to Group: 0+28 at Day 4, 180, and 365 after the second vaccination. On Day 14, Group: 0+7 and Group: 0+28 GMT were 10.8 (CI: 9.0, 12.9) and 30.2 (CI: 22.1, 41.1), respectively. Based on BN's Enzyme-linked immunosorbent assay, the proportion of subjects with positive titers for Group: 0+28 was significantly greater than that for Group: 0+7 after second vaccination at Days 4 and 180. By Day 14 after the second dose, the IFN-γ enzyme-linked immunosorbent spot (ELISPOT) responses were similar for Group: 0+28 and Group: 0+7. Overall, a standard dose of IMVAMUNE (0.5 mL of 1 x 10(8) TCID/mL) administered subcutaneously was safe and well tolerated. A second dose of IMVAMUNE at Day 28 compared to Day 7 provided greater antibody responses and the maximal number of responders. By Day 14 after the second dose, IFN-γ ELISPOT responses were similar for Group: 0+28 and Group: 0
Gibson, Edward; Begum, Najida; Martinón-Torres, Federico; Safadi, Marco Aurélio; Sackeyfio, Alfred; Hackett, Judith; Rajaram, Sankarasubramanian
Influenza poses a significant burden on healthcare systems and society, with under-recognition in the paediatric population. Existing vaccination policies (largely) target the elderly and other risk groups where complications may arise. The goal of this study was to evaluate the cost-effectiveness of annual paediatric vaccination (in 2-17-year-olds) with live attenuated influenza vaccination (LAIV), as well as the protective effect on the wider population in England and Wales (base). The study aimed to demonstrate broad applications of the model in countries where epidemiological and transmission data is limited and that have sophisticated vaccination policies (Brazil, Spain, and Taiwan). The direct and indirect impact of LAIV in the paediatric cohort was simulated using an age-stratified dynamic transmission model over a 5-year time horizon of daily cycles and applying discounting of 3.5% in the base case. Pre-existing immunity structure was based on a 1-year model run. Sensitivity analyses were conducted. In the base case for England and Wales, the annual paediatric strategy with LAIV was associated with improvements in influenza-related events and quality-adjusted life years (QALYs) lost, yielding an incremental cost per QALY of £6,208. The model was robust to change in the key input parameters. The probabilistic analysis demonstrated LAIV to be cost effective in more than 99% of iterations, assuming a willingness-to-pay threshold of £30,000. Incremental costs per QALY for Brazil were £2,817, and for the cases of Spain and Taiwan the proposed strategy was dominant over the current practice. In addition to existing policies, annual paediatric vaccination using LAIV provides a cost-effective strategy that offers direct and indirect protection in the wider community. Paediatric vaccination strategies using LAIV demonstrated clinical and economic benefits over alternative (current vaccination) strategies in England and Wales as well as Brazil, Spain, and Taiwan.
Chen, Chiann-Chyi; Ron, Yacov
Substantial progress in the development of new anti-viral drugs has taken place in recent years. Most of these new drugs belong to three groups of compounds, nucleoside analogs, thymidine kinase-dependent nucleotide analogs and specific viral enzyme inhibitors. Although these drugs revolutionized the treatment of several viral diseases, the involvement of the immune system is crucial for complete recovery and prevention of re-infection. New advances in the understanding of immune regulation mechanisms, mainly the role of cytokines, led to the development of several new immunologically-based anti-viral drugs and treatments. The most studied group of immunomodulators is the cytokines, some of which were shown to act as potent stimulators of immune responses. Other, non-cytokine immune modulators have also been successfully employed in both humans and experimental animals as anti-viral drugs of which several are currently in clinical trials. Advances in genetic engineering and transgenic mouse technologies facilitated the production of humanized as well as authentic human anti-viral monoclonal antibodies. Some of these antibodies proved to be clinically efficacious and are commercially produced as anti-viral drugs. As is often the case in anti-viral treatments, a combination of conventional and an immune-mediated anti-viral drugs or a combination therapy involving immunomodulators, therapeutic vaccines, immune intervention and even gene therapy might prove most efficacious as a treatment for a particular virus. Most of the advances made in anti-viral treatments have also been applied to the development of new vaccines. Some of the classical attenuated viruses are being replaced by recombinant attenuated viruses. Recombinant viral vaccines containing genes encoding other viral antigens and/or cytokines are being tested as new vaccines. Several chimeric viral vaccines have proven efficacious in experimental animals and are now in different phases of clinical trials
Staino, Andrea; Basu, Biswajit
The paper discusses some of the recent developments in vibration control strategies for wind turbines, and in this context proposes a new dual control strategy based on the combination and modification of two recently proposed control schemes. Emerging trends in the vibration control of both onshore and offshore wind turbines are presented. Passive, active and semi-active structural vibration control algorithms have been reviewed. Of the existing controllers, two control schemes, active pitch control and active tendon control, have been discussed in detail. The proposed new control scheme is a merger of active tendon control with passive pitch control, and is designed using a Pareto-optimal problem formulation. This combination of controllers is the cornerstone of a dual strategy with the feature of decoupling vibration control from optimal power control as one of its main advantages, in addition to reducing the burden on the pitch demand. This dual control strategy will bring in major benefits to the design of modern wind turbines and is expected to play a significant role in the advancement of offshore wind turbine technologies. © 2015 The Author(s) Published by the Royal Society. All rights reserved.
Nguyen, Le Thi Cam; Gu, Yongqi
This study investigates the effects of strategy-based instruction (SBI) on the promotion of learner autonomy (LA). LA was conceptualized and operationally defined as learner self-initiation and learner self-regulation. An intervention study was conducted with the participation of 37 students in an experimental group, and 54 students in two control…
Quardokus, Kathleen M.
Numerous reports demand changes in college and university teaching practices. This is especially true for science, technology, engineering and mathematics (STEM) disciplines. STEM stakeholders are concerned about student retention within STEM majors, as well as the lack of sufficient graduates with the knowledge to advance these fields. A common conclusion of these reports is that teaching practices must change. Although these calls for change have occurred for decades, STEM fields have yet to experience widespread change. Thus, there is a need for more effective change strategies. Recently, researchers have suggested that effective change strategies should focus on changing the environments of academic departments. This is in contrast to most commonly-used change strategies that focus on individual instructors. Environmentfocused change strategies have two main varieties: those that have a goal of implementing prescribed outcomes, and those that expect the outcomes to emerge from the change process. Yet, little is known about how to enact environment-focused change strategies. The goal of this research is to provide guidance for change agents and researchers by analyzing a large-scale change initiative from the perspective of two environment-focused change strategies: Kotter's eight-stage leadership process (prescribed) and complexity leadership theory (emergent). This analysis was guided by two research questions. 1. Within the context of a higher education change initiative, how is the change process described from the perspectives of two distinct leadership theories? 2. How do these descriptions frame problems and solutions associated with change? Each change strategy identified different activities as contributing to change as well as different missed opportunities. For example, when the change vision was not communicated effectively, the eight-stage leadership process indicated that the involvement of the department chair was needed, while complexity
Zhang, Lingli; Li, Fei
Obesity has become a worldwide public health concern. In particular, obesity caused by excessive energy intake was widespread which has strong causal relationship with food preference behaviors. In this review, we would briefly talk about characteristics of feeding behaviors inducing obesity, as well as the possible neurophysiological mechanisms involved in food preference formation and development. Meantime, we would introduce some regulation strategies to deal with obesity which mainly based on the current feeding behaviors of the obese.
Full Text Available To balance the contradiction between comprehensiveness of system-of-systems (SoS description and cost of modeling and simulation, a non-uniform hybrid strategy (NUHYS is proposed. NUHYS groups elements of an SoS operation into system community or relatively independent system based on contributors complexity and focus relationship according to the focus of SoS problem. Meanwhile, modeling methods are categorized based on details attention rate and dynamic attention rate, seeking for matching contributors. Taking helicopter rescue in earthquake relief as an example, the procedure of applying NUHYS and its effectiveness are verified.
KITAKAWA, Azumi; 北川, あず美
In recent years, the focus has shifted from the teacher to the learner in foreign/second language education. There are some learner's factors which affect second language learning, for example, intelligence, aptitude, personality, motivation, attitude, preferences, beliefs, age of acquisition, target language, task, environment and in particular, language learning strategies. As one of second language learners, I have been seeking for the better way since I started learning English in my juni...
Monteiro, Mariana P
Obesity is one of the largest and fastest growing public health problems in the world. Last century social changes have set an obesogenic milieu that calls for micro and macro environment interventions for disease prevention, while treatment is mandatory for individuals already obese. The cornerstone of overweight and obesity treatment is diet and physical exercise. However, many patients find lifestyle modifications difficult to comply and prone to failure in the long-term; therefore many patients consider anti-obesity drugs an important adjuvant if not a better alternative to behavioral approach or obesity surgery. Since the pharmacological options for obesity treatment remain quite limited, this is an exciting research area, with new treatment targets and strategies on the horizon. This review discusses the development of innovative therapeutic agents, focusing in energy homeostasis regulation and the use of molecular vaccines, targeting hormones such as somatostatin, GIP and ghrelin, to reduce body weight.
Metcalf, C J E; Tatem, A; Bjornstad, O N; Lessler, J; O'Reilly, K; Takahashi, S; Cutts, F; Grenfell, B T
Measles vaccination is estimated to have averted 13·8 million deaths between 2000 and 2012. Persisting heterogeneity in coverage is a major contributor to continued measles mortality, and a barrier to measles elimination and introduction of rubella-containing vaccine. Our objective is to identify determinants of inequities in coverage, and how vaccine delivery must change to achieve elimination goals, which is a focus of the WHO Decade of Vaccines. We combined estimates of travel time to the nearest urban centre (⩾50 000 people) with vaccination data from Demographic Health Surveys to assess how remoteness affects coverage in 26 African countries. Building on a statistical mapping of coverage against age and geographical isolation, we quantified how modifying the rate and age range of vaccine delivery affects national coverage. Our scenario analysis considers increasing the rate of delivery of routine vaccination, increasing the target age range of routine vaccination, and enhanced delivery to remote areas. Geographical isolation plays a key role in defining vaccine inequity, with greater inequity in countries with lower measles vaccine coverage. Eliminating geographical inequities alone will not achieve thresholds for herd immunity, indicating that changes in delivery rate or age range of routine vaccination will be required. Measles vaccine coverage remains far below targets for herd immunity in many countries on the African continent and is likely to be inadequate for achieving rubella elimination. The impact of strategies such as increasing the upper age range eligible for routine vaccination should be considered.
Wang, Aili; Xiao, Yanni; Cheke, Robert A.
A piece-wise epidemic model of a switching vaccination program, implemented once the number of people exposed to a disease-causing virus reaches a critical level, is proposed. In addition, variation or uncertainties in interventions are examined with a perturbed system version of the model. We also analyzed the global dynamic behaviors of both the original piece-wise system and the perturbed version theoretically, using generalized Jacobian theory, Lyapunov constants for a non-smooth vector f...
Svetlana V Shcherbik
Full Text Available BACKGROUND: Live attenuated influenza vaccine viruses (LAIVs can be generated by classical reassortment of gene segments between a cold adapted, temperature sensitive and attenuated Master Donor Virus (MDV and a seasonal wild-type (wt virus. The vaccine candidates contain hemagglutinin (HA and neuraminidase (NA genes derived from the circulating wt viruses and the remaining six genes derived from the MDV strains. Rapid, efficient selection of the viruses with 6∶2 genome compositions from the large number of genetically different viruses generated during reassortment is essential for the biannual production schedule of vaccine viruses. METHODOLOGY/PRINCIPAL FINDINGS: This manuscript describes a new approach for the genotypic analysis of LAIV reassortant virus clones based on pyrosequencing. LAIV candidate viruses were created by classical reassortment of seasonal influenza A (H3N2 (A/Victoria/361/2011, A/Ohio/02/2012, A/Texas/50/2012 or influenza A (H7N9 (A/Anhui/1/2013 wt viruses with the MDV A/Leningrad/134/17/57(H2N2. Using strain-specific pyrosequencing assays, mixed gene variations were detected in the allantoic progenies during the cloning procedure. The pyrosequencing analysis also allowed for estimation of the relative abundance of segment variants in mixed populations. This semi-quantitative approach was used for selecting specific clones for the subsequent cloning procedures. CONCLUSIONS/SIGNIFICANCE: The present study demonstrates that pyrosequencing analysis is a useful technique for rapid and reliable genotyping of reassortants and intermediate clones during the preparation of LAIV candidates, and can expedite the selection of vaccine virus candidates.
Shukarev, Georgi; Callendret, Benoit; Luhn, Kerstin; Douoguih, Macaya
The consequences of the 2013-16 Ebola Zaire virus disease epidemic in West Africa were grave. The economies, healthcare systems and communities of Guinea, Sierra Leone and Liberia were devastated by over 18 months of active Ebola virus transmission, followed by sporadic resurgences potentially related to sexual transmission by survivors with viral persistence in body fluids following recovery. The need to develop and implement strategies to prevent and mitigate future outbreaks is now beyond dispute. The potential for unpredictable outbreaks of indeterminate duration, and control challenges posed by the possibility of sporadic re-emergence, mean that implementation of an effective vaccination program for outbreak containment necessitates a vaccine providing durable immunity. Heterologous prime-boost vaccine regimens deliver the same or similar antigens through different vaccine types, the first to prime and the second to boost the immune system. Ad26.ZEBOV/MVA-BN-Filo is an investigational Ebola Zaire vaccine regimen that uses this heterologous prime-boost approach. Preliminary Phase 1 data suggest that Ad26.ZEBOV/MVA-BN-Filo confers durable immunity for at least 240 d and is well-tolerated with a good safety profile. This regimen may therefore be suitable for prophylactic use in a regional or targeted population vaccination strategy, and could potentially aid prevention and control of future Ebola outbreaks.
Mazzola, Giovanni; Macaluso, Fabio Salvatore; Adamoli, Lucia; Renna, Sara; Cascio, Antonio; Orlando, Ambrogio
The treatment of inflammatory bowel disease (IBD) has been revolutionized by the use of immunomodulatory agents. Although these potent drugs are effective in controlling disease activity, they also cause an increased risk of new infections or reactivation of latent infections. On these premises, we aimed to provide guidance on the definitions of immunocompromised patients, opportunistic infections and the risk factors associated with their occurrence in an IBD context, and to suggest the proper screening tests for infectious diseases and the vaccination schedules to perform before and/or during therapy with immunomodulators. All the most recent evidences - filtered by the combined work of gastroenterologists and infectious disease experts - were summarized with the aim to provide a practical standpoint for the physician. A systematic screening of all infections which may arise during therapy with immunomodulator drugs is necessary in all patients with IBD. The ideal timing to perform screening tests and vaccinations is at the diagnosis of the disease, regardless of its severity at onset, because the course of IBD and its treatment may vary over time, and an immunocompromised status may hamper efficacy and/or possibility to perform all necessary vaccines. Copyright © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.
Walker, A; Srinivas, G B
Hamsters are routinely infected with virulent Leptospira for two purposes in the regulation of biologics: the performance of Codified potency tests and maintenance of challenge culture for the Codified potency tests. Options for reducing animal use in these processes were explored in a plenary lecture at the "International Workshop on Alternative Methods for Leptospira Vaccine Potency Testing: State of the Science and the Way Forward" held at the Center for Veterinary Biologics in September 2012. The use of validated in vitro potency assays such as those developed by the U.S. Department of Agriculture for Leptospira (L.) canicola, Leptospira grippotyphosa, Leptospira pomona, and Leptospira icterohaemorrhagiae rather than the Codified hamster vaccination-challenge assay was encouraged. Alternatives such as reduced animal numbers in the hamster vaccination-challenge testing were considered for problematic situations. Specifically, the merits of sharing challenge controls, reducing group sizes, and eliminating animals for concurrent challenge dose titration were assessed. Options for maintaining virulent, stable cultures without serial passage through hamsters or with decreased hamster use were also discussed. The maintenance of virulent Leptospira without the use of live animals is especially difficult since a reliable means to maintain virulence after multiple in vitro passages has not yet been identified. Published by Elsevier Ltd.
Full Text Available The purpose of the present study was to investigate the relationship between Iranian EFL learners’ use of vocabulary learning strategies and their autonomy with a focus on the gender. To meet this objective, 82(39 males and 43 females sophomore and junior students majoring in English Language Teaching who had passed at least 45 credits at Tabriz Azad University, in Iran were asked to take part in the study by filling the questionnaires on learner autonomy (LAQ and vocabulary learning strategies (VLSQ. After discarding incomplete questionnaires, 70 acceptable cases were used in the statistical analysis. Correlation analysis indicated a statistically significant and positive relationship between Iranian EFL learners’ use of vocabulary learning strategies and their autonomy for both male and female students. The findings can have some pedagogical implications for teachers.
The article examines some of the strategies employed by the Mexican health authorities that led to the organization of massive and obligatory smallpox vaccination campaigns from the late 1880s to the 1940s, a period of Mexican history that corresponds to the Porfirio Díaz regime (1877-1911), to the armed phase of the Mexican Revolution (1910-1920), and to the first two decades of the Post-revolutionary governments (1920-1940). Attention will be placed of the vaccination programs in the main urban settings, notably in Mexico City, as well as the gradual but decisive organization and regulation of vaccination campaigns in the heterogeneous rural milieu. Furthermore, the importance that hygienic education acquired will be explored, as well as the divergent and contested responses that emerged due to the obligatory vaccination campaigns, responses that included resistance, fear, uncertainty and widespread acceptance.
Full Text Available OBJECTIVE: We performed a qualitative study among women within 5 years of Gestational Diabetes (GDM diagnosis. Our aim was to identify the key elements that would enhance participation in a type 2 diabetes (DM2 prevention program. RESEARCH DESIGN AND METHODS: Potential participants received up to three invitation letters from their GDM physician. Four focus groups were held. Discussants were invited to comment on potential facilitators/barriers to participation and were probed on attitudes towards meal replacement and Internet/social media tools. Recurring themes were identified through qualitative content analysis of discussion transcripts. RESULTS: Among the 1,201 contacted and 79 eligible/interested, 29 women attended a focus group discussion. More than half of discussants were overweight/obese, and less than half were physically active. For DM2 prevention, a strong need for social support to achieve changes in dietary and physical activity habits was expressed. In this regard, face-to-face interactions with peers and professionals were preferred, with adjunctive roles for Internet/social media. Further, direct participation of partners/spouses in a DM2 prevention program was viewed as important to enhance support for behavioural change at home. Discussants highlighted work and child-related responsibilities as potential barriers to participation, and emphasized the importance of childcare support to allow attendance. Meal replacements were viewed with little interest, with concerns that their use would provide a poor example of eating behaviour to children. CONCLUSIONS: Among women within 5 years of a GDM diagnosis who participated in a focus group discussion, participation in a DM2 prevention program would be enhanced by face-to-face interactions with professionals and peers, provision of childcare support, and inclusion of spouses/partners.
Dasgupta, Kaberi; Da Costa, Deborah; Pillay, Sabrina; De Civita, Mirella; Gougeon, Réjeanne; Leong, Aaron; Bacon, Simon; Stotland, Stephen; Chetty, V Tony; Garfield, Natasha; Majdan, Agnieszka; Meltzer, Sara
We performed a qualitative study among women within 5 years of Gestational Diabetes (GDM) diagnosis. Our aim was to identify the key elements that would enhance participation in a type 2 diabetes (DM2) prevention program. Potential participants received up to three invitation letters from their GDM physician. Four focus groups were held. Discussants were invited to comment on potential facilitators/barriers to participation and were probed on attitudes towards meal replacement and Internet/social media tools. Recurring themes were identified through qualitative content analysis of discussion transcripts. Among the 1,201 contacted and 79 eligible/interested, 29 women attended a focus group discussion. More than half of discussants were overweight/obese, and less than half were physically active. For DM2 prevention, a strong need for social support to achieve changes in dietary and physical activity habits was expressed. In this regard, face-to-face interactions with peers and professionals were preferred, with adjunctive roles for Internet/social media. Further, direct participation of partners/spouses in a DM2 prevention program was viewed as important to enhance support for behavioural change at home. Discussants highlighted work and child-related responsibilities as potential barriers to participation, and emphasized the importance of childcare support to allow attendance. Meal replacements were viewed with little interest, with concerns that their use would provide a poor example of eating behaviour to children. Among women within 5 years of a GDM diagnosis who participated in a focus group discussion, participation in a DM2 prevention program would be enhanced by face-to-face interactions with professionals and peers, provision of childcare support, and inclusion of spouses/partners.
Zambach, Sine; Holst, Philip; Francker, Zenia Worm
climate friendly events into the business processes, particularly for large-scale companies. The value of such a module or integration has many dimensions. It creates a green CSR-profile within the core business of the ERP-producer, who has a potential marketing focus. An environmental ERP......-module will additionally create financial and social value to the company that utilizes ERP which will retain for example optimization of logistics and a decrease of CO2 emission. Finally, a legal regulation in 2009 requires the 1000 largest companies in Denmark to inform about their CSR-activities, which could...
Full Text Available Abstract Background Intermittent preventive treatment of malaria in infants (IPTi using sulphadoxine-pyrimethamine and linked to the expanded programme on immunization (EPI is a promising strategy for malaria control in young children. As evidence grows on the efficacy of IPTi as public health strategy, information is needed so that this novel control tool can be put into practice promptly, once a policy recommendation is made to implement it. This paper describes the development of a behaviour change communication strategy to support implementation of IPTi by the routine health services in southern Tanzania, in the context of a five-year research programme evaluating the community effectiveness of IPTi. Methods Mixed methods including a rapid qualitative assessment and quantitative health facility survey were used to investigate communities' and providers' knowledge and practices relating to malaria, EPI, sulphadoxine-pyrimethamine and existing health posters. Results were applied to develop an appropriate behaviour change communication strategy for IPTi involving personal communication between mothers and health staff, supported by a brand name and two posters. Results Malaria in young children was considered to be a nuisance because it causes sleepless nights. Vaccination services were well accepted and their use was considered the mother's responsibility. Babies were generally taken for vaccination despite complaints about fevers and swellings after the injections. Sulphadoxine-pyrimethamine was widely used for malaria treatment and intermittent preventive treatment of malaria in pregnancy, despite widespread rumours of adverse reactions based on hearsay and newspaper reports. Almost all health providers said that they or their spouse were ready to take SP in pregnancy (96%, 223/242. A brand name, key messages and images were developed and pre-tested as behaviour change communication materials. The posters contained public health messages
Mushi, Adiel K; Schellenberg, Joanna; Mrisho, Mwifadhi; Manzi, Fatuma; Mbuya, Conrad; Mponda, Haji; Mshinda, Hassan; Tanner, Marcel; Alonso, Pedro; Pool, Robert; Schellenberg, David
Intermittent preventive treatment of malaria in infants (IPTi) using sulphadoxine-pyrimethamine and linked to the expanded programme on immunization (EPI) is a promising strategy for malaria control in young children. As evidence grows on the efficacy of IPTi as public health strategy, information is needed so that this novel control tool can be put into practice promptly, once a policy recommendation is made to implement it. This paper describes the development of a behaviour change communication strategy to support implementation of IPTi by the routine health services in southern Tanzania, in the context of a five-year research programme evaluating the community effectiveness of IPTi. Mixed methods including a rapid qualitative assessment and quantitative health facility survey were used to investigate communities' and providers' knowledge and practices relating to malaria, EPI, sulphadoxine-pyrimethamine and existing health posters. Results were applied to develop an appropriate behaviour change communication strategy for IPTi involving personal communication between mothers and health staff, supported by a brand name and two posters. Malaria in young children was considered to be a nuisance because it causes sleepless nights. Vaccination services were well accepted and their use was considered the mother's responsibility. Babies were generally taken for vaccination despite complaints about fevers and swellings after the injections. Sulphadoxine-pyrimethamine was widely used for malaria treatment and intermittent preventive treatment of malaria in pregnancy, despite widespread rumours of adverse reactions based on hearsay and newspaper reports. Almost all health providers said that they or their spouse were ready to take SP in pregnancy (96%, 223/242). A brand name, key messages and images were developed and pre-tested as behaviour change communication materials. The posters contained public health messages, which explained the intervention itself, how and when
Cynthia A. Blum
Full Text Available While preceptors are a vital link in student nurse practice education, ongoing support beyond an initial orientation is often lacking. It has been reported in the literature that preceptors experience stress related to difficulties in handling preceptee situations. They are frustrated by negative experiences centered on preceptor-identified hallmarks of unsafe practice including the inability to demonstrate knowledge and skills; attitude problems; unprofessional behavior; and poor communication skills. Their unrealized expectations for novices threaten their commitment to their preceptor role. As part of a larger study testing the effectiveness of podcasts as an ongoing method of preceptor support, this paper addresses the developmental stage of the podcasts. A team of academic and acute care nurse educators developed scripts for eventual filming of four podcasts focusing on unsafe practice issues, designed to provide continual support through web-based availability. The use of podcast technology is consistent with the learning styles of digital natives and is a demonstrated and valuable educational resource to review, reinforce, and clarify difficult concepts. These podcasts were informed through preceptor focus groups to address situational and environmental realism for student behaviors and preceptor responses.
DeLorme, D.; Hagen, S. C.; Stephens, S. H.
This presentation reports results of focus groups with coastal resource managers on suggestions for effectively sharing sea level rise (SLR) scientific research with the public and other target audiences. The focus groups were conducted during three annual stakeholder workshops as an important and innovative component of an ongoing five-year multi-disciplinary NOAA-funded project, Ecological Effects of Sea Level Rise in the Northern Gulf of Mexico (EESLR-NGOM). The EESLR-NGOM project is assessing SLR risks to the natural and built environment along the Mississippi, Alabama, and Florida Panhandle coasts. The purpose was to engage stakeholders (e.g., coastal resource managers) in helping target, translate, and tailor the EESLR-NGOM project's scientific findings and emerging products so they are readily accessible, understandable, and useful. The focus groups provided insight into stakeholders' SLR informational and operational needs, solicited input on the project's products, and gathered suggestions for public communication and outreach. A total of three ninety-minute focus groups of between eight and thirteen participants each were conducted at annual workshops in Alabama, Florida, and Mississippi. The moderator asked a series of open-ended questions about SLR-related topics using an interview guide and encouraged participant interaction. All focus group audio-recordings were transcribed, and analyzed by carefully reading the 102 total pages of transcript data and identifying patterns and themes. Participants thought outreach about SLR impact and the EESLR-NGOM project scientific research/products was vital and acknowledged various communication challenges and opportunities. They identified three target audiences (local officials, general public, coastal resource managers themselves) that likely require different educational efforts and tools. Participants felt confident the EESLR-NGOM project products will benefit their resource planning and decision making and
Full Text Available The development of vaccines to treat and prevent human immunodeficiency virus (HIV infection has been hampered by an incomplete understanding of “protective” immune responses against HIV. Natural control of HIV-1 infection is associated with T-cell responses against HIV-1 Gag proteins, particularly CD8+ T-cell responses restricted by “protective” HLA-B alleles, but other immune responses also contribute to immune control. These immune responses appear to include IgG antibodies to HIV-1 Gag proteins, interferon-a-dependant natural killer (NK cell responses and plasmacytoid dendritic cell (pDC responses. Here, it is proposed that isotype diversification of IgG antibodies against HIV-1 Gag proteins, to include IgG2, as well as IgG3 and IgG1 antibodies, will broaden the function of the antibody response and facilitate accessory cell responses against HIV-1 by NK cells and pDCs. We suggest that this should be investigated as a vaccination strategy for HIV-1 infection.
Adoption of new vaccines in developing countries is critical to reducing child mortality and meeting Millennium Development Goal 4. However, such introduction has historically suffered from significant delays that can be attributed to various factors including (i) lack of recognition of the value of a vaccine, (ii) factors related to weak health systems, and (iii) policy considerations. Recently, the Global Alliance for Vaccines and Immunization (GAVI) supported efforts to accelerate the introduction of Haemophilus influenzae type b (Hib) vaccines in developing countries, which resulted in a significant surge in vaccine adoption by these countries. The experience with Hib vaccines, as well as similar efforts by GAVI to support the introduction of new pneumococcal and rotavirus vaccines, provides a strategy for new vaccine adoption that is reviewed in this paper, providing a useful model to help accelerate the uptake of other life-saving vaccines. This strategy addresses barriers for vaccine adoption by focusing on three major areas: (i) communications to increase awareness about the various factors needed for evidence-based decisions that meet a country's health goals; (ii) research activities to answer key questions that support vaccine introduction and long-term programme sustainability; and (iii) coordination with the various stakeholders at global, regional and country levels to ensure successful programme implementation.
Full Text Available This paper aims at outlining a successful implementation of a project within LEADER framework, which is a local development method which allows local actors to develop an area by using its endogenous development potential. After a brief presentation of the characteristics of regional development strategies in Romania, there were emphasized the objectives and activities encompassed in a local development plan, managed by the leaders of the local action group called ‘Vrancea County’. In order to reinforce the strengths of Vrancea County and implicitly to assure a sustainable development of this area from the South-East part of Romania, a LAG constituted through a partnership between public and private actors settled a set of priorities to be exploited by means of specific actions. The goal of this paper is to highlight these priorities, by integrating them in a project management approach. The paper concludes with specifications about how Microsoft Project software could support project management initiatives that will be developed by the LAG Vrancea County in the next period.
Richer, Luciana Meirelles; Brisson, Dustin; Melo, Rita; Ostfeld, Richard S; Zeidner, Nordin; Gomes-Solecki, Maria
A high prevalence of infection with Borrelia burgdorferi in ixodid ticks is correlated with a high incidence of Lyme disease. The transmission of B. burgdorferi to humans can be disrupted by targeting 2 key elements in its enzootic cycle: the reservoir host and the tick vector. In a prospective 5-year field trial, we show that oral vaccination of wild white-footed mice resulted in outer surface protein A-specific seropositivity that led to reductions of 23% and 76% in the nymphal infection prevalence in a cumulative, time-dependent manner (2 and 5 years, respectively), whereas the proportion of infected ticks recovered from control plots varied randomly over time. Significant decreases in tick infection prevalence were observed within 3 years of vaccine deployment. Implementation of such a long-term public health measure could substantially reduce the risk of human exposure to Lyme disease. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: firstname.lastname@example.org.
: The use of specific immunotherapy (SIT) for allergic disorders has recently been extended by introduction of a convenient, tablet-based, disease-modifying vaccine against grass pollen allergy. Allergy immunotherapy tablet (AIT) programmes targeting house dust mite and other allergies are currently in late-phase development. Next-generation allergy vaccines can have optimised potency and onset of action without compromising safety or convenience. Key to achieving these objectives is a combination of evidence-based mode-of-action studies and biomarker-centric translational research approaches. This will rely on using biobank and bioinformatics resources for multi-omic characterisations of the 'immunome' of allergic disease. Other important areas are ongoing paediatric trials and long-term studies in adults for further defining the potential role of SIT in allergic disease and primary prevention of asthma. Finally, combining cellular- and serological-based assays, and developments in targeted delivery platforms and component-resolved diagnostics will lead to increased ability to stratify patients, with more personalised diagnosis and treatment. © 2011 John Wiley & Sons A/S.
Jit, Mark; Choi, Yoon Hong; Laprise, Jean-François; Boily, Marie-Claude; Drolet, Mélanie; Brisson, Marc
Two-dose human papillomavirus (HPV) vaccine schedules may provide short-term protection but their long-term population impact is unknown. Two models of HPV transmission and associated cervical disease (squamous and glandular, neoplasia and cancer) were fitted to data from England and Canada on HPV epidemiology, sexual behaviour, cervical screening outcomes and cervical cancer incidence. Models suggest that at 40-80% coverage, if two-dose schedules protect vaccinees for 20 years, then the benefits of the third dose are small. If two doses protect for 10 years, then the third dose may prevent as many cancers as the first two. At 80% coverage, numbers needed to receive a third dose to prevent an additional cancer are 5900-110,000 (England), 3000-5100 (Canada) with 20 years two-dose protection, and 2000-5300 (England), 760-950 (Canada) with 10 years two-dose protection. Results enable decision makers to quantify risks associated with two-dose schedules despite remaining uncertainties in vaccine duration and cross-protection. Copyright © 2014 Elsevier Ltd. All rights reserved.
Full Text Available One of the potential threats to public health microbiology in 21st century is the increased mortality rate caused by Zika virus (ZIKV, a mosquito-borne flavivirus. The severity of ZIKV infection urged World Health Organization (WHO to declare this virus as a global concern. The limited knowledge on the structure, virulent factors, and replication mechanism of the virus posed as hindrance for vaccine development. Several vector and non-vector-borne mode of transmission are observed for spreading the disease. The similarities of the virus with other flaviviruses such as dengue and West Nile virus are worrisome; hence, there is high scope to undertake ZIKV research that probably provide insight for novel therapeutic intervention. Thus, this review focuses on the recent aspect of ZIKV research which includes the outbreak, genome structure, multiplication and propagation of the virus, current animal models, clinical manifestations, available treatment options (probable vaccines and therapeutics, and the recent advancements in computational drug discovery pipelines, challenges and limitation to undertake ZIKV research. The review suggests that the infection due to ZIKV became one of the universal concerns and an interdisciplinary environment of in vitro cellular assays, genomics, proteomics, and computational biology approaches probably contribute insights for screening of novel molecular targets for drug design. The review tried to provide cutting edge knowledge in ZIKV research with future insights required for the development of novel therapeutic remedies to curtail ZIKV infection.
Shankar, Apoorva; Patil, Amulya A.; Skariyachan, Sinosh
One of the potential threats to public health microbiology in 21st century is the increased mortality rate caused by Zika virus (ZIKV), a mosquito-borne flavivirus. The severity of ZIKV infection urged World Health Organization (WHO) to declare this virus as a global concern. The limited knowledge on the structure, virulent factors, and replication mechanism of the virus posed as hindrance for vaccine development. Several vector and non-vector-borne mode of transmission are observed for spreading the disease. The similarities of the virus with other flaviviruses such as dengue and West Nile virus are worrisome; hence, there is high scope to undertake ZIKV research that probably provide insight for novel therapeutic intervention. Thus, this review focuses on the recent aspect of ZIKV research which includes the outbreak, genome structure, multiplication and propagation of the virus, current animal models, clinical manifestations, available treatment options (probable vaccines and therapeutics), and the recent advancements in computational drug discovery pipelines, challenges and limitation to undertake ZIKV research. The review suggests that the infection due to ZIKV became one of the universal concerns and an interdisciplinary environment of in vitro cellular assays, genomics, proteomics, and computational biology approaches probably contribute insights for screening of novel molecular targets for drug design. The review tried to provide cutting edge knowledge in ZIKV research with future insights required for the development of novel therapeutic remedies to curtail ZIKV infection. PMID:28959246
Wagemakers, A; Mason, L M K; Oei, A; de Wever, B; van der Poll, T; Bins, A D; Hovius, J W R
Borrelia afzelii is the predominant Borrelia species causing Lyme borreliosis in Europe. Currently there is no human vaccine against Lyme borreliosis, and most research focuses on recombinant protein vaccines against Borrelia burgdorferi sensu stricto. DNA tattooing is a novel vaccination method that can be applied in a rapid vaccination schedule. We vaccinated C3H/HeN mice with B. afzelii strain PKo OspC (outer-surface protein C) using a codon-optimized DNA vaccine tattoo and compared this with recombinant protein vaccination in a 0-2-4 week vaccination schedule. We also assessed protection by DNA tattoo in a 0-3-6 day schedule. DNA tattoo and recombinant OspC vaccination induced comparable total IgG responses, with a lower IgG1/IgG2a ratio after DNA tattoo. Two weeks after syringe-challenge with 5 × 10(5) B. afzelii spirochetes most vaccinated mice had negative B. afzelii tissue DNA loads and all were culture negative. Furthermore, DNA tattoo vaccination in a 0-3-6 day regimen also resulted in negative Borrelia loads and cultures after challenge. To conclude, DNA vaccination by tattoo was fully protective against B. afzelii challenge in mice in a rapid vaccination protocol, and induces a favorable humoral immunity compared to recombinant protein vaccination. Rapid DNA tattoo is a promising vaccination strategy against spirochetes.
Shirley, Rebekah Grace
This dissertation focuses on an integration of energy modeling tools to explore energy transition pathways for emerging economies. The spate of growth in the global South has led to a global energy transition, evidenced in part by a surge in the development of large scale energy infrastructure projects for the provision of reliable electricity service. The rational of energy security and exigency often usher these large scale projects through to implementation with minimal analysis of costs: social and environmental impact, ecological risk, or opportunity costs of alternative energy transition pathways foregone. Furthermore, development of energy infrastructure is inherently characterized by the involvement of a number of state and non-state actors, with varying interests, objectives and access to authority. Being woven through and into social institutions necessarily impacts the design, control and functionality of infrastructure. In this dissertation I therefore conceptualize energy infrastructure as lying at the intersection, or nexus, of people, the environment and energy security. I argue that energy infrastructure plans and policy should, and can, be informed by each of these fields of influence in order to appropriately satisfy local development needs. This case study explores the socio-techno-environmental context of contemporary mega-dam development in northern Borneo. I describe the key actors of an ongoing mega-dam debate and the constellation of their interaction. This highlights the role that information may play in public discourse and lends insight into how inertia in the established system may stymie technological evolution. I then use a combination of power system simulation, ecological modeling and spatial analysis to analyze the potential for, and costs and tradeoffs of, future energy scenarios. In this way I demonstrate reproducible methods that can support energy infrastructure decision making by directly addressing data limitation barriers. I
Jiang, Xi; Liu, Yang; Tan, Ming
The success of the two rotavirus (RV) vaccines (Rotarix and RotaTeq) in many countries endorses a live attenuated vaccine approach against RVs. However, the lower efficacies of both vaccines in many low- and middle-income countries indicate a need to improve the current RV vaccines. The recent discovery that RVs recognize histo-blood group antigens (HBGAs) as potential receptors has significantly advanced our understanding of RV diversity, evolution and epidemiology, providing important new insights into the performances of current RV vaccines in different populations and emphasizing a P-type-based vaccine approach. New understanding of RV diversity and evolution also raises a fundamental question about the 'Jennerian' approach, which needs to be addressed for future development of live attenuated RV vaccines. Alternative approaches to develop safer and more cost-effective subunit vaccines against RVs are also discussed.
.... A potent and effective anti-caries vaccine has long been expected for caries prevention but no vaccines have been brought to market till now mainly due to the low ability to induce and maintain...
Jennings, Lance C
This article provides an overview of some aspects of seasonal, pre-pandemic and pandemic influenza vaccines and initiatives aimed to increase influenza vaccine use within the Asia-Pacific region. Expanding the use of influenza vaccines in the Asia-Pacific region faces many challenges. Despite the recent regional history for the emergence of novel viruses, SARS, the H5N1 and H7N9, and the generation of and global seeding of seasonal influenza viruses and initiatives by WHO and other organisations to expand influenza awareness, the use of seasonal influenza vaccines remains low. The improvement in current vaccine technologies with the licensing of quadrivalent, live-attenuated, cell culture-based, adjuvanted and the first recombinant influenza vaccine is an important step. The development of novel influenza vaccines able to provide improved protection and with improved manufacturing capacity is also advancing rapidly. However, of ongoing concern are seasonal influenza impact and the low use of seasonal influenza vaccines in the Asia-Pacific region. Improved influenza control strategies and their implementation in the region are needed. Initiatives by the World Health Organization (WHO), and specifically the Western Pacific Regional Office of WHO, are focusing on consistent vaccine policies and guidelines in countries in the region. The Asian-Pacific Alliance for the Control of Influenza (APACI) is contributing through the coordination of influenza advocacy initiates. © 2013 Blackwell Publishing Ltd.
Chettri, Jiwan Kumar
significant losses in aquacultural enterprises but vaccination methods implemented since the 1990s have demonstrated their role as one of the most efficient disease control strategies. These have been particularly successful with regard to bacterial diseases in Norwegian salmon farming where multivalent...... vaccines have reduced the need for usage of antibiotics with more than 99 % since the 1980s. Fish can be vaccinated by three different administration routes: injection, immersion and oral vaccination. Injection vaccination (intraperitoneal injection of vaccine) is the most time consuming and labor...... intensive method, which however, provides the best protection of the fish. Immersion vaccination is used for immunization of a high number of small fish is cost-efficient and fast (30 sec immersion into vaccine). Oral vaccination (vaccine in feed) is the least efficient. As in higher vertebrates fish...
Jackson, Ronald J; Worley, Matthew; Trivedi, Shubhanshi; Ranasinghe, Charani
We have established that the efficacy of a heterologous poxvirus vectored HIV vaccine, fowlpox virus (FPV)-HIV gag/pol prime followed by attenuated vaccinia virus (VV)-HIV gag/pol booster immunisation, is strongly influenced by the cytokine milieu at the priming vaccination site, with endogenous IL-13 detrimental to the quality of the HIV specific CD8+ T cell response induced. We have now developed a novel HIV vaccine that co-expresses a C-terminal deletion mutant of the mouse IL-4, deleted for the essential tyrosine (Y119) required for signalling. In our vaccine system, the mutant IL-4C118 can bind to IL-4 type I and II receptors with high affinity, and transiently prevent the signalling of both IL-4 and IL-13 at the vaccination site. When this IL-4C118 adjuvanted vaccine was used in an intranasal rFPV/intramuscular rVV prime-boost immunisation strategy, greatly enhanced mucosal/systemic HIV specific CD8+ T cells with higher functional avidity, expressing IFN-γ, TNF-α and IL-2 and greater protective efficacy were detected. Surprisingly, the IL-4C118 adjuvanted vaccines also induced robust long-lived HIV gag-specific serum antibody responses, specifically IgG1 and IgG2a. The p55-gag IgG2a responses induced were of a higher magnitude relative to the IL-13Rα2 adjuvant vaccine. More interestingly, our recently tested IL-13Rα2 adjuvanted vaccine which only inhibited IL-13 activity, even though induced excellent high avidity HIV-specific CD8+ T cells, had a detrimental impact on the induction of gag-specific IgG2a antibody immunity. Our observations suggest that (i) IL-4 cell-signalling in the absence of IL-13 retarded gag-specific antibody isotype class switching, or (ii) IL-13Rα2 signalling was involved in inducing good gag-specific B cell immunity. Thus, we believe our novel IL-4R antagonist adjuvant strategy offers great promise not only for HIV-1 vaccines, but also against a range of chronic infections where sustained high quality mucosal and systemic T and B
Karademas, Evangelos C; Tsalikou, Calliope; Tallarou, Maria-Christina
In this study we examined whether emotion regulation and illness-focused coping strategies mediate and/ or moderate the relation of illness-related negative emotions to patients' subjective health. One hundred and thirty-five cardiac patients participated in the study. Illness-focused coping strategies were found to mediate the relation of emotions to physical functioning, whereas emotion regulation strategies mediated the relation to psychological well-being. Moreover, an emotion regulation strategy (i.e. emotion suppression) and two illness-focused coping strategies (instrumental coping and adherence) moderated the two relationships. These findings suggest that both emotion regulation and illness-focused coping strategies are integral parts of the illness-related negative emotions-health relationship.
Full Text Available In this study, we evaluated the long-term efficacy of a two-component subunit vaccine against Trypanosoma cruzi infection. C57BL/6 mice were immunized with TcG2/TcG4 vaccine delivered by a DNA-prime/Protein-boost (D/P approach and challenged with T. cruzi at 120 or 180 days post-vaccination (dpv. We examined whether vaccine-primed T cell immunity was capable of rapid expansion and intercepting the infecting T. cruzi. Our data showed that D/P vaccine elicited CD4+ (30-38% and CD8+ (22-42% T cells maintained an effector phenotype up to 180 dpv, and were capable of responding to antigenic stimulus or challenge infection by a rapid expansion (CD8>CD4 with type 1 cytokine (IFNγ+ and TFNα+ production and cytolytic T lymphocyte (CTL activity. Subsequently, challenge infection at 120 or 180 dpv, resulted in 2-3-fold lower parasite burden in vaccinated mice than was noted in unvaccinated/infected mice. Co-delivery of IL-12- and GMCSF-encoding expression plasmids provided no significant benefits in enhancing the anti-parasite efficacy of the vaccine-induced T cell immunity. Booster immunization (bi with recombinant TcG2/TcG4 proteins 3-months after primary vaccine enhanced the protective efficacy, evidenced by an enhanced expansion (1.2-2.8-fold increase of parasite-specific, type 1 CD4+ and CD8+ T cells and a potent CTL response capable of providing significantly improved (3-4.5-fold control of infecting T. cruzi. Further, CD8+T cells in vaccinated/bi mice were predominantly of central memory phenotype, and capable of responding to challenge infection 4-6-months post bi by a rapid expansion to a poly-functional effector phenotype, and providing a 1.5-2.3-fold reduction in tissue parasite replication. We conclude that the TcG2/TcG4 D/P vaccine provided long-term anti-T. cruzi T cell immunity, and bi would be an effective strategy to maintain or enhance the vaccine-induced protective immunity against T. cruzi infection and Chagas disease.
The situation of viral vaccines used in Asian countries is reviewed, focusing on the following vaccines: smallpox, rabies, polio, measles, rubella, mumps, influenza, Japanese encephalitis, hepatitis B, varicella, dengue, and rotavirus. Vaccinations are among the most important strategies to combat communicable diseases caused by bacteria, fungi, parasites, and viruses. Active immunizations are more preferable in most instances than passive ones. It has taken almost 2 centuries to eradicate the highly contagious infection of smallpox from the world. In 1979 the World Health Organization (WHO) announced the global eradication of smallpox. Smallpox vaccination was 1st practiced in 1840 by Dr. Dan Beach Bradley, with the last 2 cases of smallpox reported in Thailand in 1962. Despite the achievement for many years of more ideal rabies vaccine, Semple vaccine continues to be used in developing countries. Attempts should be intensified to produce newer tissue culture vaccines in developing countries themselves and to eradicate vectors. Instances of poliomyelitis were reported in Indonesia, the Philippines, Sri Lanka, India, and Thailand as late as 1983-84, but only a few sporadic cases have occurred in Malaysia since 1980. This mixed record results from polio vaccine having been incorporated into national Expanded Program on Immunization (EPI) programs in many countries. Measles remains 1 of the most common viral infections in children in most developing nations, but morbidity and mortality rates are not accurately obtainable in these countries. Rubella outbreaks have been reported from many countries in Southeast Asia with congenital rubella syndromes due to maternal rubella on the increase in many countries, including Thailand. Children who receive the mumps vaccination are those receiving the combined MMR vaccines. Monovalent mumps vaccine is not obtainable in developing countries. Influenza vaccine is impracticable in most developing countries. Japanese encephalitis
Cottingham, Matthew G; van Maurik, Andre; Zago, Manola; Newton, Angela T.; Richard J Anderson; Howard, M. Keith; Schneider, Jörg; Skinner, Michael A.
The FP9 strain of Fowlpox virus has been described as a more immunogenic recombinant vaccine vector than the Webster FPV-M (FPW) strain (R. J. Anderson et al., J. Immunol. 172:3094-3100, 2004). This study expands the comparison to include two separate recombinant antigens and multiple, rather than single, independent viral clones derived from the two strains. Dual-poxvirus heterologous prime-boost vaccination regimens using individual clones of recombinant FP9 or FPW in combination with recom...
Ganczak, Maria; Gil, Karolina; Korzeń, Marcin; Bażydło, Marta
The seasonal influenza vaccination uptake of the elderly in Poland is one of the lowest in Europe. Objective: to assess the vaccination coverage and influencing determinants in patients ≥65 years of age. A cross-sectional study was conducted (November 2015-April 2016) among consecutive patients admitted to a municipal hospital located in the city of Szczecin, North-west Poland. Patients completed researcher-administered, anonymous questionnaires on socio- demographic data/factors related to the vaccination. Results: The response rate: 92.0%. Among 230 patients (79.6% women, median of age 69 years, range 65-89) who agreed to participate, 34.8% (95% Confidence Interval: 28.6-41.0%) were vaccinated. About 15.7% of respondents had not previously heard about the vaccination; 41.3% of those who stated they were vaccinated or planned on being vaccinated the following year, compared to 19.3% of respondents who stated they were not currently vaccinated (p vaccinated family member (OR = 3.57), and being informed about vaccination (OR = 5.00) were each associated with greater odds of being immunized. Willingness for vaccination the next year was strongly associated (OR = 8.59) with vaccination status. Conclusions: The influenza vaccination uptake in the elderly population in Poland is disturbingly low. Improved education strategies are needed to increase the uptake. Vaccinated respondents are more likely to plan on being vaccinated the following year. Future interventions related to maximizing vaccination coverage should be more tailored, focusing especially on older patients living in rural areas.
Kreutzfeld, Oriana; Müller, Katja; Matuschewski, Kai
Continuous stage conversion and swift changes in the antigenic repertoire in response to acquired immunity are hallmarks of complex eukaryotic pathogens, including Plasmodium species, the causative agents of malaria. Efficient elimination of Plasmodium liver stages prior to blood infection is one of the most promising malaria vaccine strategies. Here, we describe different genetically arrested parasites (GAPs) that have been engineered in Plasmodium berghei, P. yoelii and P. falciparum and compare their vaccine potential. A better understanding of the immunological mechanisms of prime and boost by arrested sporozoites and experimental strategies to enhance vaccine efficacy by further engineering existing GAPs into a more immunogenic form hold promise for continuous improvements of GAP-based vaccines. A critical hurdle for vaccines that elicit long-lasting protection against malaria, such as GAPs, is safety and efficacy in vulnerable populations. Vaccine research should focus on solutions toward turning malaria into a vaccine-preventable disease, which would offer an exciting new path of malaria control.
Full Text Available The complexity of influenza seasonal patterns in the inter-tropical zone impedes the establishment of effective routine immunization programs. China is a climatologically and economically diverse country, which has yet to establish a national influenza vaccination program. Here we characterize the diversity of influenza seasonality in China and make recommendations to guide future vaccination programs.We compiled weekly reports of laboratory-confirmed influenza A and B infections from sentinel hospitals in cities representing 30 Chinese provinces, 2005-2011, and data on population demographics, mobility patterns, socio-economic, and climate factors. We applied linear regression models with harmonic terms to estimate influenza seasonal characteristics, including the amplitude of annual and semi-annual periodicities, their ratio, and peak timing. Hierarchical Bayesian modeling and hierarchical clustering were used to identify predictors of influenza seasonal characteristics and define epidemiologically-relevant regions. The annual periodicity of influenza A epidemics increased with latitude (mean amplitude of annual cycle standardized by mean incidence, 140% [95% CI 128%-151%] in the north versus 37% [95% CI 27%-47%] in the south, p0.6 in provinces located within 27.4°N-31.3°N, slope of latitudinal gradient with latitude -0.016 [95% CI -0.025 to -0.008], p<0.001. In contrast, influenza B activity predominated in colder months throughout most of China. Climate factors were the strongest predictors of influenza seasonality, including minimum temperature, hours of sunshine, and maximum rainfall. Our main study limitations include a short surveillance period and sparse influenza sampling in some of the southern provinces.Regional-specific influenza vaccination strategies would be optimal in China; in particular, annual campaigns should be initiated 4-6 months apart in Northern and Southern China. Influenza surveillance should be strengthened in mid
Full Text Available Vaccinating a buffer of individuals around a case (ring vaccination has the potential to target those who are at highest risk of infection, reducing the number of doses needed to control a disease. We explored the potential vaccine effectiveness (VE of oral cholera vaccines (OCVs for such a strategy.This analysis uses existing data from a cluster-randomized clinical trial in which OCV or placebo was given to 71,900 participants in Kolkata, India, from 27 July to 10 September 2006. Cholera surveillance was then conducted on 144,106 individuals living in the study area, including trial participants, for 5 y following vaccination. First, we explored the risk of cholera among contacts of cholera patients, and, second, we measured VE among individuals living within 25 m of cholera cases between 8 and 28 d after onset of the index case. For the first analysis, individuals living around each index case identified during the 5-y period were assembled using a ring to define cohorts of individuals exposed to cholera index cases. An index control without cholera was randomly selected for each index case from the same population, matched by age group, and individuals living around each index control were assembled using a ring to define cohorts not exposed to cholera cases. Cholera attack rates among the exposed and non-exposed cohorts were compared using different distances from the index case/control to define the rings and different time frames to define the period at risk. For the VE analysis, the exposed cohorts were further stratified according to the level of vaccine coverage into high and low coverage strata. Overall VE was assessed by comparing the attack rates between high and low vaccine coverage strata irrespective of individuals' vaccination status, and indirect VE was assessed by comparing the attack rates among unvaccinated members between high and low vaccine coverage strata. Cholera risk among the cohort exposed to cholera cases was 5
Raymond, Donald D.; Bajic, Goran; Ferdman, Jack; Suphaphiphat, Pirada; Settembre, Ethan C.; Moody, M. Anthony; Schmidt, Aaron G.; Harrison, Stephen C. (Duke-MED); (CH-Boston); (Seqirus)
Antigenic variation requires frequent revision of annual influenza vaccines. Next-generation vaccine design strategies aim to elicit a broader immunity by directing the human immune response toward conserved sites on the principal viral surface protein, the hemagglutinin (HA). We describe a group of antibodies that recognize a hitherto unappreciated, conserved site on the HA of H1 subtype influenza viruses. Mutations in that site, which required a change in the H1 component of the 2017 vaccine, had not previously “taken over” among circulating H1 viruses. Our results encourage vaccine design strategies that resurface a protein to focus the immune response on a specific region.
Kotloff, KL; Winickoff, JP; Ivanoff, B; Clemens, JD; Swerdlow, DL; Sansonetti, PJ; Adak, GK; Levine, MM
Few studies provide data on the global morbidity and mortality caused by infection with Shigella spp.; such estimates are needed, however, to plan strategies of prevention and treatment. Here we report the results of a review of the literature published between 1966 and 1997 on Shigella infection.
Hogue, Michael D; Meador, Anna E
Vaccines are among most cost-effective public health strategies. Despite effective vaccines for many bacterial and viral illnesses, tens of thousands of adults and hundreds of children die each year in the United States from vaccine-preventable diseases. Underutilization of vaccines requires rethinking the approach to incorporating vaccines into practice. Arguably, immunizations could be a part all health care encounters. Shared responsibility is paramount if deaths are to be reduced. This article reviews the available vaccines in the US market, as well as practice recommendations of the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices. Copyright © 2016 Elsevier Inc. All rights reserved.
Riphagen-Dalhuisen, Josien; Frijstein, Gerard; van der Geest-Blankert, Nannet; Danhof-Pont, Marita; de Jager, Herbert; Bos, Nita; Smeets, Ed; de Vries, Marjan; Gallee, Pieter; Hak, Eelko
Influenza transmitted by health care workers (HCWs) is a potential threat to frail patients in acute health care settings. Therefore, immunizing HCWs against influenza should receive high priority. Despite recommendations of the World Health Organization, vaccine coverage of HCWs remains low in all European countries. This study explores the use of intervention strategies and methods to improve influenza vaccination rates among HCWs in an acute care setting. The Intervention Mapping (IM) method was used to systematically develop and implement an intervention strategy aimed at changing influenza vaccination behaviour among HCWs in Dutch University Medical Centres (UMCs). Carried out during the influenza seasons 2009/2010 and 2010/2011, the interventions were then qualitatively and quantitatively evaluated by way of feedback from participating UMCs and the completion of a web-based staff questionnaire in the following spring of each season. The IM method resulted in the development of a transparent influenza vaccination intervention implementation strategy. The intervention strategy was offered to six Dutch UMCs in a randomized in a clustered Randomized Controlled Trial (RCT), where three UMCs were chosen for intervention, and three UMCs acted as controls. A further two UMCs elected to have the intervention. The qualitative process evaluation showed that HCWs at four of the five intervention UMCs were responsive to the majority of the 11 relevant behavioural determinants resulting from the needs assessment in their intervention strategy compared with only one of three control UMCs. The quantitative evaluation among a sample of HCWs revealed that of all the developed communication materials, HCWs reported the posters as the most noticeable. Our study demonstrates that it is possible to develop a structured implementation strategy for increasing the rate of influenza vaccination by HCWs in acute health care settings. The evaluation also showed that it is impossible to
Charting the evolution of approaches employed by the Global Alliance for Vaccines and Immunizations (GAVI) to address inequities in access to immunization: a systematic qualitative review of GAVI policies, strategies and resource allocation mechanisms through an equity lens (1999?2014)
Background GAVI?s focus on reducing inequities in access to vaccines, immunization, and GAVI funds, ? both between and within countries - has changed over time. This paper charts that evolution. Methods A systematic qualitative review was conducted by searching PubMed, Google Scholar and direct review of available GAVI Board papers, policies, and program guidelines. Documents were included if they described or evaluated GAVI policies, strategies, or programs and discussed equity of access to ...
Amy M. Burdette
Conclusion: Our results suggest that interventions should focus on increasing information about the benefits of the human papillomavirus vaccine among parents of minority youth. Our findings also suggest that interventions targeting health care providers may be a useful strategy for improving vaccine uptake among adolescent males.
Mody, Nishi; Sharma, Rajeev; Agrawal, Udita; Vyas, Suresh P
Infectious agents generally use mucosal surfaces as entry port to the body thereby necessitating the need of development of mucosal vaccine as vaccination is important for disease avoidance and suppression. Vaccination through mucosal route is a promising strategy to elicit efficient immune response as parentally administered vaccines induce poor mucosal immunity in general. Safety, economy and stability are highly desired with vaccines and this can be achieved with use of delivery cargos. This review focuses on challenges related with mucosal vaccines and use of nanocarriers as suitable cargos to cater the antigen effectively to the desired site. The review also includes different factors which are to be considered regarding the performance of the nanocarriers and clinical status of these systems.
Griesenauer, Rebekah H; Kinch, Michael S
A survey of FDA-approved biologicals focused upon the development of immunotherapies over time to gain insight on the challenges and trends of vaccine development today. Areas covered: A total of 135 different immune-based therapies were broadly divided into passive or active immunotherapies. Whereas just over half of passive immunotherapies targeted infectious diseases, the vast majority of active immunotherapy products (vaccines) were directed against a handful of viral and bacterial pathogens. We also analyze changes in vaccine strategy, including the use of viable antigens and subunit approaches. Expert commentary: An analysis of vaccine innovators revealed an ever-increasing presence of the private sector and a relatively diminishing role for the public sector . Whereas North American companies have contributed to the approval of two-thirds of vaccines, European companies have regained parity in terms of hosting innovators of vaccine research and development.
Vaccine - HPV; Immunization - HPV; Gardasil; HPV2; HPV4; Vaccine to prevent cervical cancer; Genital warts - HPV vaccine; Cervical dysplasia - HPV vaccine; Cervical cancer - HPV vaccine; Cancer of the cervix - HPV vaccine; Abnormal ...
Lacum, Edwin B. Van; Goedhart, Martin J.
The aim of this study is to evaluate a teaching strategy designed to teach first-year undergraduate life sciences students at a research university how to learn to read authentic research articles. Our approach—based on the work done in the field of genre analysis and argumentation theory—means that we teach students to read research articles by teaching them which rhetorical moves occur in research articles and how they can identify these. Because research articles are persuasive by their very nature, we focused on the rhetorical moves that play an important role in authors’ arguments. We designed a teaching strategy using cognitive apprenticeship as the pedagogical approach. It was implemented in a first-year compulsory course in the life sciences undergraduate program. Comparison of the results of a pretest with those of the posttest showed that students’ ability to identify these moves had improved. Moreover, students themselves had also perceived that their ability to read and understand a research article had increased. The students’ evaluations demonstrated that they appreciated the pedagogical approach used and experienced the assignments as useful. On the basis of our results, we concluded that students had taken a first step toward becoming expert readers. PMID:26086657
Sutherland, Melissa A; Fantasia, Heidi Collins
The purpose of this article is to describe the successful recruitment methods of a study focused on a pilot intervention for rural women who were experiencing abuse and who also were at risk for sexually transmitted infections. Initial recruitment into the study was the primary challenge, and strategies to overcome recruitment difficulties are discussed. Eighty-seven women were screened, and 20 women were recruited from clinics into a 1-group pretest/posttest pilot study. The main inclusion criterion for the intervention was a past-year history of intimate partner violence (IPV). After 1 month of recruitment, only 10 women agreed to be screened for IPV. Several creative strategies were utilized in the revision of the recruitment plan, with the most successful being knitting by the research staff and incentives to participants for screening. An additional 77 women agreed to be screened for study participation within 3 months of implementing the recruitment changes. Personal involvement by the research staff and a nonthreatening and welcoming environment were necessary components for timely recruitment. Researcher flexibility and reevaluation allowed for changes to the recruitment plan that ultimately proved successful. © 2011 by the American College of Nurse-Midwives.
Chen, Yiqin; Bi, Kaixi; Wang, Qianjin; Zheng, Mengjie; Liu, Qing; Han, Yunxin; Yang, Junbo; Chang, Shengli; Zhang, Guanhua; Duan, Huigao
Focused ion beam (FIB) milling is a versatile maskless and resistless patterning technique and has been widely used for the fabrication of inverse plasmonic structures such as nanoholes and nanoslits for various applications. However, due to its subtractive milling nature, it is an impractical method to fabricate isolated plasmonic nanoparticles and assemblies which are more commonly adopted in applications. In this work, we propose and demonstrate an approach to reliably and rapidly define plasmonic nanoparticles and their assemblies using FIB milling via a simple "sketch and peel" strategy. Systematic experimental investigations and mechanism studies reveal that the high reliability of this fabrication approach is enabled by a conformally formed sidewall coating due to the ion-milling-induced redeposition. Particularly, we demonstrated that this strategy is also applicable to the state-of-the-art helium ion beam milling technology, with which high-fidelity plasmonic dimers with tiny gaps could be directly and rapidly prototyped. Because the proposed approach enables rapid and reliable patterning of arbitrary plasmonic nanostructures that are not feasible to fabricate via conventional FIB milling process, our work provides the FIB milling technology an additional nanopatterning capability and thus could greatly increase its popularity for utilization in fundamental research and device prototyping.
Cho, Hyun-Il; Jung, Soo-Hyun; Sohn, Hyun-Jung; Celis, Esteban; Kim, Tai-Gyu
Therapeutic cancer vaccines are an attractive alternative to conventional therapies for treating malignant tumors, and successful tumor eradication depends primarily on obtaining high numbers of long-lasting tumor-reactive CD8+ T cells. Dendritic cell (DC)-based vaccines constitute a promising approach for treating cancer, but in most instances low immune responses and suboptimal therapeutic effects are achieved indicating that further optimization is required. We describe here a novel vaccin...
da Costa, Adeliane Castro; Nogueira, Sarah Veloso; Kipnis, André; Junqueira-Kipnis, Ana Paula
BCG (Bacille Calmette-Guérin), an attenuated vaccine derived from Mycobacterium bovis, is the current vaccine of choice against tuberculosis (TB). Despite its protection against active TB in children, BCG has failed to protect adults against TB infection and active disease development, especially in developing countries where the disease is endemic. Currently, there is a significant effort towards the development of a new TB vaccine. This review article aims to address publications on recombi...
Chanthavilay, Phetsavanh; Reinharz, Daniel; Mayxay, Mayfong; Phongsavan, Keokedthong; Marsden, Donald E; Moore, Lynne; White, Lisa J
Cervical cancer, a preventable disease, is the third leading cause of cancer morbidity and mortality in the Lao People's Democratic Republic (Lao PDR). Since many cervical cancers are linked to human papilloma virus (HPV) infection, vaccination against this virus may lead to a reduction in these types of cancer. The study described here is the first to compare the cost-effectiveness of different HPV vaccination options in Lao PDR. A dynamic compartment model was created. The model included routine screening activities already in place, as well as theoretical interventions that included a 10-year old girl-only vaccination programme combined with/without a 10-year old boy vaccination programme and/or a catch-up component. The simulation was run over 100 years. In base case analyses, we assumed 70 % vaccination coverage with lifelong protection and 100 % efficacy against HPV types 16/18. The outcomes of interest were the incremental cost per Disability-Adjusted Life Year (DALY) averted. In base case analyses, according to the WHO definition of cost-effectiveness thresholds, vaccinating 10-year-old girls was very cost-effective. Adding a catch-up vaccination element for females aged 11-25 years was also very cost-effective, costing 1559 international dollars (I$) per DALY averted. Increasing the age limit of the catch-up vaccination component to 75 years old showed that this remained a cost-effective option (I$ 5840 per DALY averted). Adding a vaccination programme for 10-year-old boys was not found to be cost-effective unless a short time simulation (30 years or less) was considered, along with a catch-up vaccination component for both males and females. Adding a catch-up female vaccination component is more attractive than adding a 10-year-old boy vaccination component.
Rombout, J.H.W.M.; Kiron, V.
Among the novel vaccination methods, mucosal vaccination seems to possess all the desired criteria. The chapter reviews the state-of-the-art knowledge regarding this type of vaccination with a focus on their uptake, immune stimulation, and where possible, discusses their potential as future
Bonura, A; Colombo, P
Specific immunotherapy is a well established and clinically proved strategy to cure allergic reactions. The impressive boost of knowledge derived from DNA recombinant technology applied to this field allowed the identification, cloning and expression of several clinically relevant allergens. Recombinant allergens can be easily produced in a pure and reproducible way with immunological properties comparable to natural allergens and matching the requirements of pharmaceutical companies. Parietaria pollinosis is a major health problem in the Mediterranean basin with prolonged symptoms. In this review we will discuss the rational approaches to design hypoallergenic derivatives of the major allergens of this pollen, their immunological properties and possible clinical future implications.
Full Text Available Several approaches to reduce the incidence of invasive cervical cancers exist. The approach adopted should take into account contextual factors that influence the cost-effectiveness of the available options.To determine the cost-effectiveness of screening strategies combined with a vaccination program for 10-year old girls for cervical cancer prevention in Vientiane, Lao PDR.A population-based dynamic compartment model was constructed. The interventions consisted of a 10-year old girl vaccination program only, or this program combined with screening strategies, i.e., visual inspection with acetic acid (VIA, cytology-based screening, rapid human papillomavirus (HPV DNA testing, or combined VIA and cytology testing. Simulations were run over 100 years. In base-case scenario analyses, we assumed a 70% vaccination coverage with lifelong protection and a 50% screening coverage. The outcome of interest was the incremental cost per Disability-Adjusted Life Year (DALY averted.In base-case scenarios, compared to the next best strategy, the model predicted that VIA screening of women aged 30-65 years old every three years, combined with vaccination, was the most attractive option, costing 2 544 international dollars (I$ per DALY averted. Meanwhile, rapid HPV DNA testing was predicted to be more attractive than cytology-based screening or its combination with VIA. Among cytology-based screening options, combined VIA with conventional cytology testing was predicted to be the most attractive option. Multi-way sensitivity analyses did not change the results. Compared to rapid HPV DNA testing, VIA had a probability of cost-effectiveness of 73%. Compared to the vaccination only option, the probability that a program consisting of screening women every five years would be cost-effective was around 60% and 80% if the willingness-to-pay threshold is fixed at one and three GDP per capita, respectively.A VIA screening program in addition to a girl vaccination
Terpstra, C; de Smit, A J
The 1997/1998 epizootic of classical swine fever (CSF) in an area with high pig density in the Netherlands is described. The epizootic, which numbered 429 outbreaks, was controlled and finally eradicated after 14 months without resorting to vaccination. A further almost 1300 herds (1.1 million pigs) at close proximity of confirmed outbreaks were preventively culled because of the risk of having been infected. The pros and cons of this so-called "pre-emptive slaughter" are discussed. The long-lasting movement restrictions caused severe overcrowding especially in breeding farms. For reasons of animal welfare 6.5 million weaners and adult pigs had to be killed and destroyed, whereas another 2.6 million 3-17 days old piglets were euthanised to save long-term destruction capacity. The presumed routes of infection and factors influencing the epizootic are explained, as well as the various methods to bring the epizootic to a halt. The strategy for detecting outbreaks in an early stage, and the type of samples to be collected for laboratory diagnosis are emphasised from the general point of application. The direct costs of the epizootic, losses of exports not included, are estimated at US$ 2 billion.
Full Text Available Abstract Background Women who have inherited mutations in the BRCA1 or BRCA2 genes have substantially elevated risks of breast and ovarian cancer. Mutation carriers have various options, including extensive and regular surveillance, chemoprevention and risk-reducing surgery. The aim of this review is to provide an up-to-date analysis and to subsequently summarise the available literature in relation to risk-reducing strategies, with a keen focus on prophylactic surgery. Methods The literature review is facilitated by Medline and PubMed databases. The cross-referencing of the obtained articles was used to identify other relevant studies. Results Prophylactic surgery (bilateral mastectomy, bilateral salpingo-oophorectomy or a combination of both procedures has proved to be the most effective risk-reducing strategy. There are no randomised controlled trials able to demonstrate the potential benefits or harms of prophylactic surgery; therefore, the evidence has been derived from retrospective and short follow-up prospective studies, in addition to hypothetical mathematical models. Based on the current knowledge, it is reasonable to recommend prophylactic oophorectomy for BRCA1 or BRCA2 mutation carriers when childbearing is completed in order to reduce the risk of developing breast and ovarian cancer. In addition, women should be offered the options of rigorous breast surveillance, chemoprevention with anti-oestrogens--especially for carriers of BRCA2--or bilateral prophylactic mastectomy. Conclusion The selection of the most appropriate risk-reducing strategy is not a straightforward task. The impact of risk-reducing strategies on cancer risk, survival, and overall quality of life are the key criteria considered for decision-making. Notably, various other factors should be taken into consideration when evaluating individual mutation carriers' individual circumstances, namely woman's age, morbidity, type of mutation, and individual preferences and
KULPA-EDDY Jodie; SRINIVAS Geetha; HALDER Maria; BROWN Karen; DRAAYER Hans; GALVIN Jeffrey; CLAASEN Ivo; WOODLAND Ralph; DOELLING Vivian; JONES Brett; STOKES William
NICEATM and ICCVAM convened an international workshop to review the state of the science of human and veterinary vaccine potency and safety testing methods and to identify opportunities to advance new and improved methods that can further reduce, refine, and replace animal use. Six topics were addressed in detail by speakers and workshop participants and are reported in a series of six reports. This workshop report, the last in the series, addresses methods and strategies for veterinary vacci...
Full Text Available Using newer vaccine platforms which have been effective against malaria in rodent models, we tested five immunization regimens against Plasmodium knowlesi in rhesus monkeys. All vaccines included the same four P. knowlesi antigens: the pre-erythrocytic antigens CSP, SSP2, and erythrocytic antigens AMA1, MSP1. We used four vaccine platforms for prime or boost vaccinations: plasmids (DNA, alphavirus replicons (VRP, attenuated adenovirus serotype 5 (Ad, or attenuated poxvirus (Pox. These four platforms combined to produce five different prime/boost vaccine regimens: Pox alone, VRP/Pox, VRP/Ad, Ad/Pox, and DNA/Pox. Five rhesus monkeys were immunized with each regimen, and five Control monkeys received a mock vaccination. The time to complete vaccinations was 420 days. All monkeys were challenged twice with 100 P. knowlesi sporozoites given IV. The first challenge was given 12 days after the last vaccination, and the monkeys receiving the DNA/Pox vaccine were the best protected, with 3/5 monkeys sterilely protected and 1/5 monkeys that self-cured its parasitemia. There was no protection in monkeys that received Pox malaria vaccine alone without previous priming. The second sporozoite challenge was given 4 months after the first. All 4 monkeys that were protected in the first challenge developed malaria in the second challenge. DNA, VRP and Ad5 vaccines all primed monkeys for strong immune responses after the Pox boost. We discuss the high level but short duration of protection in this experiment and the possible benefits of the long interval between prime and boost.
King, E M; Gilson, R; Beddows, S; Soldan, K; Panwar, K; Young, C; Prah, P; Jit, M; Edmunds, W J; Sonnenberg, P
Human papillomavirus (HPV) vaccination of girls will have relatively little effect on HPV-related disease in men who have sex with men (MSM). We determined HPV prevalence and risk factors in MSM to inform the potential effectiveness of vaccinating MSM. Cross-sectional study of 522 MSM aged 18-40 attending a London sexual health clinic who completed a computer-assisted self-interview. Urine and two swabs (anal and penile/scrotal/perianal) were collected and tested using an in-house Luminex-based HPV genotyping system. Prevalence of DNA of the vaccine-preventable HPV types in ano-genital specimens of men was 87/511 (17.0%), 166/511 (32.5%) and 232/511 (45.4%) for the bivalent (HPV16/18), quadrivalent (HPV6/11/16/18) and nonavalent (HPV6/11/16/18/31/33/45/52/58) vaccine types, respectively. A total of 25.1% had one of the quadrivalent types, and 7.4% had 2+ types. Median age at first anal sex was 19 (IQR 17-23) and at first clinic attendance was 24 (IQR 20-27). The increase in the odds of any HPV infection per year of age was 4.7% (95% CI 1.2-8.4). On the basis of the current infection status, most MSM, even among a high-risk population attending a sexual health clinic, are not currently infected with the vaccine-type HPV. A targeted vaccination strategy for MSM in the UK could have substantial benefits.
Clarke, Steve; Giubilini, Alberto; Walker, Mary Jean
ABSTRACT Vaccine refusal occurs for a variety of reasons. In this article we examine vaccine refusals that are made on conscientious grounds; that is, for religious, moral, or philosophical reasons. We focus on two questions: first, whether people should be entitled to conscientiously object to vaccination against contagious diseases (either for themselves or for their children); second, if so, to what constraints or requirements should conscientious objection (CO) to vaccination be subject. ...
Midthun, K; Kapikian, A Z
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...
Behzadi, Elham; Halabian, Raheleh; Hosseini, Hamideh Mahmoodzadeh; Fooladi, Abbas Ali Imani
DNA vaccination -a third generation vaccine-is a modern approach to stimulate humoral and cellular responses against different diseases such as infectious diseases, cancer and autoimmunity. These vaccines are composed of a gene that encodes sequences of a desired protein under control of a proper (eukaryotic or viral) promoter. Immune response following DNA vaccination is influenced by the route and the dose of injection. In addition, antigen presentation following DNA administration has three different mechanisms including antigen presentation by transfected myocytes, transfection of professional antigen presenting cells (APCs) and cross priming. Recently, it has been shown that bacterial toxins and their components can stimulate and enhance immune responses in experimental models. A study demonstrated that DNA fusion vaccine encoding the first domain (DOM) of the Fragment C (FrC) of tetanus neurotoxin (CTN) coupled with tumor antigen sequences is highly immunogenic against colon carcinoma. DNA toxin vaccines against infectious and autoimmune diseases are less studied until now. All in all, this novel approach has shown encouraging results in animal models, but it has to go through adequate clinical trials to ensure its effectiveness in human. However, it has been proven that these vaccines are safe, multifaceted and simple and can be used widely in organisms which may be of advantage to public health in the near future. This paper outlines the mechanism of the action of DNA vaccines and their possible application for targeting infectious diseases, cancer and autoimmunity. Copyright © 2016 Elsevier Ltd. All rights reserved.
Medina-Marino, Andrew; Reynolds, Debra; Finley, Carol; Hays, Susan; Jones, Jane; Soyemi, Kenneth
During January 2010, 2 infants from an Amish community in east-central Illinois were hospitalized with pertussis. The local health department (LDH) intervened to control disease transmission, identify contributing factors, and determine best communications methods to improve vaccination coverage. A retrospective cohort study was conducted using public health surveillance data to determine the extent of the outbreak; the standard Centers for Disease Control and Prevention and Council of State and Territorial Epidemiologists case definition for pertussis was used. The standardized Illinois Department of Public Health pertussis patient interview form was used to collect demographic, symptom, vaccination history, and treatment history information. To control disease transmission, LDH staff worked with the Amish community to promote a vaccination campaign during February 6-April 30, 2010. Forty-seven cases were identified, with onsets during December 2009-March 2010. Median age was 7 (interquartile range 1-12) years. Nineteen (40%) patients were male; 39 (83%) were aged Amish community members were administered 254 pertussis-containing vaccines. Targeted health communication and outreach resulted in a successful vaccine campaign and long-running monthly vaccination clinic. Amish do not universally reject vaccines, and their practices regarding vaccination are not static. No claim to original US government works.
Pérez García-Pando, C.; Thomson, M. C.; Stanton, M. C.; Diggle, P. J.; Miller, R. L.; Perlwitz, J. P.; Ceccato, P.
Epidemics of meningococcal meningitis occur in sub-Saharan Africa during the dry season, a period when the region is affected by the Harmattan, a dry and dusty northeasterly trade wind blowing from the Sahara into the Gulf of Guinea. Although the mechanisms remain unclear, the location and seasonality of meningitis epidemics suggest that environmental factors, such as low absolute or relative humidity, high temperatures, and dusty atmospheric conditions play an important role. Using a 20-year time series of meningitis incidence in Niger we examined the potential of statistical models to predict seasonal incidence based on data that would be operationally available, such as climate and dust, population and previous incidence. We used surface dust concentration estimates from a model given the paucity of direct in situ measurements especially at district level. The soil dust aerosol component of the model was thoroughly evaluated with existing satellite and in situ data over the region of interest showing daily aerosol optical depth correlations around 0.6 (p < 0.05). Our results show that wind and dust information along with incidence in the early dry season predict a significant part of the year-to-year variability of the seasonal incidence at both national and district levels. Such a model could provide an early-season alert when wind, dust, and other conditions are conducive to an epidemic. We additionally discuss how this research has focused at "getting science into practice" by engaging with practitioner communities to inform operational decision-making for reactive vaccination.
Holst, Peter Johannes; Jensen, Benjamin Anderschou Holbech; Ragonnaud, Emeline
In this study, we compared adenoviral vaccine vectors with the capacity to induce equally potent immune responses against non-dominant and immunodominant epitopes of murine lymphocytic choriomeningitis virus (LCMV). Our results demonstrate that vaccination targeting non-dominant epitopes...... challenge with live virus, the CD8+ T cells specific for vaccine-encoded epitopes, displayed a phenotype typically associated with prolonged/persistent antigenic stimulation marked by high levels of KLRG-1, as compared to T cells reacting to epitopes not included in the vaccine. Notably, this association...... facilitates potent virus-induced T-cell responses against immunodominant epitopes during subsequent challenge with highly invasive virus. In contrast, when an immunodominant epitope was included in the vaccine, the T-cell response associated with viral challenge remained focussed on that epitope. Early after...
Van Lacum, Edwin B; Ossevoort, Miriam A; Goedhart, Martin J
The aim of this study is to evaluate a teaching strategy designed to teach first-year undergraduate life sciences students at a research university how to learn to read authentic research articles. Our approach-based on the work done in the field of genre analysis and argumentation theory-means that we teach students to read research articles by teaching them which rhetorical moves occur in research articles and how they can identify these. Because research articles are persuasive by their very nature, we focused on the rhetorical moves that play an important role in authors' arguments. We designed a teaching strategy using cognitive apprenticeship as the pedagogical approach. It was implemented in a first-year compulsory course in the life sciences undergraduate program. Comparison of the results of a pretest with those of the posttest showed that students' ability to identify these moves had improved. Moreover, students themselves had also perceived that their ability to read and understand a research article had increased. The students' evaluations demonstrated that they appreciated the pedagogical approach used and experienced the assignments as useful. On the basis of our results, we concluded that students had taken a first step toward becoming expert readers. © 2014 E. B. Van Lacum et al. CBE—Life Sciences Education © 2014 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).
Finkelstein, Stanley M; Celebrezze, Margaret; Cady, Rhonda; Lunos, Scott; Looman, Wendy S
Obtaining complete and timely subject data is key to the success of clinical trials, particularly for studies requiring data collected from subjects at home or other remote sites. A multifaceted strategy for data collection in a randomized controlled trial (RCT) focused on care coordination for children with medical complexity is described. The influences of data collection mode, incentives, and study group membership on subject response patterns are analyzed. Data collection included monthly healthcare service utilization (HCSU) calendars and annual surveys focused on care coordination outcomes. One hundred sixty-three families were enrolled in the 30-month TeleFamilies RCT. Subjects were 2-15 years of age at enrollment. HCSU data were collected by parent/guardian self-report using mail, e-mail, telephone, or texting. Surveys were collected by mail. Incentives were provided for completed surveys after 8 months to improve collection returns. Outcome measures were the number of HCSU calendars and surveys returned, the return interval, data collection mode, and incentive impact. Return rates of 90% for HCSU calendars and 82% for annual surveys were achieved. Mean return intervals were 72 and 65 days for HCSU and surveys, respectively. Survey response increased from 55% to 95% after introduction of a gift card and added research staff. High return rates for HCSU calendars and health-related surveys are attainable but required a flexible and personnel-intensive approach to collection methods. Family preference for data collection approach should be obtained at enrollment, should be modified as needed, and requires flexible options, training, intensive staff/family interaction, and patience.
Lau, Chuen-Yen; Wahl, Bryan; Foo, Wendell K S
Since vaccination is critical in responding to smallpox exposure, vaccination strategies must be evaluated during bioterrorism preparedness. Information on historical factors, smallpox characteristics, public health capabilities and hypothetical attack scenarios was used to evaluate major vaccination strategies. In event of a smallpox attack, the optimal strategy is situational, mass vaccination may be best for dense island populations such as Oahu.
Recent introduction of strategies to reduce antibiotic use in food animal production implies an increased use of vaccines in order to prevent the economic impact of several important diseases in swine. Good Vaccination Practice (GVP) is an overall approach on the swine farm aiming to obtain maximal efficacy of vaccination through good storage, preparation and finally correct application to the target animals. In order to have a better insight into GVP on swine farms and the vaccine storage conditions, a survey on vaccination practices was performed on a farmers' fair and temperatures in the vaccine storage refrigerators were measured during farm visits over a period of 1 year. The survey revealed that knowledge on GVP, such as vaccine storage and handling, needle management and injection location could be improved. Less than 10% had a thermometer in their vaccine storage refrigerator on the moment of the visit. Temperature measurement revealed that only 71% of the measured refrigerators were in line with the recommended temperature range of +2 °C to +8 °C. Both below +2 °C and above +8 °C temperatures were registered during all seasons of the year. Compliance was lower during summer with an average temperature of 9.2 °C while only 43% of the measured temperatures were within the recommended range. The present study clearly showed the need for continuous education on GVP for swine veterinarians, swine farmers and their farm personnel in general and vaccine storage management in particular. In veterinary medicine, the correct storage of vaccines is crucial since both too low and too high temperatures can provoke damage to specific vaccine types. Adjuvanted killed or subunit vaccines can be damaged (e.g. structure of aluminiumhydroxide in adjuvans) by too low temperatures (below 0 °C), whereas lyophilized live vaccines are susceptible (e.g. loss of vaccine potency) to heat damage by temperatures above +8 °C. In conclusion, knowledge and awareness of GVP
Gil Cuesta, Julita; Aavitsland, Preben; Englund, Hélène
During the 2009/10 influenza A(H1N1)pdm09 pandemic, the five Nordic countries adopted different approaches to pandemic vaccination. We compared pandemic vaccination strategies and severe influenza outcomes, in seasons 2009/10 and 2010/11 in these countries with similar influenza surveillance...... systems. We calculated the cumulative pandemic vaccination coverage in 2009/10 and cumulative incidence rates of laboratory confirmed A(H1N1)pdm09 infections, intensive care unit (ICU) admissions and deaths in 2009/10 and 2010/11. We estimated incidence risk ratios (IRR) in a Poisson regression model...... to compare those indicators between Denmark and the other countries. The vaccination coverage was lower in Denmark (6.1%) compared with Finland (48.2%), Iceland (44.1%), Norway (41.3%) and Sweden (60.0%). In 2009/10 Denmark had a similar cumulative incidence of A(H1N1)pdm09 ICU admissions and deaths compared...
Nyamathi, AM; Fahey, JL; Sands, H; Casillas, AM
Vaccination is one of our most powerful antiviral strategies. Despite the emergence of deadly viruses such as Ebola virus, vaccination efforts have focused mainly on childhood communicable diseases. Although Ebola virus was once believed to be limited to isolated outbreaks in distant lands, forces of globalization potentiate outbreaks anywhere in the world through incidental transmission. Moreover, since this virus has already been transformed into weapongrade material, the potential exists f...
Williamson, Eric M L; Chahin, Salim; Berger, Joseph R
Vaccinations help prevent communicable disease. To be valuable, a vaccine's ability to prevent disease must exceed the risk of adverse effects from administration. Many vaccines present no risk of infection as they are comprised of killed or non-infectious components while other vaccines consist of live attenuated microorganisms which carry a potential risk of infection-particularly, in patients with compromised immunity. There are several unique considerations with respect to vaccination in the multiple sclerosis (MS) population. First, there has been concern that vaccination may trigger or aggravate the disease. Second, disease-modifying therapies (DMTs) employed in the treatment of MS may increase the risk of infectious complications from vaccines or alter their efficacy. Lastly, in some cases, vaccination strategies may be part of the treatment paradigm in attempts to avoid complications of therapy.
Paul, Proma; Fabio, Anthony
School-based vaccination is becoming a more widely considered method of delivering HPV immunizations to an adolescent population; however, many countries do not have experience with delivering adolescent vaccines or school-based programs. This literature review will summarize the experiences from countries implementing non-health facility-based and health facility-based vaccination programs and assess HPV vaccine coverage. In October 2012, a systematic search in PubMed for studies related to the evaluation of national/regional, pilot, or demonstration HPV immunization programs that worked within existing health system yielded nine articles, representing seventeen countries. School-based programs achieved high HPV vaccination coverage rates in 9 to 13-year-old girls across the different studies and geographic locations, suggesting non-health facility-based programs are possible for HPV vaccine introduction. Grade-based, compared to age-based, eligibility criteria may be easier to implement in school settings. More studies are needed to explore the methods to standardize estimates for HPV vaccine coverage so that programs can be appropriately evaluated. Copyright © 2013 Elsevier Ltd. All rights reserved.
Chiarelli, Roberto; Martino, Chiara; Agnello, Maria; Bosco, Liana; Roccheri, Maria Carmela
Autophagy is used by organisms as a defense strategy to face environmental stress. This mechanism has been described as one of the most important intracellular pathways responsible for the degradation and recycling of proteins and organelles. It can act as a cell survival mechanism if the cellular damage is not too extensive or as a cell death mechanism if the damage/stress is irreversible; in the latter case, it can operate as an independent pathway or together with the apoptotic one. In this review, we discuss the autophagic process activated in several aquatic organisms exposed to different types of environmental stressors, focusing on the sea urchin embryo, a suitable system recently included into the guidelines for the use and interpretation of assays to monitor autophagy. After cadmium (Cd) exposure, a heavy metal recognized as an environmental toxicant, the sea urchin embryo is able to adopt different defense mechanisms, in a hierarchical way. Among these, autophagy is one of the main responses activated to preserve the developmental program. Finally, we discuss the interplay between autophagy and apoptosis in the sea urchin embryo, a temporal and functional choice that depends on the intensity of stress conditions.
Cottingham, Matthew G; van Maurik, Andre; Zago, Manola; Newton, Angela T; Anderson, Richard J; Howard, M Keith; Schneider, Jörg; Skinner, Michael A
The FP9 strain of F has been described as a more immunogenic recombinant vaccine vector than the Webster FPV-M (FPW) strain (R. J. Anderson et al., J. Immunol. 172:3094-3100, 2004). This study expands the comparison to include two separate recombinant antigens and multiple, rather than single, independent viral clones derived from the two strains. Dual-poxvirus heterologous prime-boost vaccination regimens using individual clones of recombinant FP9 or FPW in combination with recombinant modified V Ankara expressing the same antigen were evaluated for their ability to elicit T-cell responses against recombinant antigens from Plasmodium berghei (circumsporozoite protein) or human immunodeficiency virus type 1 (a Gag-Pol-Nef fusion protein). Gamma interferon enzyme-linked immunospot assay and fluorescence-activated cell sorting assays of the responses to specific epitopes confirmed the approximately twofold-greater cellular immunogenicity of FP9 compared to FPW, when given as the priming or boosting immunization. Equality of transgene expression in mouse cells infected with the two strains in vitro was verified by Western blotting. Directed partial sequence analysis and PCR analysis of FPW and comparison to available whole-genome sequences revealed that many loci that are mutated in the highly attenuated and culture-adapted FP9 strain are wild type in FPW, including the seven multikilobase deletions. These "passage-specific" alterations are hypothesized to be involved in determining the immunogenicity of fowlpox virus as a recombinant vaccine vector.
Novel vaccine strategies include the so-called subunit vaccines, which encompass only the part of the pathogen to which immune recognition results in protection. The high purity of these vaccines make adverse events less likely, but it also makes the vaccines less immunogenic and therefore potentially less effective. Vaccine adjuvants that increase and modulate the immunogenicity of the vaccine are therefore added to solve this problem. Besides aluminum salts, which have been used in vaccines for 90 years, a number of novel vaccine adjuvants have been included in licensed vaccines over the last 30 years. Increasing insight into immunological mechanisms and how to manipulate them has replaced empirical with rational design of adjuvants, leading to vaccine adjuvants with increased and customized immunogenicity profiles without compromising vaccine safety.
Howlett, Roberta I; Miller, Anthony B; Pasut, George; Mai, Verna
... with the availability of preventive HPV vaccines. Canada is comprised of ten provinces and three territories; about 40% of Canadians reside in Ontario. Similar to rates across Canada, Ontario i...
Lu, Shan; Wang, Shixia
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
Full Text Available The development of a safe and effective AD vaccine requires a delicate balance between providing an adequate anti-Abeta antibody response sufficient to provide therapeutic benefit, while eliminating an adverse T cell-mediated proinflammatory autoimmune response. To achieve this goal we have designed a prototype chemokine-based DNA epitope vaccine expressing a fusion protein that consists of 3 copies of the self-B cell epitope of Abeta(42 (Abeta(1-11 , a non-self T helper cell epitope (PADRE, and macrophage-derived chemokine (MDC/CCL22 as a molecular adjuvant to promote a strong anti-inflammatory Th2 phenotype.We generated pMDC-3Abeta(1-11-PADRE construct and immunized 3xTg-AD mouse model starting at age of 3-4 months old. We demonstrated that prophylactic immunizations with the DNA epitope vaccine generated a robust Th2 immune response that induced high titers of anti-Abeta antibody, which in turn inhibited accumulation of Abeta pathology in the brains of older mice. Importantly, vaccination reduced glial activation and prevented the development of behavioral deficits in aged animals without increasing the incidence of microhemorrhages.Data from this transitional pre-clinical study suggest that our DNA epitope vaccine could be used as a safe and effective strategy for AD therapy. Future safety and immunology studies in large animals with the goal to achieve effective humoral immunity without adverse effects should help to translate this study to human clinical trials.
Full Text Available Salmonid rickettsial septicemia is a serious, infectious disease in Chilean salmon farming caused by Piscirickettsia salmonis, causing heavy losses to the salmonid industry. P. salmonis belongs to the Gammaproteobacteria, order Thiotrichales. SRS was first described in Chile in 1989, and infection with P. salmonis has since been described from a high number of fish species and in several geographic regions globally. P. salmonis infection of salmonids causes multifocal, necrotic areas of internal organs like liver, kidney and spleen. Histologically and immunologically the tissue response is formation of granulomas, often with central suppuration. The exact sequence of infection is not known but bacteria likely gain access to internal organs through mucosal surfaces and when infected, fish carry bacteria in macrophages. It has not been fully determined if the bacterium resides in the cytosol or hide within vesicular structures intracellularly, although there are indications that in vitro infection results in actin reorganization and formation of actin-coated vesicle within which the bacterium resides. Protection against lethal challenge is well documented in lab scale experiments but protection from vaccination has proven more difficult to attain long term under field conditions. Current vaccination protocols include whole cell, inactivated and adjuvanted vaccines for injection for primary immunization followed by oral boost where timing of boost delivery is followed by measuring circulating antibody levels against the pathogen. Documentation also exist that there is correlation between antibody titers and protection against mortality. Future vaccination regimes will likely also include live, attenuated vaccines or other technologies such as DNA vaccination. So far there is no documentation available for live vaccines and for DNA vaccines, studies have been unsuccessful under laboratory conditions.
Gayet, Rémi; Bioley, Gilles; Rochereau, Nicolas; Paul, Stéphane; Corthésy, Blaise
Salmonella enterica subspecies enterica includes several serovars infecting both humans and other animals and leading to typhoid fever or gastroenteritis. The high prevalence of associated morbidity and mortality, together with an increased emergence of multidrug-resistant strains, is a current global health issue that has prompted the development of vaccination strategies that confer protection against most serovars. Currently available systemic vaccine approaches have major limitations, including a reduced effectiveness in young children and a lack of cross-protection among different strains. Having studied host-pathogen interactions, microbiologists and immunologists argue in favor of topical gastrointestinal administration for improvement in vaccine efficacy. Here, recent advances in this field are summarized, including mechanisms of bacterial uptake at the intestinal epithelium, the assessment of protective host immunity, and improved animal models that closely mimic infection in humans. The pros and cons of existing vaccines are presented, along with recent progress made with novel formulations. Finally, new candidate antigens and their relevance in the refined design of anti-Salmonella vaccines are discussed, along with antigen vectorization strategies such as nanoparticles or secretory immunoglobulins, with a focus on potentiating mucosal vaccine efficacy. Copyright © 2017 American Society for Microbiology.
Diemert, David J; Bethony, Jeffrey M; Hotez, Peter J
Hookworm infection caused by the soil-transmitted nematodes Necator americanus and Ancylostoma duodenale is one of the most common parasitic infections worldwide. Although not directly responsible for substantial mortality, it causes significant morbidity in the form of chronic anemia and protein malnutrition. Current global control efforts based on periodic mass anthelmintic administration are unsustainable, and new control strategies must be developed. This review describes progress in the development of vaccines against hookworm infection, including the preclinical and initial clinical testing of the N. americanus Ancylostoma Secreted Protein-2 Hookworm Vaccine. Plans call for eventual development of a vaccine that will combine at least 2 hookworm antigens--one targeting the larval stage of the life cycle and another targeting the adult worm living in the gastrointestinal tract.
Laguzet, Laetitia; Turinici, Gabriel
International audience; This work focuses on optimal vaccination policies for an Susceptible - Infected - Recovered (SIR) model; the impact of the disease is minimized with respect to the vaccination strategy. The problem is formulated as an optimal control problem and we show that the value function is the unique viscosity solution of an Hamilton - Jacobi - Bellman (HJB) equation. This allows to find the best vaccination policy. At odds with existing literature, it is seen that the value fun...
Dempsey, Amanda F; Maertens, Julie; Beaty, Brenda L; O'Leary, Sean T
Inadequate provider time for addressing parents' questions and concerns about adolescent vaccines is a barrier to vaccine utilization. We sought to determine how different recruitment strategies impact the degree of engagement with an intervention that provided this information via an iPad placed in a clinical setting. We provided to three pediatric practices in the Denver area the "Teen VaxScene" web site that generates individually customized information for parents about adolescent vaccines. Three recruitment strategies were assessed for their impact on parental use of the intervention as follows: passive recruitment using posters to advertise a "kiosk" version of the intervention; posters plus a $10 incentive for using the kiosk; and posters plus a $10 incentive plus decoupling the iPad from the kiosks to enable "roving." We assessed the engagement with the intervention at multiple levels including log in, consent, and completion of a baseline survey and viewing individually tailored web pages. Surveys were used to assess barriers to using the intervention. During the 14-month study period, 693 people had contact with the iPad, 199 consented, and 48 completed the survey to enable creation of tailored content; and 42 used the tailored site. Five times as many parents (n = 40) consented to participation during the 2 months when the intervention was "roving" than during the 10-month "passive" recruitment period. Engagement with the tailored material was low, with most users viewing only the "table of contents" pages. Utilizers and nonutilizers of the intervention had similar demographic characteristics. Enabling the iPad to "rove" in the clinic greatly increased the proportion of parents consenting to use the intervention. However, meaningful engagement with the material was low. Further research is needed to understand the most effective and time efficient ways to provide vaccine-related educational information to parents of adolescents. Copyright © 2015 Society
Jaeger, Veronika K; Tschudi, Nadine; Rüegg, Rolanda; Hatz, Christoph; Bühler, Silja
Vulnerable individuals such as elderly, children/adolescents and pregnant/breastfeeding women increasingly travel overseas. We describe the travel and vaccination patterns of these groups at the largest Travel Clinic in Switzerland especially focusing on travel to yellow fever and malaria-endemic countries, and yellow fever vaccination (YFV) and malaria medications. An analysis of pre-travel visits between 2010 and 2012 at the Travel Clinic of the University of Zurich, was performed assessing differences between the elderly, young and middle-aged travelers as well as between pregnant/breastfeeding and other female travelers. Overall, the vulnerable groups did not differ from other travelers regarding their travel patterns. YFV was the most often administered vaccine to elderly travelers; half of them received it for the first time. More than 30% of children/adolescents received YFV, but no child below six months was vaccinated. 80% of young travelers and a similar percentage of pregnant women went to malaria-endemic regions. Twenty-five pregnant/breastfeeding women traveled to YF endemic areas. Travel patterns of vulnerable travelers are comparable to those of other travelers. In view of the limited data on malaria medications and precautions against YFV during pregnancy and at the extreme ages of life, giving travel advice to these groups is challenging. Copyright © 2015 Elsevier Ltd. All rights reserved.
Evaluating the most effective distribution strategies to assure administration of pandemic H1N1 influenza vaccine to New York State children and adolescents: evaluation using the New York State Immunization Information System.
Bednarczyk, Robert A; DuVall, Sarah; Meldrum, Megan D; Flynn, Michael K; Santilli, Loretta A; Easton, Delia E; Sharma, Priya; Blog, Debra S; Zansky, Shelley M; McNutt, Louise-Anne; Birkhead, Guthrie S
To examine differences in H1N1 influenza vaccine distribution strategies that may impact the ability to rapidly administer vaccine during a pandemic or public health emergency. Retrospective evaluation of immunization data in the New York State Immunization Information System (NYSIIS). Analysis of existing NYSIIS data. Children and adolescents younger than 19 years for whom information on at least 1 H1N1 influenza vaccine was present in NYSIIS. Median time to administer vaccines to children and adolescents younger than 19 years by December 31, 2009, by county; venue of H1N1 vaccine administration (local health department [LHD] or private medical provider); comparison of immunization-seeking behavior for routine childhood vaccinations and H1N1 vaccine. A total of 459 189 first or only doses of H1N1 influenza vaccine were recorded in NYSIIS as being administered to New York State, outside of New York City, children aged less than 19 years, between October 2, 2009, and December 31, 2009. Overall, LHD administered 31% of H1N1 vaccine doses; in counties having population less than 100,000, LHD administered 63% of H1N1 doses compared with 23% in counties having population more than 100,000. Time to median administration was faster for LHD in smaller counties and similar for LHD and private medical providers in larger counties. Children who always received routine childhood immunizations either within or outside of their county of residence often had the same practice for H1N1 vaccine, with 85% of children following these patterns. Children who did not follow these patterns were more likely to receive H1N1 influenza vaccine through LHD. Local health departments were able to rapidly administer large quantities of H1N1 influenza vaccine, and patterns of health care seeking relying on increased use of LHD needs to be further studied for future public health emergency planning.
Full Text Available Abstract The use of live bacteria to induce an immune response to itself or to a carried vaccine component is an attractive vaccine strategy. Advantages of live bacterial vaccines include their mimicry of a natural infection, intrinsic adjuvant properties and their possibility to be administered orally. Derivatives of pathogenic and non-pathogenic food related bacteria are currently being evaluated as live vaccines. However, pathogenic bacteria demands for attenuation to weaken its virulence. The use of bacteria as vaccine delivery vehicles implies construction of recombinant strains that contain the gene cassette encoding the antigen. With the increased knowledge of mucosal immunity and the availability of genetic tools for heterologous gene expression the concept of live vaccine vehicles gains renewed interest. However, administration of live bacterial vaccines poses some risks. In addition, vaccination using recombinant bacteria results in the release of live recombinant organisms into nature. This places these vaccines in the debate on application of genetically modified organisms. In this review we give an overview of live bacterial vaccines on the market and describe the development of new live vaccines with a focus on attenuated bacteria and food-related lactic acid bacteria. Furthermore, we outline the safety concerns and identify the hazards associated with live bacterial vaccines and try to give some suggestions of what to consider during their development.
Horn, J; Damm, O; Kretzschmar, M E E; Deleré, Y; Wichmann, O; Kaufmann, A M; Garbe, E; Krämer, A; Greiner, W; Mikolajczyk, R T
In Germany, vaccination against the most oncogenic HPV types 16/18 is recommended by the Standing Committee on Vaccination (STIKO) for 12-17 year old girls since March 2007. We developed a dynamic mathematical model for the natural history and transmission of HPV infections to estimate the impact of vaccination on incidence and mortality of cervical cancer and its pre-stages, and on anogenital warts. We focused on an extensive model calibration to epidemiologic data for all stages of the natural history model as well as on a detailed implementation of cervical cancer screening modalities in Germany. Our model predicts first a substantial reduction of cervical cancer incidence and mortality over the next 30 years, which is mainly attributable to an increase in screening participation in the 1990s and not to HPV vaccination, followed by a further reduction attributable to vaccination. Over the next 100 years, HPV vaccination will prevent approximately 37% of cervical cancer cases even if vaccination coverage is only 50% (as currently observed in Germany). Consideration of cross-protection results in a further reduction of approximately 7% of all cervical cancer cases for the bivalent and about 5% for the quadrivalent vaccine in our model. Vaccination of boys was only reasonable if moderate to high vaccination coverage in girls was not achieved. Strategies should be implemented in Germany to increase HPV vaccination coverage among girls thereby making better use of the demonstrated benefits of the vaccine. Copyright © 2013 Elsevier Ltd. All rights reserved.
MA Badhul Haq
Full Text Available White spot syndrome virus (WSSV, the causative virus of the disease, is found in most shrimp farming areas of the world, where it causes large economic losses to the shrimp farming industry. The potentially fatal virus has been found to be a threat not only to all shrimp species, but also to other marine and freshwater crustaceans, such as crab and crayfish. To date, no effective prophylactic treatment measures are available for viral infections in shrimp and other crustaceans. Due to current aquaculture practices and the broad host range of WSSV, intervention strategies including vaccination against this virus would be pivotal to save and protect shrimp farming. Several achievements have been attained in the search of novel vaccines for WSSV. DNA vaccination, recombinant vaccines, oral vaccination techniques and gene therapy are some of the thrust areas of focus for scientists and researchers. This review article highlights the recent trends in the development of WSSV vaccines either as DNA vaccines or recombinant vaccines and their functioning strategies as suggested by the researchers worldwide.
Allam, Ahmed; Schulz, Peter J
Background One of people’s major motives for going online is the search for health-related information. Most consumers start their search with a general search engine but are unaware of the fact that its sorting and ranking criteria do not mirror information quality. This misconception can lead to distorted search outcomes, especially when the information processing is characterized by heuristic principles and resulting cognitive biases instead of a systematic elaboration. As vaccination opponents are vocal on the Web, the chance of encountering their non‒evidence-based views on immunization is high. Therefore, biased information processing in this context can cause subsequent impaired judgment and decision making. A technological debiasing strategy could counter this by changing people’s search environment. Objective This study aims at testing a technological debiasing strategy to reduce the negative effects of biased information processing when using a general search engine on people’s vaccination-related knowledge and attitudes. This strategy is to manipulate the content of Google’s knowledge graph box, which is integrated in the search interface and provides basic information about the search topic. Methods A full 3x2 factorial, posttest-only design was employed with availability of basic factual information (comprehensible vs hardly comprehensible vs not present) as the first factor and a warning message as the second factor of experimental manipulation. Outcome variables were the evaluation of the knowledge graph box, vaccination-related knowledge, as well as beliefs and attitudes toward vaccination, as represented by three latent variables emerged from an exploratory factor analysis. Results Two-way analysis of variance revealed a significant main effect of availability of basic information in the knowledge graph box on participants’ vaccination knowledge scores (F2,273=4.86, P=.01), skepticism/fear of vaccination side effects (F2,273=3.5, P=.03
Ludolph, Ramona; Allam, Ahmed; Schulz, Peter J
One of people's major motives for going online is the search for health-related information. Most consumers start their search with a general search engine but are unaware of the fact that its sorting and ranking criteria do not mirror information quality. This misconception can lead to distorted search outcomes, especially when the information processing is characterized by heuristic principles and resulting cognitive biases instead of a systematic elaboration. As vaccination opponents are vocal on the Web, the chance of encountering their non‒evidence-based views on immunization is high. Therefore, biased information processing in this context can cause subsequent impaired judgment and decision making. A technological debiasing strategy could counter this by changing people's search environment. This study aims at testing a technological debiasing strategy to reduce the negative effects of biased information processing when using a general search engine on people's vaccination-related knowledge and attitudes. This strategy is to manipulate the content of Google's knowledge graph box, which is integrated in the search interface and provides basic information about the search topic. A full 3x2 factorial, posttest-only design was employed with availability of basic factual information (comprehensible vs hardly comprehensible vs not present) as the first factor and a warning message as the second factor of experimental manipulation. Outcome variables were the evaluation of the knowledge graph box, vaccination-related knowledge, as well as beliefs and attitudes toward vaccination, as represented by three latent variables emerged from an exploratory factor analysis. Two-way analysis of variance revealed a significant main effect of availability of basic information in the knowledge graph box on participants' vaccination knowledge scores (F2,273=4.86, P=.01), skepticism/fear of vaccination side effects (F2,273=3.5, P=.03), and perceived information quality (F2
Joshi, Anuradha Sujai; Ganjiwale, Jaishree Deepak; Varma, Jagdish; Singh, Praveen; Modi, Jyoti Nath; Singh, Tejinder
Background: Globally, students with top academic performance and high intellectual capacity usually opt to study medicine. However, once students get enrolled, their academic performance varies widely. Such variations appear to be determined by various factors, one of them being types of learning strategies adopted by students. The learning strategies utilized by the students with better academic performance are likely to be more effective learning strategies. Aims and Objectives: The objecti...
Fadda, Marta; Allam, Ahmed; Schulz, Peter J
Despite being committed to the immunization agenda set by the WHO, Italy is currently experiencing decreasing vaccination rates and increasing incidence of vaccine-preventable diseases. Our aim is to analyze Italian online debates on pediatric immunizations through a content analytic approach in order to quantitatively evaluate and summarize users' arguments and information sources. Threads were extracted from 3 Italian forums. Threads had to include the keyword Vaccin* in the title, focus on childhood vaccination, and include at least 10 posts. They had to have been started between 2008 and June 2014. High inter-coder reliability was achieved. Exploratory analysis using k-means clustering was performed to identify users' posting patterns for arguments about vaccines and sources. The analysis included 6544 posts mentioning 6223 arguments about pediatric vaccinations and citing 4067 sources. The analysis of argument posting patterns included users who published a sufficient number of posts; they generated 85% of all arguments on the forum. Dominating patterns of three groups were identified: (1) an anti-vaccination group (n=280) posted arguments against vaccinations, (2) a general pro-vaccination group (n=222) posted substantially diverse arguments supporting vaccination and (3) a safety-focused pro-vaccination group (n=158) mainly forwarded arguments that questioned the negative side effects of vaccination. The anti-vaccination group was shown to be more active than the others. They use multiple sources, own experience and media as their cited sources of information. Medical professionals were among the cited sources of all three groups, suggesting that vaccination-adverse professionals are gaining attention. Knowing which information is shared online on the topic of pediatric vaccinations could shed light on why immunization rates have been decreasing and what strategies would be best suited to address parental concerns. This suggests there is a high need for
Full Text Available Abstract Cancer vaccines are the promising tools in the hands of the clinical oncologist. Many tumor-associated antigens are excellent targets for immune therapy and vaccine design. Optimally designed cancer vaccines should combine the best tumor antigens with the most effective immunotherapy agents and/or delivery strategies to achieve positive clinical results. Various vaccine delivery systems such as different routes of immunization and physical/chemical delivery methods have been used in cancer therapy with the goal to induce immunity against tumor-associated antigens. Two basic delivery approaches including physical delivery to achieve higher levels of antigen production and formulation with microparticles to target antigen-presenting cells (APCs have demonstrated to be effective in animal models. New developments in vaccine delivery systems will improve the efficiency of clinical trials in the near future. Among them, nanoparticles (NPs such as dendrimers, polymeric NPs, metallic NPs, magnetic NPs and quantum dots have emerged as effective vaccine adjuvants for infectious diseases and cancer therapy. Furthermore, cell-penetrating peptides (CPP have been known as attractive carrier having applications in drug delivery, gene transfer and DNA vaccination. This review will focus on the utilization of different vaccine delivery systems for prevention or treatment of cancer. We will discuss their clinical applications and the future prospects for cancer vaccine development.
Nghi, Nguyen Quy; Lamontagne, D Scott; Bingham, Allison; Rafiq, Mirriam; Mai, Le Thi Phuong; Lien, Nguyen Thi Phuong; Khanh, Nguyen Cong; Hong, Duong Thi; Huyen, Dang Thi Thanh; Tho, Nguyen Thi Thi; Hien, Nguyen Tran
Formative research is a useful tool for designing new health interventions. This paper presents key findings from formative research conducted in Vietnam to guide human papillomavirus (HPV) vaccine introduction. We explored the sociocultural environment, health system capacity and the policy-making process using a combined quantitative and qualitative methodology. Data collection was done through literature review, in-depth interviews, focus group discussions, observation checklists and a structured questionnaire on knowledge, attitudes and practices. Populations of interest included 11- to 14-year-old girls, their parents, community leaders, teachers, health workers, health and education officials, and policy-makers at all levels. Although HPV vaccines are new, we found high potential acceptance among parents and girls. HPV vaccine introduction was also favourably supported by health professionals if assurances for system preparedness, e.g. cold chain and human resources, were made. There were no significant barriers from the policy perspective that would prevent the introduction of a new vaccine. However, several concerns related to this new vaccine would need to be adequately addressed before implementation. Our findings provide options for potential vaccine delivery strategies, appropriate communication strategies and targeted advocacy strategies to introduce HPV vaccines in the Vietnamese context.
Hampson, Katie; Cleaveland, Sarah; Briggs, Deborah
Background Prompt post-exposure prophylaxis (PEP) is essential in preventing the fatal onset of disease in persons exposed to rabies. Unfortunately, life-saving rabies vaccines and biologicals are often neither accessible nor affordable, particularly to the poorest sectors of society who are most at risk and upon whom the largest burden of rabies falls. Increasing accessibility, reducing costs and preventing delays in delivery of PEP should therefore be prioritized. Methodology/Principal Findings We analyzed different PEP vaccination regimens and evaluated their relative costs and benefits to bite victims and healthcare providers. We found PEP vaccination to be an extremely cost-effective intervention (from $200 to less than $60/death averted). Switching from intramuscular (IM) administration of PEP to equally efficacious intradermal (ID) regimens was shown to result in significant savings in the volume of vaccine required to treat the same number of patients, which could mitigate vaccine shortages, and would dramatically reduce the costs of implementing PEP. We present financing mechanisms that would make PEP more affordable and accessible, could help subsidize the cost for those most in need, and could even support new and existing rabies control and prevention programs. Conclusions/Significance We conclude that a universal switch to ID delivery would improve the affordability and accessibility of PEP for bite victims, leading to a likely reduction in human rabies deaths, as well as being economical for healthcare providers. PMID:21408121
Full Text Available DNA, the essential part of the life is making way in to new vaccine technology. Plasmid vectors from the bacteria have revolutionized the world of vaccine design by its new technology DNA vaccines. Small portion of the nucleotides from the pathogen held under the control of promoter in a plasmid vector can be used as a vaccine. DNA vaccines alleviate the odds of the other vaccines by having good hold on both the faces of the immunity. The key to the success of DNA vaccine lies in the route of administration of the vaccine which can be done in many ways. Prime boost strategy is an approach used to boost the action of DNA vaccine. To date there are only four DNA vaccine available in the market. [Vet World 2013; 6(4.000: 228-232
Selmer, Jan; Leung, Alicia S.M.
Purpose - The purpose of this study is to explore coping strategies of female business expatriates and to examine how these strategies are associated with the women's international adjustment. Design/methodology/approach - Data were collected through mail surveys to Western female business...
Oyarzún, Patricio; Kobe, Bostjan
Novel vaccination approaches based on rational design of B- and T-cell epitopes - epitope-based vaccines - are making progress in the clinical trial pipeline. The epitope-focused recombinant protein-based malaria vaccine (termed RTS,S) is a next-generation approach that successfully reached phase-III trials, and will potentially become the first commercial vaccine against a human parasitic disease. Progress made on methods such as recombinant DNA technology, advanced cell-culture techniques, immunoinformatics and rational design of immunogens are driving the development of these novel concepts. Synthetic recombinant proteins comprising both B- and T-cell epitopes can be efficiently produced through modern biotechnology and bioprocessing methods, and can enable the induction of large repertoires of immune specificities. In particular, the inclusion of appropriate CD4+ T-cell epitopes is increasingly considered a key vaccine component to elicit robust immune responses, as suggested by results coming from HIV-1 clinical trials. In silico strategies for vaccine design are under active development to address genetic variation in pathogens and several broadly protective "universal" influenza and HIV-1 vaccines are currently at different stages of clinical trials. Other methods focus on improving population coverage in target populations by rationally considering specificity and prevalence of the HLA proteins, though a proof-of-concept in humans has not been demonstrated yet. Overall, we expect immunoinformatics and bioprocessing methods to become a central part of the next-generation epitope-based vaccine development and production process.
Bhat-Schelbert, Kavitha; Lin, Chyongchiou Jeng; Matambanadzo, Annamore; Hannibal, Kristin; Nowalk, Mary Patricia; Zimmerman, Richard K
The CDC recommends annual influenza vaccination for all children age 6 months and older, yet vaccination rates remain modest. Effective strategies to improve influenza vaccination for children are needed. Eight focus groups with 91 parents, teens, pediatric healthcare staff and providers, and immunization and marketing experts were conducted, audiotaped, transcribed verbatim, and coded based on grounded theory. Three themes emerged: barriers, facilitators, and strategies. Barriers included fear, misinformation, and mistrust, with exacerbation of these barriers attributed to media messages. Many considered influenza vaccination unnecessary and inconvenient, but would accept vaccination if recipients or other family members were considered high risk, if recommended by their doctor or another trusted person, or if offered or mandated by the school. Access to better information regarding influenza disease burden and vaccine safety and efficacy were notable facilitators, as were prevention of the inconvenience of missing work or important events, and if the child requests to receive the vaccine. Marketing strategies included incentives, jingles, videos, wearable items, strategically-located information sheets or posters, and promotion by informed counselors. Practice-based strategies included staff buy-in, standing orders protocols, vaccination clinics, and educational videos. Teen-specific strategies included message delivery through schools, texting, internet, and social networking sites. To improve influenza vaccination rates for children using practice-based interventions, participants suggested campaigns that provide better information regarding the vaccine, the disease and its implications, and convenient access to vaccination. Strategies targeting adolescents should use web-based social marketing technologies and campaigns based in schools. Copyright Â© 2012 Elsevier Ltd. All rights reserved.
Gruijl, de Tanja; Eertwegh, van den Alfons; Pinedo, Herbert; Scheper, Rik
The Weld of tumor vaccination is currently undergoing a shift in focus, from individualized tailor-made vaccines to more generally applicable vaccine formulations. Although primarily predicated by Wnancial and logistic considerations, stemming from a growing awareness that clinical development
Smith, Todd G; Millien, Max; Vos, Ad; Fracciterne, Franso A; Crowdis, Kelly; Chirodea, Cornelius; Medley, Alexandra; Chipman, Richard; Qin, Yunlong; Blanton, Jesse; Wallace, Ryan
During the 20th century parenteral vaccination of dogs at central-point locations was the foundation of successful canine rabies elimination programs in numerous countries. However, countries that remain enzootic for canine rabies have lower infrastructural development compared to countries that have achieved elimination, which may make traditional vaccination methods less successful. Alternative vaccination methods for dogs must be considered, such as oral rabies vaccine (ORV). In 2016, a traditional mass dog vaccination campaign in Haiti was supplemented with ORV to improve vaccination coverage and to evaluate the use of ORV in dogs. Blisters containing live-attenuated, vaccine strain SPBNGAS-GAS were placed in intestine bait and distributed to dogs by hand. Serum was collected from 107 dogs, aged 3-12 months with no reported prior rabies vaccination, pre-vaccination and from 78/107 dogs (72.9%) 17 days post-vaccination. The rapid florescent focus inhibition test (RFFIT) was used to detect neutralizing antibodies and an ELISA to detect rabies binding antibodies. Post-vaccination, 38/41 (92.7%) dogs that received parenteral vaccine had detectable antibody (RFFIT >0.05 IU/mL), compared to 16/27 (59.3%, p 40% blocking, p 0.05 IU/mL) were detected in 10/107 reportedly vaccine-naïve dogs (9.3%). Parenteral vaccination remains the most reliable method for ensuring adequate immune response in dogs, however ORV represents a viable strategy to supplement existing parental vaccination campaigns in hard-to-reach dog populations. The hand-out model reduces the risk of unintended contact with ORV through minimizing vaccine blisters left in the community. Published by Elsevier Ltd.
Alam, Md Jibran; Ashraf, Kutub Uddin Muhammad
Australian Box Jellyfish (C. fleckeri) has the most rapid acting venom known to in the arena of toxicological research and is capable enough of killing a person in less than 5 minutes inflicting painful, debilitating and potentially life-threatening stings in humans. It has been understood that C. fleckeri venom proteins CfTX-1, 2 and HSP70-1 contain cardiotoxic, neurotoxic and highly dermatonecrotic components that can cause itchy bumpy rash and cardiac arrest. As there is no effective drug available, novel approaches regarding epitope prediction for vaccine development were performed in this study. Peptide fragments as nonamers of these antigenic venom proteins were analyzed by using computational tools that would elicit humoral and cell mediated immunity, were focused for attempting vaccine design. By ranking the peptides according to their proteasomal cleavage sites, TAP scores and IC50<250 nM, the predictions were scrutinized. Furthermore, the epitope sequences were examined by in silico docking simulation with different specific HLA receptors. Interestingly, to our knowledge, this is the maiden hypothetical immunization that predicts the promiscuous epitopes with potential contributions to the tailored design of improved safe and effective vaccines against antigenic venom proteins of C. fleckeri which would be effective especially for the Australian population. Although the computational approaches executed here are based on concrete confidence which demands more validation and in vivo experiments to validate such in silico approach.
Aujo, Judith Caroline; Bakeera-Kitaka, Sabrina; Kiguli, Sarah; Mirembe, Florence
Vaccination against Human Papilloma Virus (HPV) before sexual debut has been recommended by WHO as a primary prevention strategy against cervical cancer. In Uganda, vaccination against HPV started as a demonstration project among young girls in Nakasongola; and Ibanda districts. Studies have suggested that vaccination against HPV could result in risky sexual behavior and increase the risk of early sexual debut.This study was done to compare the sexual behavior of HPV vaccinated and non vaccinated adolescent girls in two neighboring districts in Uganda; and to assess whether HPV vaccination had any influence on sexual behavior of vaccinated adolescent girls. This was an unmatched comparative study, which used both qualitative and quantitative study methods. It was carried out among 400 primary school girls aged 12 to 15 years in the districts of Nakasongola (vaccinated) and Luwero (non vaccinated). Quantitative data was collected using a questionnaire while qualitative data was obtained using focus group discussions and key informant interviews. The main outcome measure was the number of sexually active girls in each group. Of the 400 girls, 8 volunteered information that they were sexually active, 5(2.5%) from Luwero (non vaccinated) and 3 (1.5%) from Nakasongola (vaccinated), but there was no statistically significant difference between the 2 groups. HPV vaccination was not significantly associated with being sexually active. There was no significant difference in sexual behavior between vaccinated and non vaccinated girls.
Petrova, Dafina; Brunton, Carol Gray; Jaeger, Moritz; Lenneis, Anita; Munoz, Rocio; Garcia-Retamero, Rocio; Todorova, Irina
The Human Papilloma Virus (HPV) is the most common sexually transmitted infection (STI) and can cause cervical cancer. Two vaccines are available to protect against the most common strands of the virus. Vaccination programs differ across Europe but most neglect young adults, who are the group with the highest risk of contracting STIs. Our aim was to explore the views of young women from four European countries—Scotland, Spain, Serbia, and Bulgaria - about the HPV vaccine communication strategy. These countries are characterized by different cervical cancer prevalence and vaccine implementation policies. We conducted focus group discussions with young women (aged 18-26) with various vaccination histories in a purposive sample. We subjected the data to thematic analysis with the purpose of identifying themes related to communication about the HPV vaccine. We recorded the information sources mentioned by participants. Participants discussed numerous sources of vaccine-related information. They approached information critically rather than naively and questioned the sources' trustworthiness and motives. Participants desired transparent information about the risks of the virus and the risks and benefits of the vaccine. These risks and benefits were individualized in view of personal and external factors. Particular aspects of the vaccine and the way information was communicated resulted in feelings of uncertainty. There were notable cross-cultural differences in experiences with HPV vaccine communication. Our results suggest that transparent risk communication about the HPV vaccine is valued by young women. In addition, both individual and culturally-dependent factors influenced experiences with, and preference for information.
He, Yongqun; Xiang, Zuoshuang
In vaccine design, databases and in silico tools play different but complementary roles. Databases collect experimentally verified vaccines and vaccine components, and in silico tools provide computational methods to predict and design new vaccines and vaccine components. Vaccine-related databases include databases of vaccines and vaccine components. In the USA, the Food and Drug Administration (FDA) maintains a database of licensed human vaccines, and the US Department of Agriculture keeps a database of licensed animal vaccines. Databases of vaccine clinical trials and vaccines in research also exist. The important vaccine components include vaccine antigens, vaccine adjuvants, vaccine vectors, and -vaccine preservatives. The vaccine antigens can be whole proteins or immune epitopes. Various in silico vaccine design tools are also available. The Vaccine Investigation and Online Information Network (VIOLIN; http://www.violinet.org ) is a comprehensive vaccine database and analysis system. The VIOLIN database includes various types of vaccines and vaccine components. VIOLIN also includes Vaxign, a Web-based in silico vaccine design program based on the reverse vaccinology strategy. Vaccine information and resources can be integrated with Vaccine Ontology (VO). This chapter introduces databases and in silico tools that facilitate vaccine design, especially those in the VIOLIN system.
"Over the last three decades, researchers have made remarkable progress in creating and testing family-focused programs aimed at fostering the cognitive, affective, and behavioral health of children...
Full Text Available To effectively and efficiently reduce the morbidity and mortality that may be caused by outbreaks of emerging infectious diseases, it is very important for public health agencies to make informed decisions for controlling the spread of the disease. Such decisions must incorporate various kinds of intervention strategies, such as vaccinations, school closures and border restrictions. Recently, researchers have paid increased attention to searching for effective vaccine distribution strategies for reducing the effects of pandemic outbreaks when resources are limited. Most of the existing research work has been focused on how to design an effective age-structured epidemic model and to select a suitable vaccine distribution strategy to prevent the propagation of an infectious virus. Models that evaluate age structure effects are common, but models that additionally evaluate geographical effects are less common. In this paper, we propose a new SEIR (susceptible-exposed-infectious šC recovered model, named the hybrid SEIR-V model (HSEIR-V, which considers not only the dynamics of infection prevalence in several age-specific host populations, but also seeks to characterize the dynamics by which a virus spreads in various geographic districts. Several vaccination strategies such as different kinds of vaccine coverage, different vaccine releasing times and different vaccine deployment methods are incorporated into the HSEIR-V compartmental model. We also design four hybrid vaccination distribution strategies (based on