A Systems Approach to Vaccine Decision Making

PubMed Central

Lee, Bruce Y.; Mueller, Leslie E.; Tilchin, Carla G.

2016-01-01

Vaccines reside in a complex multiscale system that includes biological, clinical, behavioral, social, operational, environmental, and economical relationships. Not accounting for these systems when making decisions about vaccines can result in changes that have little effect rather than solutions, lead to unsustainable solutions, miss indirect (e.g., secondary, tertiary, and beyond) effects, cause unintended consequences, and lead to wasted time, effort, and resources. Mathematical and computational modeling can help better understand and address complex systems by representing all or most of the components, relationships, and processes. Such models can serve as “virtual laboratories” to examine how a system operates and test the effects of different changes within the system. Here are ten lessons learned from using computational models to bring more of a systems approach to vaccine decision making: (i) traditional single measure approaches may overlook opportunities; (ii) there is complex interplay among many vaccine, population, and disease characteristics; (iii) accounting for perspective can identify synergies; (iv) the distribution system should not be overlooked; (v) target population choice can have secondary and tertiary effects; (vi) potentially overlooked characteristics can be important; (vii) characteristics of one vaccine can affect other vaccines; (viii) the broader impact of vaccines is complex; (ix) vaccine administration extends beyond the provider level; (x) and the value of vaccines is dynamic. PMID:28017430

A systems approach to vaccine decision making.

PubMed

Lee, Bruce Y; Mueller, Leslie E; Tilchin, Carla G

2017-01-20

Vaccines reside in a complex multiscale system that includes biological, clinical, behavioral, social, operational, environmental, and economical relationships. Not accounting for these systems when making decisions about vaccines can result in changes that have little effect rather than solutions, lead to unsustainable solutions, miss indirect (e.g., secondary, tertiary, and beyond) effects, cause unintended consequences, and lead to wasted time, effort, and resources. Mathematical and computational modeling can help better understand and address complex systems by representing all or most of the components, relationships, and processes. Such models can serve as "virtual laboratories" to examine how a system operates and test the effects of different changes within the system. Here are ten lessons learned from using computational models to bring more of a systems approach to vaccine decision making: (i) traditional single measure approaches may overlook opportunities; (ii) there is complex interplay among many vaccine, population, and disease characteristics; (iii) accounting for perspective can identify synergies; (iv) the distribution system should not be overlooked; (v) target population choice can have secondary and tertiary effects; (vi) potentially overlooked characteristics can be important; (vii) characteristics of one vaccine can affect other vaccines; (viii) the broader impact of vaccines is complex; (ix) vaccine administration extends beyond the provider level; and (x) the value of vaccines is dynamic. Copyright © 2016 Elsevier Ltd. All rights reserved.

Recent developments in leishmaniasis vaccine delivery systems.

PubMed

Bhowmick, Sudipta; Ali, Nahid

2008-07-01

The observation that recovery from infection with Leishmania confers immunity to reinfection suggests that control of leishmaniasis by vaccination may be possible. New generation vaccines, particularly those based on recombinant proteins and DNA, are found to be less immunogenic. There is an urgent need for the development of new and improved vaccine adjuvants. Based on their principal mechanisms of action, adjuvants can be broadly separated into two classes: immunostimulatory adjuvants and vaccine delivery systems. Vaccine delivery systems can carry both antigen and adjuvant for effective delivery to the antigen-presenting cells (APCs). In this article, we review the adjuvants, the delivery systems and their combinations used in the search of an effective vaccine against leishmaniasis. Based on current knowledge, cationic liposomes appear to have better prospects as effective delivery systems for developing a vaccine for leishmaniasis.

Systems vaccinology: probing humanity's diverse immune systems with vaccines.

PubMed

Pulendran, Bali

2014-08-26

Homo sapiens are genetically diverse, but dramatic demographic and socioeconomic changes during the past century have created further diversification with respect to age, nutritional status, and the incidence of associated chronic inflammatory disorders and chronic infections. These shifting demographics pose new challenges for vaccination, as emerging evidence suggests that age, the metabolic state, and chronic infections can exert major influences on the immune system. Thus, a key public health challenge is learning how to reprogram suboptimal immune systems to induce effective vaccine immunity. Recent advances have applied systems biological analysis to define molecular signatures induced early after vaccination that correlate with and predict the later adaptive immune responses in humans. Such "systems vaccinology" approaches offer an integrated picture of the molecular networks driving vaccine immunity, and are beginning to yield novel insights about the immune system. Here we discuss the promise of systems vaccinology in probing humanity's diverse immune systems, and in delineating the impact of genes, the environment, and the microbiome on protective immunity induced by vaccination. Such insights will be critical in reengineering suboptimal immune systems in immunocompromised populations.

Guidelines for maintaining and managing the vaccine cold chain.

PubMed

2003-10-24

In February 2002, the Advisory Committee on Immunization Practices (ACIP) and American Academy of Family Physicians (AAFP) released their revised General Recommendations on Immunization, which included recommendations on the storage and handling of immunobiologics. Because of increased concern over the potential for errors with the vaccine cold chain (i.e., maintaining proper vaccine temperatures during storage and handling to preserve potency), this notice advises vaccine providers of the importance of proper cold chain management practices. This report describes proper storage units and storage temperatures, outlines appropriate temperature-monitoring practices, and recommends steps for evaluating a temperature-monitoring program. The success of efforts against vaccine-preventable diseases is attributable in part to proper storage and handling of vaccines. Exposure of vaccines to temperatures outside the recommended ranges can affect potency adversely, thereby reducing protection from vaccine-preventable diseases. Good practices to maintain proper vaccine storage and handling can ensure that the full benefit of immunization is realized.

Methodology for the assessment of brucellosis management practices and its vaccination campaign: example in two Argentine districts.

PubMed

Aznar, M N; Arregui, M; Humblet, M F; Samartino, L E; Saegerman, C

2017-09-07

In Argentina, vaccination with Brucella abortus Strain 19 vaccine is mandatory. The objective of the study was to develop and test a method for evaluating, in an innovative way, some farmers' and veterinarians' management practices in relation to brucellosis and to assess the vaccination campaign and coverage. The work took place in Brandsen and Navarro districts. Four questionnaires were designed (for officials from Local Sanitary Entities, vaccinators, vet practitioners and farmers). Responses were coded as "ideal" (0) and "not ideal" (1). To assess the relative weight of each question ("item"), experts ranked the items according to their impact on management practices and vaccination. A weighted score was then calculated. A higher weighted score was assigned to the worse practices. Farmers obtaining a global weighted score above the third quartile were classified as "inappropriately managed farms", to be compared per type of production system and district. To assess the immunization coverage, female calves were sampled 30 to 50 days post vaccination; they were expected to react positively to serological diagnostic tests (DT+). There were significantly more inappropriately managed farms and higher global scores among beef farmers and in Brandsen. Eighty three percent (83%) of female calves were DT+, significantly under the ideal immunization coverage (95%). Only 48% of farms were considered well vaccinated. DT+ results were positively associated with the Brandsen district (OR = 25.94 [4.60-1146.21] and with the farms having more than 200 cow heads ((OR = 78.34 [4.09-1500.00]). On the contrary, DT+ were less associated with vaccinators being veterinary practitioners (OR = 0.07 [0.006-0.78]). Farmers are well advised by their veterinary practitioners but they should improve some management practices. The vaccination campaign is globally well implemented, but the immunization coverage and some vaccinators' practices should be improved. This study leads to a

Vaccine cold chain: Part 2. Training personnel and program management.

PubMed

Rogers, Bonnie; Dennison, Kim; Adepoju, Nikki; Dowd, Shelia; Uedoi, Kenneth

2010-09-01

The Centers for Disease Control and Prevention reports that professionals in clinic settings may not be adequately storing and handling vaccine, leading to insufficient immunity of vaccinated individuals. Part 2 of this article provides information about the importance of adequate personnel training and program management policies and procedures needed to implement and maintain an effective vaccine cold chain program. Copyright 2010, SLACK Incorporated.

Macromolecular systems for vaccine delivery.

PubMed

MuŽíková, G; Laga, R

2016-10-20

Vaccines have helped considerably in eliminating some life-threatening infectious diseases in past two hundred years. Recently, human medicine has focused on vaccination against some of the world's most common infectious diseases (AIDS, malaria, tuberculosis, etc.), and vaccination is also gaining popularity in the treatment of cancer or autoimmune diseases. The major limitation of current vaccines lies in their poor ability to generate a sufficient level of protective antibodies and T cell responses against diseases such as HIV, malaria, tuberculosis and cancers. Among the promising vaccination systems that could improve the potency of weakly immunogenic vaccines belong macromolecular carriers (water soluble polymers, polymer particels, micelles, gels etc.) conjugated with antigens and immunistumulatory molecules. The size, architecture, and the composition of the high molecular-weight carrier can significantly improve the vaccine efficiency. This review includes the most recently developed (bio)polymer-based vaccines reported in the literature.

Vaccine allergy.

PubMed

Caubet, Jean-Christoph; Ponvert, Claude

2014-08-01

Overdiagnosis of vaccine allergy is considered a major public health problem. This article discusses the different types of allergic reactions after immunization based on the timing (immediate vs nonimmediate) and the extent of the reaction (local vs systemic). The vaccine components potentially responsible for an allergic reaction are discussed, as well as the management of patients with a history of reaction to a specific vaccine and those with a history of allergy to one of the vaccine components. Copyright © 2014 Elsevier Inc. All rights reserved.

Immunisation Information Systems – useful tools for monitoring vaccination programmes in EU/EEA countries, 2016

PubMed Central

Derrough, Tarik; Olsson, Kate; Gianfredi, Vincenza; Simondon, Francois; Heijbel, Harald; Danielsson, Niklas; Kramarz, Piotr; Pastore-Celentano, Lucia

2017-01-01

Immunisation Information Systems (IIS) are computerised confidential population based-systems containing individual-level information on vaccines received in a given area. They benefit individuals directly by ensuring vaccination according to the schedule and they provide information to vaccine providers and public health authorities responsible for the delivery and monitoring of an immunisation programme. In 2016, the European Centre for Disease Prevention and Control (ECDC) conducted a survey on the level of implementation and functionalities of IIS in 30 European Union/European Economic Area (EU/EEA) countries. It explored the governance and financial support for the systems, IIS software, system characteristics in terms of population, identification of immunisation recipients, vaccinations received, and integration with other health record systems, the use of the systems for surveillance and programme management as well as the challenges involved with implementation. The survey was answered by 27 of the 30 EU/EEA countries having either a system in production at national or subnational levels (n = 16), or being piloted (n = 5) or with plans for setting up a system in the future (n = 6). The results demonstrate the added-value of IIS in a number of areas of vaccination programme monitoring such as monitoring vaccine coverage at local geographical levels, linking individual immunisation history with health outcome data for safety investigations, monitoring vaccine effectiveness and failures and as an educational tool for both vaccine providers and vaccine recipients. IIS represent a significant way forward for life-long vaccination programme monitoring. PMID:28488999

Weakened Immune System and Adult Vaccination

MedlinePlus

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

Succeeding in New Vaccine Introduction: Lessons Learned From the Introduction of Inactivated Poliovirus Vaccine in Cameroon, Kenya, and Nigeria

PubMed Central

Snidal, Sarah; Saidu, Yauba; Ojumu, Abiola; Ngatia, Antony; Bagana, Murtala; Mutuku, Faith; Sobngwi, Joelle; Efe-Aluta, Oniovo; Roper, Julia; LeTallec, Yann; Kang’ethe, Alice

2017-01-01

Abstract Introducing a new vaccine is a large-scale endeavor that can face many challenges, resulting in introduction delays and inefficiencies. The development of national task teams and tools, such as prelaunch trackers, for the introduction of new vaccines (hereafter, “new vaccine introductions” [NVIs]) can help countries implement robust project management systems, front-load critical preparatory activities, and ensure continuous communication around vaccine supply and financing. In addition, implementing postlaunch assessments to take rapid corrective action accelerates the uptake of the new vaccines. NVIs can provide an opportunity to strengthen routine immunization, through strengthening program management systems or by reinforcing local immunization managers’ abilities, among others. This article highlights key lessons learned during the introduction of inactivated poliovirus vaccine in 3 countries that would make future NVIs more successful. The article concludes by considering how the Immunization Systems Management Group of the Global Polio Eradication Initiative has been useful to the NVI process and how such global structures could be further enhanced. PMID:28838156

Perspectives of Immunization Program Managers on 2009-10 H1N1 Vaccination in the United States: A National Survey

PubMed Central

Seib, Katherine; Wells, Katelyn; Hannan, Claire; Orenstein, Walter A.; Whitney, Ellen A. S.; Hinman, Alan R.; Berkelman, Ruth L.; Omer, Saad B.

2012-01-01

Abstract In June and July 2010, we conducted a national internet-based survey of 64 city, state, and territorial immunization program managers (IPMs) to assess their experiences in managing the 2009-10 H1N1 influenza vaccination campaign. Fifty-four (84%) of the managers or individuals responsible for an immunization program responded to the survey. To manage the campaign, 76% indicated their health department activated an incident command system (ICS) and 49% used an emergency operations center (EOC). Forty percent indicated they shared the leadership of the campaign with their state-level emergency preparedness program. The managers' perceptions of the helpfulness of the emergency preparedness staff was higher when they had collaborated with the emergency preparedness program on actual or simulated mass vaccination events within the previous 2 years. Fifty-seven percent found their pandemic influenza plan helpful, and those programs that mandated that vaccine providers enter data into their jurisdiction's immunization information system (IIS) were more likely than those who did not mandate data entry to rate their IIS as valuable for facilitating registration of nontraditional providers (42% vs. 25%, p<0.05) and tracking recalled influenza vaccine (50% vs. 38%, p<0.05). Results suggest that ICS and EOC structures, pandemic influenza plans, collaborations with emergency preparedness partners during nonemergencies, and expanded use of IIS can enhance immunization programs' ability to successfully manage a large-scale vaccination campaign. Maintaining the close working relationships developed between state-level immunization and emergency preparedness programs during the H1N1 influenza vaccination campaign will be especially important as states prepare for budget cuts in the coming years. PMID:22360580

Systems Vaccinology: Enabling rational vaccine design with systems biological approaches

PubMed Central

Hagan, Thomas; Nakaya, Helder I.; Subramaniam, Shankar; Pulendran, Bali

2015-01-01

Vaccines have drastically reduced the mortality and morbidity of many diseases. However, vaccines have historically been developed empirically, and recent development of vaccines against current pandemics such as HIV and malaria has been met with difficulty. The advent of high-throughput technologies, coupled with systems biological methods of data analysis, has enabled researchers to interrogate the entire complement of a variety of molecular components within cells, and characterize the myriad interactions among them in order to model and understand the behavior of the system as a whole. In the context of vaccinology, these tools permit exploration of the molecular mechanisms by which vaccines induce protective immune responses. Here we review the recent advances, challenges, and potential of systems biological approaches in vaccinology. If the challenges facing this developing field can be overcome, systems vaccinology promises to empower the identification of early predictive signatures of vaccine response, as well as novel and robust correlates of protection from infection. Such discoveries, along with the improved understanding of immune responses to vaccination they impart, will play an instrumental role in development of the next generation of rationally designed vaccines. PMID:25858860

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

PubMed

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

2012-02-01

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

Recent trends in vaccine delivery systems: A review

PubMed Central

Saroja, CH; Lakshmi, PK; Bhaskaran, Shyamala

2011-01-01

Vaccines are the preparations given to patients to evoke immune responses leading to the production of antibodies (humoral) or cell-mediated responses that will combat infectious agents or noninfectious conditions such as malignancies. Alarming safety profile of live vaccines, weak immunogenicity of sub-unit vaccines and immunization, failure due to poor patient compliance to booster doses which should potentiate prime doses are few strong reasons, which necessitated the development of new generation of prophylactic and therapeutic vaccines to promote effective immunization. Attempts are being made to deliver vaccines through carriers as they control the spatial and temporal presentation of antigens to immune system thus leading to their sustained release and targeting. Hence, lower doses of weak immunogens can be effectively directed to stimulate immune responses and eliminate the need for the administration of prime and booster doses as a part of conventional vaccination regimen. This paper reviews carrier systems such as liposomes, microspheres, nanoparticles, dendrimers, micellar systems, ISCOMs, plant-derived viruses which are now being investigated and developed as vaccine delivery systems. This paper also describes various aspects of “needle-free technologies” used to administer the vaccine delivery systems through different routes into the human body. PMID:23071924

Systems vaccinology: Probing humanity’s diverse immune systems with vaccines

PubMed Central

Pulendran, Bali

2014-01-01

Homo sapiens are genetically diverse, but dramatic demographic and socioeconomic changes during the past century have created further diversification with respect to age, nutritional status, and the incidence of associated chronic inflammatory disorders and chronic infections. These shifting demographics pose new challenges for vaccination, as emerging evidence suggests that age, the metabolic state, and chronic infections can exert major influences on the immune system. Thus, a key public health challenge is learning how to reprogram suboptimal immune systems to induce effective vaccine immunity. Recent advances have applied systems biological analysis to define molecular signatures induced early after vaccination that correlate with and predict the later adaptive immune responses in humans. Such “systems vaccinology” approaches offer an integrated picture of the molecular networks driving vaccine immunity, and are beginning to yield novel insights about the immune system. Here we discuss the promise of systems vaccinology in probing humanity’s diverse immune systems, and in delineating the impact of genes, the environment, and the microbiome on protective immunity induced by vaccination. Such insights will be critical in reengineering suboptimal immune systems in immunocompromised populations. PMID:25136102

The imperative for stronger vaccine supply and logistics systems.

PubMed

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

2013-04-18

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

Evaluation of a pilot intervention to redesign the decentralised vaccine supply chain system in Nigeria.

PubMed

Molemodile, Shola; Wotogbe, Maruchi; Abimbola, Seye

2017-05-01

Responsibility for immunisation in Nigeria is decentralised to sub-national governments. So far, they have failed to achieve optimal coverage for their populations. We evaluated a pilot intervention implemented between 2013 and 2014 to redesign a vaccine supply chain management system in Kano, Nigeria. The intervention included financing immunisation services from a designated pool of government and donor funds, a visibility tool to track vaccine stock, and a private vendor engaged to deliver vaccines directly to health facilities. The number of local government areas within the state with adequate vaccine stock increased from 21% to 98% after 10 months. To understand how the intervention achieved this outcome, we analysed immunisation coverage for the period and interviewed 18 respondents across different levels of government. We found that the intervention worked by improving ownership and accountability for immunisation by sub-national governments and their capacity for generating resources and management (of data and the supply chain). While the intervention focused on improving immunisation coverage, we identified gaps in the demand for services. Efforts to improve immunisation coverage and vaccine supply systems should streamline decentralised structures, empower sub-national governments with financial and technical capacity, and promote strategies to improve the demand and use of services.

Financing and systems barriers to seasonal influenza vaccine delivery in community settings.

PubMed

Penfold, Robert B; Rusinak, Donna; Lieu, Tracy A; Shefer, Abigail; Messonnier, Mark; Lee, Grace M

2011-12-06

Recommendations for annual seasonal influenza vaccination have expanded to now include >300 million children and adults each year. Community settings have become increasingly important venues for influenza vaccination. We sought to identify barriers to and solutions for expanding influenza vaccination in community settings. Semi-structured telephone interviews were conducted from 01/09 to 06/10 with a range of stakeholders involved in influenza vaccination, including health plans, medical services firms, retail based clinics, pharmacies, schools, and state and local public health immunization programs. Participants (n=65) were asked about barriers and feasible solutions to influenza vaccine delivery to children and adults in community settings. Key themes were identified through iterative coding using a grounded theory approach. Stakeholders identified specific financial barriers to influenza vaccine delivery in 3 major areas: purchase and distribution, delivery, and reimbursement. Limited purchasing power, the uncertain nature of public demand, and unpredictable timing of influenza vaccine supply were important barriers to enhance delivery in community settings. Barriers to delivery included complexities in running off-site clinics, especially in school settings, the need to manage publicly vs. privately purchased vaccines separately, and state-to-state variability in requirements for credentialing, physician oversight, and reporting. Reimbursement barriers included a protracted credentialing process, the need to determine insurance eligibility at point-of-service, and lack of a billing infrastructure in off-site clinics. Opportunities to mitigate financial barriers to influenza vaccine delivery in community settings focused on coordination across providers and the role of public health as a "trusted broker" to overcome existing challenges. Financial and systems barriers hamper the optimal use of community settings to effectively deliver influenza vaccines. Public

Lessons Learned From Managing the Planning and Implementation of Inactivated Polio Vaccine Introduction in Support of the Polio Endgame.

PubMed

Zipursky, Simona; Patel, Manish; Farrell, Margaret; Gonzalez, Alejandro Ramirez; Kachra, Tasleem; Folly, Yann; Kurji, Feyrouz; Veira, Chantal Laroche; Wootton, Emily; Hampton, Lee M

2017-07-01

The Immunization Systems Management Group (IMG) was established as a time-limited entity, responsible for the management and coordination of Objective 2 of the Polio Eradication and Endgame Strategic Plan. This objective called for the introduction of at least 1 dose of inactivated polio vaccine (IPV) into the routine immunization programs of all countries using oral polio vaccine (OPV) only. Despite global vaccine shortages, which limited countries' abilities to access IPV in a timely manner, 105 of 126 countries using OPV only introduced IPV within a 2.5-year period, making it the fastest rollout of a new vaccine in history. This achievement can be attributed to several factors, including the coordination work of the IMG; high-level engagement and advocacy across partners; the strong foundations of the Expanded Programme on Immunization at all levels; Gavi, the Vaccine Alliance's vaccine introduction experiences and mechanisms; innovative approaches; and proactive communications. In many ways, the IMG's work on IPV introduction can serve as a model for other vaccine introductions, especially in an accelerated context. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Protocol for a randomised controlled trial examining the impact of a web-based personally controlled health management system on the uptake of influenza vaccination rates.

PubMed

Lau, Annie Y S; Sintchenko, Vitali; Crimmins, Jacinta; Magrabi, Farah; Gallego, Blanca; Coiera, Enrico

2012-04-02

Online social networking and personally controlled health management systems (PCHMS) offer a new opportunity for developing innovative interventions to prevent diseases of public health concern (e.g., influenza) but there are few comparative studies about patterns of use and impact of these systems. A 2010 CONSORT-compliant randomised controlled trial with a two-group parallel design will assess the efficacy of a web-based PCHMS called Healthy.me in facilitating the uptake of influenza vaccine amongst university students and staff. Eligible participants are randomised either to obtain access to Healthy.me or a 6-month waitlist. Participants complete pre-study, post-study and monthly surveys about their health and utilisation of health services. A post-study clinical audit will be conducted to validate self-reports about influenza vaccination and visits to the university health service due to influenza-like illness (ILI) amongst a subset of participants. 600 participants older than 18 years with monthly access to the Internet and email will be recruited. Participants who (i) discontinue the online registration process; (ii) report obtaining an influenza vaccination in 2010 before the commencement of the study; or (iii) report being influenced by other participants to undertake influenza vaccination will be excluded from analysis. The primary outcome measure is the number of participants obtaining influenza vaccination during the study. Secondary outcome measures include: number of participants (i) experiencing ILI symptoms, (ii) absent from or experiencing impairment in work or study due to ILI symptoms, (iii) using health services or medications due to ILI symptoms; (iv) expressing positive or negative attitudes or experiences towards influenza vaccination, via their reasons of receiving (or not receiving) influenza vaccine; and (v) their patterns of usage of Healthy.me (e.g., frequency and timing of hits, duration of access, uptake of specific functions). This

Protocol for a randomised controlled trial examining the impact of a web-based personally controlled health management system on the uptake of influenza vaccination rates

PubMed Central

2012-01-01

Background Online social networking and personally controlled health management systems (PCHMS) offer a new opportunity for developing innovative interventions to prevent diseases of public health concern (e.g., influenza) but there are few comparative studies about patterns of use and impact of these systems. Methods/Design A 2010 CONSORT-compliant randomised controlled trial with a two-group parallel design will assess the efficacy of a web-based PCHMS called Healthy.me in facilitating the uptake of influenza vaccine amongst university students and staff. Eligible participants are randomised either to obtain access to Healthy.me or a 6-month waitlist. Participants complete pre-study, post-study and monthly surveys about their health and utilisation of health services. A post-study clinical audit will be conducted to validate self-reports about influenza vaccination and visits to the university health service due to influenza-like illness (ILI) amongst a subset of participants. 600 participants older than 18 years with monthly access to the Internet and email will be recruited. Participants who (i) discontinue the online registration process; (ii) report obtaining an influenza vaccination in 2010 before the commencement of the study; or (iii) report being influenced by other participants to undertake influenza vaccination will be excluded from analysis. The primary outcome measure is the number of participants obtaining influenza vaccination during the study. Secondary outcome measures include: number of participants (i) experiencing ILI symptoms, (ii) absent from or experiencing impairment in work or study due to ILI symptoms, (iii) using health services or medications due to ILI symptoms; (iv) expressing positive or negative attitudes or experiences towards influenza vaccination, via their reasons of receiving (or not receiving) influenza vaccine; and (v) their patterns of usage of Healthy.me (e.g., frequency and timing of hits, duration of access, uptake of

Particulate delivery systems for biodefense subunit vaccines.

PubMed

Bramwell, Vincent W; Eyles, Jim E; Oya Alpar, H

2005-06-17

Expanding identification of potentially protective subunit antigens and correlates of protection has provided a basis for the introduction of safer vaccines. Despite encouraging results in animal models, the significant potential of particulate delivery systems in vaccine design has not yet translated into effective vaccines available for use in humans. This review article will focus on the current status of the development of particulate vaccines, mainly liposomes and bio-degradable polymers, against potential agents for biowarfare: plague, anthrax, botulinum, and smallpox; and filoviruses: Marburg and Ebola.

Tennessee’s 3-Star Report: Using Available Data Systems to Reduce Missed Opportunities to Vaccinate Preteens

PubMed Central

Moore, Kelly L.; Fankhauser, Melissa K.; Hull, Pamela C.

2016-01-01

All preteens should receive tetanus–diphtheria–pertussis vaccine (Tdap), quadrivalent meningococcal vaccine (Men-ACWY), and the human papillomavirus (HPV) cancer vaccine series. In Tennessee, HPV vaccination rates have stagnated at low levels for a decade. Three fundamental strategies to reduce missed opportunities for immunization include administering all recommended vaccines at the same visit, making strong recommendations for vaccines, and auditing and feedback. In Tennessee, during each summer, a surge of preteens visit local health departments (LHDs) to receive a required Tdap vaccine before entering seventh grade, presenting an opportunity to administer Men-ACWY and HPV. The Tennessee Immunization Program (TIP) coined the term “3-Star visit” for such encounters and developed a monthly report to track them using data from the Patient Tracking Billing Management Information System (PTBMIS) used by LHDs across Tennessee. Implementation of this quality improvement report has correlated with a substantial increase in 3-Star visits from 2013 to 2016, particularly during the summer months. PMID:27980415

Adverse events after anthrax vaccination reported to the Vaccine Adverse Event Reporting System (VAERS), 1990-2007.

PubMed

Niu, Manette T; Ball, Robert; Woo, Emily Jane; Burwen, Dale R; Knippen, Maureen; Braun, M Miles

2009-01-07

During the period March 1, 1998 to January 14, 2007, approximately 6 million doses of Anthrax vaccine adsorbed (AVA) vaccine were administered. As of January 16, 2007, 4753 reports of adverse events following receipt of AVA vaccination had been submitted to the Vaccine Adverse Event Reporting System (VAERS). Taken together, reports to VAERS did not definitively link any serious unexpected risk to this vaccine, and review of death and serious reports did not show a distinctive pattern indicative of a causal relationship to AVA vaccination. Continued monitoring of VAERS and analysis of potential associations between AVA vaccination and rare, serious events is warranted.

How a New Health Intervention Affects the Health Systems? Learnings from Pentavalent Vaccine Introduction in India.

PubMed

Lahariya, Chandrakant; Paruthi, Renu; Bhattacharya, Madhulekha

2016-04-01

To summarize the findings from a Post Introduction Evaluation (PIE) of pentavalent vaccine in Tamil Nadu and Kerala state of India and to understand how the health systems could be prepared for (prior to) introducing a new intervention and how such introduction could affect the health systems (afterwards). A post introduction evaluation (PIE) of Haemophilus influenzae type b (Hib) as pentavalent (DPT + HepB + Hib) vaccine was conducted in Tamil Nadu and Kerala states of India in July-Aug 2012. The PIE was conducted as per World Health Organization PIE methods and tools specifically adapted for India. This PIE adopted a 'mixed method approach' with qualitative data focus. The planning for the introduction of pentavalent vaccine provided opportunities to strengthen various functions of the health system i.e., piloting of Open Vial Policy, strengthening surveillance system, improving Adverse Events Following Immunization (AEFI) reporting system and formation of the technical expert groups. It provided opportunity for bringing attention on the immunization programme in general as well. After the vaccine introduction, the beneficial effects were noted on stewardship (increased oversight by top level policy makers and programme managers), creating resources (investment and trainings of staff in immunization), service delivery (increased coverage with the vaccines and improved quality of services) and financing (increased financial allocation and reduced out of pocket expenditures as more people started attending public health facilities). The vaccine introduction was found to be associated with improvement in the health equity, efficiency and service utilization (effective coverage). New vaccine introduction provides opportunities (both before and after) for strengthening the health systems in setting such as India. Preparing the health system for new challenges has potential to strengthen the health systems, if done in well-coordinated and planned manner. Considering

[Obligatory vaccination reporting in Saxony-Anhalt. Possibilities and limitations of establishing a computerized vaccination registry].

PubMed

Oppermann, H; Wahl, G; Borrmann, M; Fleischer, J

2009-11-01

Vaccination registries are databases intended to assess and manage complete vaccination data of as many individuals as possible in a population under survey. The task of these registries is to identify low vaccination rates on the individual and population level, to enable systems of reminding individuals, to focus vaccination campaigns and to maximize overall vaccination coverage. Saxony-Anhalt is the only federal state of Germany to have a law that prescribes the reporting of vaccinations. Vaccinations of children up to the age of 7 are reported to the regional public health services. However, as the law provides no regulations as to how the data should be registered and processed, the development of a vaccination registry depends entirely on the initiative and cooperation of the "players in vaccination". The key players in vaccination in Saxony-Anhalt have recently created a Vaccination-Committee, which set out to develop the theoretical standards and a software prototype for the establishment of a computerized vaccination registry. Recent developments in the public health reporting system of Saxony-Anhalt (which strives to modernize its computerized assessment of child and adolescent health) are now opening the possibility to integrate the vaccination registry into the commercially available child health software.

Managing the effect of TRIPS on availability of priority vaccines.

PubMed Central

Milstien, Julie; Kaddar, Miloud

2006-01-01

The stated purpose of intellectual property protection is to stimulate innovation. The Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS) requires all Members of the World Trade Organization (WTO) to enact national laws conferring minimum standards of intellectual property protection by certain deadlines. Critics of the Agreement fear that such action is inconsistent with ensuring access to medicines in the developing world. A WHO convened meeting on intellectual property rights and vaccines in developing countries, on which this paper is based, found no evidence that TRIPS has stimulated innovation in developing market vaccine development (where markets are weak) or that protection of intellectual property rights has had a negative effect on access to vaccines. However, access to future vaccines in the developing world could be threatened by compliance with TRIPS. The management of such threats requires adherence of all countries to the Doha Declaration on TRIPS, and the protections guaranteed by the Agreement itself, vigilance on TRIPS-plus elements of free trade agreements, developing frameworks for licensing and technology transfer, and promoting innovative vaccine development in developing countries. The role of international organizations in defining best practices, dissemination of information, and monitoring TRIPS impact will be crucial to ensuring optimal access to priority new vaccines for the developing world. PMID:16710544

The potential benefits of a new poliovirus vaccine for long-term poliovirus risk management.

PubMed

Duintjer Tebbens, Radboud J; Thompson, Kimberly M

2016-12-01

To estimate the incremental net benefits (INBs) of a hypothetical ideal vaccine with all of the advantages and no disadvantages of existing oral and inactivated poliovirus vaccines compared with current vaccines available for future outbreak response. INB estimates based on expected costs and polio cases from an existing global model of long-term poliovirus risk management. Excluding the development costs, an ideal poliovirus vaccine could offer expected INBs of US$1.6 billion. The ideal vaccine yields small benefits in most realizations of long-term risks, but great benefits in low-probability-high-consequence realizations. New poliovirus vaccines may offer valuable insurance against long-term poliovirus risks and new vaccine development efforts should continue as the world gathers more evidence about polio endgame risks.

Leishmaniasis: focus on the design of nanoparticulate vaccine delivery systems.

PubMed

Doroud, Delaram; Rafati, Sima

2012-01-01

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.

Vaccine safety monitoring systems in developing countries: an example of the Vietnam model.

PubMed

Ali, Mohammad; Rath, Barbara; Thiem, Vu Dinh

2015-01-01

Only few health intervention programs have been as successful as vaccination programs with respect to preventing morbidity and mortality in developing countries. However, the success of a vaccination program is threatened by rumors and misunderstanding about the risks of vaccines. It is short-sighted to plan the introduction of vaccines into developing countries unless effective vaccine safety monitoring systems are in place. Such systems that track adverse events following immunization (AEFI) is currently lacking in most developing countries. Therefore, any rumor may affect the entire vaccination program. Public health authorities should implement the safety monitoring system of vaccines, and disseminate safety issues in a proactive mode. Effective safety surveillance systems should allow for the conduct of both traditional and alternative epidemiologic studies through the use of prospective data sets. The vaccine safety data link implemented in Vietnam in mid-2002 indicates that it is feasible to establish a vaccine safety monitoring system for the communication of vaccine safety in developing countries. The data link provided the investigators an opportunity to evaluate AEFI related to measles vaccine. Implementing such vaccine safety monitoring system is useful in all developing countries. The system should be able to make objective and clear communication regarding safety issues of vaccines, and the data should be reported to the public on a regular basis for maintaining their confidence in vaccination programs.

Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS)

PubMed Central

Shimabukuro, Tom T.; Nguyen, Michael; Martin, David; DeStefano, Frank

2015-01-01

The Centers for Disease Control and Prevention (CDC) and the U.S. Food and Drug Administration (FDA) conduct post-licensure vaccine safety monitoring using the Vaccine Adverse Event Reporting System (VAERS), a spontaneous (or passive) reporting system. This means that after a vaccine is approved, CDC and FDA continue to monitor safety while it is distributed in the marketplace for use by collecting and analyzing spontaneous reports of adverse events that occur in persons following vaccination. Various methods and statistical techniques are used to analyze VAERS data, which CDC and FDA use to guide further safety evaluations and inform decisions around vaccine recommendations and regulatory action. VAERS data must be interpreted with caution due to the inherent limitations of passive surveillance. VAERS is primarily a safety signal detection and hypothesis generating system. Generally, VAERS data cannot be used to determine if a vaccine caused an adverse event. VAERS data interpreted alone or out of context can lead to erroneous conclusions about cause and effect as well as the risk of adverse events occurring following vaccination. CDC makes VAERS data available to the public and readily accessible online. We describe fundamental vaccine safety concepts, provide an overview of VAERS for healthcare professionals who provide vaccinations and might want to report or better understand a vaccine adverse event, and explain how CDC and FDA analyze VAERS data. We also describe strengths and limitations, and address common misconceptions about VAERS. Information in this review will be helpful for healthcare professionals counseling patients, parents, and others on vaccine safety and benefit-risk balance of vaccination. PMID:26209838

Emergency Preparedness in the Workplace: The Flulapalooza Model for Mass Vaccination

PubMed Central

Aliyu, Muktar H.; Byrne, Daniel W.; Qian, Keqin; McGown, Paula; Kinman, Patricia O.; Hanson, Katherine Louise; Culpepper, Demoyne; Cooley, Tamara J.; Yarbrough, Mary I.

2017-01-01

Objectives. To explore whether an emergency preparedness structure is a feasible, efficient, and sustainable way for health care organizations to manage mass vaccination events. Methods. We used the Hospital Incident Command System to conduct a 1-day annual mass influenza vaccination event at Vanderbilt University Medical Center over 5 successive years (2011–2015). Using continuous quality improvement principles, we assessed whether changes in layout, supply management, staffing, and documentation systems improved efficiency. Results. A total of 66 591 influenza vaccines were administered at 5 annual Flulapalooza events; 13 318 vaccines per event on average. Changes to the physical layout, staffing mix, and documentation processes improved vaccination efficiency 74%, from approximately 38 to 67 vaccines per hour per vaccinator, while reducing overall staffing needs by 38%. An unexpected finding was the role of social media in facilitating active engagement. Conclusions. Health care organizations can use a closed point-of-dispensing model and Hospital Incident Command System to conduct mass vaccination events, and can adopt the “Flulapalooza method” as a best practice model to enhance efficiency. PMID:28892449

Emergency Preparedness in the Workplace: The Flulapalooza Model for Mass Vaccination.

PubMed

Swift, Melanie D; Aliyu, Muktar H; Byrne, Daniel W; Qian, Keqin; McGown, Paula; Kinman, Patricia O; Hanson, Katherine Louise; Culpepper, Demoyne; Cooley, Tamara J; Yarbrough, Mary I

2017-09-01

To explore whether an emergency preparedness structure is a feasible, efficient, and sustainable way for health care organizations to manage mass vaccination events. We used the Hospital Incident Command System to conduct a 1-day annual mass influenza vaccination event at Vanderbilt University Medical Center over 5 successive years (2011-2015). Using continuous quality improvement principles, we assessed whether changes in layout, supply management, staffing, and documentation systems improved efficiency. A total of 66 591 influenza vaccines were administered at 5 annual Flulapalooza events; 13 318 vaccines per event on average. Changes to the physical layout, staffing mix, and documentation processes improved vaccination efficiency 74%, from approximately 38 to 67 vaccines per hour per vaccinator, while reducing overall staffing needs by 38%. An unexpected finding was the role of social media in facilitating active engagement. Health care organizations can use a closed point-of-dispensing model and Hospital Incident Command System to conduct mass vaccination events, and can adopt the "Flulapalooza method" as a best practice model to enhance efficiency.

An Overview of Vaccination Strategies and Antigen Delivery Systems for Streptococcus agalactiae Vaccines in Nile Tilapia (Oreochromis niloticus).

PubMed

Munang'andu, Hetron Mweemba; Paul, Joydeb; Evensen, Øystein

2016-12-13

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.

An Overview of Vaccination Strategies and Antigen Delivery Systems for Streptococcus agalactiae Vaccines in Nile Tilapia (Oreochromis niloticus)

PubMed Central

Munang’andu, Hetron Mweemba; Paul, Joydeb; Evensen, Øystein

2016-01-01

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

Production of recombinant subunit vaccines: protein immunogens, live delivery systems and nucleic acid vaccines.

PubMed

Liljeqvist, S; Ståhl, S

1999-07-30

The first scientific attempts to control an infectious disease can be attributed to Edward Jenner, who, in 1796 inoculated an 8-year-old boy with cowpox (vaccinia), giving the boy protection against subsequent challenge with virulent smallpox. Thanks to the successful development of vaccines, many major diseases, such as diphtheria, poliomyelitis and measles, are nowadays kept under control, and in the case of smallpox, the dream of eradication has been fulfilled. Yet, there is a growing need for improvements of existing vaccines in terms of increased efficacy and improved safety, besides the development of completely new vaccines. Better technological possibilities, combined with increased knowledge in related fields, such as immunology and molecular biology, allow for new vaccination strategies. Besides the classical whole-cell vaccines, consisting of killed or attenuated pathogens, new vaccines based on the subunit principle, have been developed, e.g. the Hepatitis B surface protein vaccine and the Haemophilus influenzae type b vaccine. Recombinant techniques are now dominating in the strive for an ideal vaccine, being safe and cheap, heat-stable and easy to administer, preferably single-dose, and capable of inducing broad immune response with life-long memory both in adults and in infants. This review will describe different recombinant approaches used in the development of novel subunit vaccines, including design and production of protein immunogens, the development of live delivery systems and the state-of-the-art for nucleic acids vaccines.

Strengthening routine immunization systems to improve global vaccination coverage.

PubMed

Sodha, S V; Dietz, V

2015-03-01

Global coverage with the third dose of diphtheria-tetanus-pertussis vaccine among children under 1 year of age stagnated at ∼ 83-84% during 2008-13. Annual World Health Organization and UNICEF-derived national vaccination coverage estimates. Incomplete vaccination is associated with poor socioeconomic status, lower education, non-use of maternal-child health services, living in conflict-affected areas, missed immunization opportunities and cancelled vaccination sessions. Vaccination platforms must expand to include older ages including the second year of life. Immunization programmes, including eradication and elimination initiatives such as those for polio and measles, must integrate within the broader health system. The Global Vaccine Action Plan (GVAP) 2011-20 is a framework for strengthening immunization systems, emphasizing country ownership, shared responsibility, equity, integration, sustainability and innovation. Immunization programmes should identify, monitor and evaluate gaps and interventions within the GVAP framework. Published by Oxford University Press 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

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

PubMed

Ozawa, Sachiko; Paina, Ligia; Qiu, Mary

2016-11-15

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

Effects of vaccines on the canine immune system.

PubMed Central

Phillips, T R; Jensen, J L; Rubino, M J; Yang, W C; Schultz, R D

1989-01-01

The effects of several commercially available polyvalent canine vaccines on the immune system of the dog were examined. The results demonstrated that the polyvalent vaccines used in this study significantly suppressed the absolute lymphocyte count and that most of the polyvalent vaccines significantly suppressed lymphocyte response to mitogen, but had no effect on natural effector cell activity, neutrophil chemiluminescence, nor antibody response to canine distemper virus. The individual vaccine components from the polyvalent vaccines when inoculated alone did not significantly suppress the lymphocyte response to mitogen. However, when canine distemper virus was combined with canine adenovirus type 1 or canine adenovirus type 2, significant suppression in lymphocyte responsiveness to mitogen occurred. The results indicate that interactions between canine distemper virus and canine adenovirus type 1 or canine adenovirus type 2 are responsible for the polyvalent vaccine induced suppression of lymphocyte responsiveness. PMID:2540897

Dynamics of vaccination strategies via projected dynamical systems.

PubMed

Cojocaru, Monica-Gabriela; Bauch, Chris T; Johnston, Matthew D

2007-07-01

Previous game theoretical analyses of vaccinating behaviour have underscored the strategic interaction between individuals attempting to maximise their health states, in situations where an individual's health state depends upon the vaccination decisions of others due to the presence of herd immunity. Here, we extend such analyses by applying the theories of variational inequalities (VI) and projected dynamical systems (PDS) to vaccination games. A PDS provides a dynamics that gives the conditions for existence, uniqueness and stability properties of Nash equilibria. In this paper, it is used to analyse the dynamics of vaccinating behaviour in a population consisting of distinct social groups, where each group has different perceptions of vaccine and disease risks. In particular, we study populations with two groups, where the size of one group is strictly larger than the size of the other group (a majority/minority population). We find that a population with a vaccine-inclined majority group and a vaccine-averse minority group exhibits higher average vaccine coverage than the corresponding homogeneous population, when the vaccine is perceived as being risky relative to the disease. Our model also reproduces a feature of real populations: In certain parameter regimes, it is possible to have a majority group adopting high vaccination rates and simultaneously a vaccine-averse minority group adopting low vaccination rates. Moreover, we find that minority groups will tend to exhibit more extreme changes in vaccinating behaviour for a given change in risk perception, in comparison to majority groups. These results emphasise the important role played by social heterogeneity in vaccination behaviour, while also highlighting the valuable role that can be played by PDS and VI in mathematical epidemiology.

Effects of a nurse-managed program on hepatitis A and B vaccine completion among homeless adults.

PubMed

Nyamathi, Adeline; Liu, Yihang; Marfisee, Mary; Shoptaw, Steven; Gregerson, Paul; Saab, Sammy; Leake, Barbara; Tyler, Darlene; Gelberg, Lillian

2009-01-01

Hepatitis B virus (HBV) infection constitutes a major health problem for homeless persons. Ability to complete an HBV vaccination series is complicated by the need to prioritize competing needs, such as addiction issues, safe places to sleep, and food, over health concerns. The objectives of this study were to evaluate the effectiveness of a nurse-case-managed intervention compared with that of two standard programs on completion of the combined hepatitis A virus (HAV) and HBV vaccine series among homeless adults and to assess sociodemographic factors and risk behaviors related to the vaccine completion. A randomized, three-group, prospective, quasi-experimental design was conducted with 865 homeless adults residing in homeless shelters, drug rehabilitation sites, and outdoor areas in the Skid Row area of Los Angeles. The programs included (a) nurse-case-managed sessions plus targeted hepatitis education, incentives, and tracking (NCMIT); (b) standard targeted hepatitis education plus incentives and tracking (SIT); and (c) standard targeted hepatitis education and incentives only (SI). Sixty-eight percent of the NCMIT participants completed the three-series vaccine at 6 months, compared with 61% of SIT participants and 54% of SI participants. NCMIT participants had almost 2 times greater odds of completing vaccination than those of participants in the SI program. Completers were more likely to be older, to be female, to report fair or poor health, and not to have participated in a self-help drug treatment program. Newly homeless White adults were significantly less likely than were African Americans to complete the vaccine series. The use of vaccination programs incorporating nurse case management and tracking is critical in supporting adherence to completion of a 6-month HAV/HBV vaccine. The finding that White homeless persons were the least likely to complete the vaccine series suggests that programs tailored to address their unique cultural issues are needed.

Understanding Clinic Practices for Human Papilloma Virus Vaccination Series Completion in Clinics That Provide Primary Care: Survey of Clinic Managers in Iowa.

PubMed

Askelson, Natoshia M; Edmonds, Stephanie W; Momany, Elizabeth T; Tegegne, Mesay A

2016-07-01

Rates for human papilloma virus (HPV) vaccination are low across the United States. Evidence-based-practices to increase immunization coverage have been recommended by public health organizations, yet many primary care clinics do not follow these practices. The purpose of this study was to examine if primary care clinics use these best practices to promote completion of the HPV vaccine series for their adolescent patients. Understanding the prevalence of evidence-based immunization strategies is key to increasing vaccination coverage. We mailed 914 surveys to clinic managers of clinics that provide primary care in Iowa. The survey content was based on immunization strategies related to clinic practice and policies that have been proven effective to promote the completion of the HPV vaccination series. Survey responses from 127 clinics were used in the final analysis. Most clinics always used the state's immunization information system to record HPV vaccinations (89.4%). Over a quarter of clinics (27.6%) did not use any type of reminder or recall system to alert parents or providers that an HPV vaccine was due, and 35.0% did not give the vaccine at sick visits. Clinics need to focus more on the recommended logistics and processes to ensure that patients receive the entire HPV vaccination series. Survey results indicate that clinics are not consistently implementing the recommended best practices to ensure that vaccination series are completed.

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

PubMed

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

2018-01-25

Currently four recombinant hepatitis B (HepB) vaccines are in use in the United States. HepB vaccines are recommended for infants, children and adults. We assessed adverse events (AEs) following HepB vaccines reported to the Vaccine Adverse Event Reporting System (VAERS), a national spontaneous reporting system. We searched VAERS for reports of AEs following single antigen HepB vaccine and HepB-containing vaccines (either given alone or with other vaccines), from January 2005 - December 2015. We conducted descriptive analyses and performed empirical Bayesian data mining to assess disproportionate reporting. We reviewed serious reports including reports of special interest. VAERS received 20,231 reports following HepB or HepB-containing vaccines: 10,291 (51%) in persons <2 years of age; 2588 (13%) in persons 2-18 years and 5867 (29%) in persons >18 years; for 1485 (7.3%) age was missing. Dizziness and nausea (8.4% each) were the most frequently reported AEs following a single antigen HepB vaccine: fever (23%) and injection site erythema (11%) were most frequent following Hep-containing vaccines. Of the 4444 (22%) reports after single antigen HepB vaccine, 303 (6.8%) were serious, including 45 deaths. Most commonly reported cause of death was Sudden Infant Death Syndrome (197). Most common non-death serious reports following single antigen HepB vaccines among infants aged <1 month, were nervous system disorders (15) among children aged 1-23 months; infections and infestation (8) among persons age 2-18 years blood and lymphatic systemic disorders; and general disorders and administration site conditions among persons age >18 years. Most common vaccination error following single antigen HepB was incorrect product storage. Review current U.S.-licensed HepB vaccines administered alone or in combination with other vaccines did not reveal new or unexpected safety concerns. Vaccination errors were identified which indicate the need for training and education

NSW Annual vaccine-preventable disease report, 2011.

PubMed

Rosewell, Alexander; Spokes, Paula J; Gilmour, Robin E

2012-12-01

To describe the epidemiology of selected vaccine-preventable diseases in NSW for 2011. Data from the NSW Notifiable Conditions Information Management System were analysed by: local health district of residence, age, Aboriginality, vaccination status, and organism, where available. Risk factor and vaccination status data were collected by public health units for case-patients following notification under the NSW Public Health Act 1991*. Outbreaks of measles and pertussis were reported in 2011, associated with unimmunised groups for measles, and a variety of factors for pertussis. Notification rates for other selected vaccine-preventable diseases remained stable. Vaccine-preventable diseases are generally well controlled in NSW. However, pertussis remains an important public health issue. To prevent measles high population vaccination coverage, including vaccination in risk groups, is essential.

Integration of data from a safety net health care system into the Vaccine Safety Datalink.

PubMed

Hambidge, Simon J; Ross, Colleen; Shoup, Jo Ann; Wain, Kris; Narwaney, Komal; Breslin, Kristin; Weintraub, Eric S; McNeil, Michael M

2017-03-01

In 2013 the Institute of Medicine suggested that the Vaccine Safety DataLink (VSD) should broaden its population by including data of more patients from low income and racially and ethnically diverse backgrounds. In response, Kaiser Permanente Colorado (KPCO) partnered with Denver Health (DH), an integrated safety net health care system, to explore the integration of DH data. We compared three different methods (reference date of September 1, 2013): "Empanelment" (any patient who has had a primary care visit in the past 18months), "Proxy-enrollment" (two health care visits in 3years separated by 90days), and "Enrollment" in a managed care plan. For each of these methods, we compared cohort size, vaccination rates, socio-demographic characteristics, and health care utilization. The empaneled population at DH provided the best comparison to KPCO. DH's empaneled population was 111,330 (57,173 adults; 54,157 children), while KPCO had 436,290 empaneled patients (336,462 adults; 99,828 children). Vaccination rates in both health care systems for empaneled patients were comparable. Two year-old up-to-date coverage rates were 83.2% (KPCO) and 86.9% (DH); rates for adolescent Tdap and MCV4 were 85.5% (KPCO) and 90.6% (DH). There were significant differences in the two populations in age, gender, race, preferred language, and % Federal Poverty Level (FPL) (DH 70.7%<100% FPL; KPCO 17.4%), as well as in healthcare utilization - for example pediatric emergency department utilization was twice as high at DH. Using a cohort of "empaneled" patients, it is possible to integrate data from a safety net health care system that does not have a uniform managed care population into the VSD, and to compare vaccination rates, socio-demographic characteristics, and health care utilization across the two systems. The KPCO-DH collaboration may serve as a model for incorporating data from a safety net healthcare system into the VSD. Copyright © 2017 Elsevier Ltd. All rights reserved.

Systemic and Local Vaccination against Breast Cancer with Minimum Autoimmune Sequelae

DTIC Science & Technology

2012-10-01

AD_________________ Award Number: W81XWH-10-1-0466 TITLE: Systemic and Local Vaccination against...September 2012 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Systemic and Local Vaccination against Breast Cancer with Minimum Autoimmune Sequelae 5b...eliminate the tumor by vaccination and local ablation to render long-term immune protection without excessive autoimmune sequelae. Complimenting this

Systemic And Local Vaccination Against Breast Cancer With Minimum Autoimmune Sequelae

DTIC Science & Technology

2011-10-01

AD_________________ Award Number: W81XWH-10-1-0466 TITLE: Systemic and Local Vaccination against...2011 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Systemic and Local Vaccination against Breast Cancer with Minimum Autoimmune Sequelae 5b. GRANT...eliminate the tumor by vaccination and local ablation to render long-term immune protection without excessive autoimmune sequelae. Complimenting this

Standardized emergency management system and response to a smallpox emergency.

PubMed

Kim-Farley, Robert J; Celentano, John T; Gunter, Carol; Jones, Jessica W; Stone, Rogelio A; Aller, Raymond D; Mascola, Laurene; Grigsby, Sharon F; Fielding, Jonathan E

2003-01-01

The smallpox virus is a high-priority, Category-A agent that poses a global, terrorism security risk because it: (1) easily can be disseminated and transmitted from person to person; (2) results in high mortality rates and has the potential for a major public health impact; (3) might cause public panic and social disruption; and (4) requires special action for public health preparedness. In recognition of this risk, the Los Angeles County Department of Health Services (LAC-DHS) developed the Smallpox Preparedness, Response, and Recovery Plan for LAC to prepare for the possibility of an outbreak of smallpox. A unique feature of the LAC-DHS plan is its explicit use of the Standardized Emergency Management System (SEMS) framework for detailing the functions needed to respond to a smallpox emergency. The SEMS includes the Incident Command System (ICS) structure (management, operations, planning/intelligence, logistics, and finance/administration), the mutual-aid system, and the multi/interagency coordination required during a smallpox emergency. Management for incident command includes setting objectives and priorities, information (risk communications), safety, and liaison. Operations includes control and containment of a smallpox outbreak including ring vaccination, mass vaccination, adverse events monitoring and assessment, management of confirmed and suspected smallpox cases, contact tracing, active surveillance teams and enhanced hospital-based surveillance, and decontamination. Planning/intelligence functions include developing the incident action plan, epidemiological investigation and analysis of smallpox cases, and epidemiological assessment of the vaccination coverage status of populations at risk. Logistics functions include receiving, handling, inventorying, and distributing smallpox vaccine and vaccination clinic supplies; personnel; transportation; communications; and health care of personnel. Finally, finance/administration functions include monitoring

Sylvatic plague vaccine and management of prairie dogs

USGS Publications Warehouse

Rocke, Tonie E.

2012-01-01

Scientists at the USGS National Wildlife Health Center (NWHC), in collaboration with colleagues at the University of Wisconsin (UW), have developed a sylvatic plague vaccine that shows great promise in protecting prairie dogs against plague (Mencher and others, 2004; Rocke and others, 2010). Four species of prairie dogs reside in the United States and Canada, and all are highly susceptible to plague and regularly experience outbreaks with devastating losses. Along with habitat loss and poisoning, plague has contributed to a significant historical decline in prairie dog populations. By some estimates, prairie dogs now occupy only 1 to 2 percent of their former range (Proctor and others, 2006), with prairie dog colonies being now much smaller and fragmented than they were historically, making individual colonies more vulnerable to elimination by plague (Antolin and others, 2002). At least one species, the Utah prairie dog (Cynomys parvidens) is listed by the U.S. Fish and Wildlife Service (FWS) as "threatened." Controlling plague is a vital concern for ongoing management and conservation efforts for prairie dogs. Current efforts to halt the spread of plague in prairie dog colonies typically rely on dusting individual prairie dog burrows with pesticides to kill plague-infected fleas. Although flea-control insecticides, such as deltamethrin, are useful in stopping plague outbreaks in these prairie dog colonies, dusting of burrows is labor intensive and time consuming and may affect other insects and arthropods. As an alternative approach, NWHC and UW scientists developed a sylvatic plague vaccine (SPV) for prairie dogs that can be delivered via oral bait. Laboratory studies have shown that consumption of this vaccine-laden bait by different prairie dog species results in significant protection against plague infection that can last for at least 9 months (Rocke and others, 2010; Rocke, unpublished). Work has now shifted to optimizing baits and distribution methods for

Vaccine wastage in Nigeria: An assessment of wastage rates and related vaccinator knowledge, attitudes and practices.

PubMed

Wallace, Aaron S; Willis, Fred; Nwaze, Eric; Dieng, Boubacar; Sipilanyambe, Naawa; Daniels, Danni; Abanida, Emmanuel; Gasasira, Alex; Mahmud, Mustapha; Ryman, Tove K

2017-12-04

implementation of vaccine management guidelines, missed opportunities to vaccinate, and lyophilized vaccine wastage rates below expected rates. Missed opportunities for vaccination may occur due to how the health system's contradicting policies may force health workers to prioritize reduced wastage rates over vaccine administration, particularly for multi-dose vials. Published by Elsevier Ltd.

Systemic humoral immunity in beef bulls following therapeutic vaccination against Tritrichomonas foetus.

PubMed

Alling, Christopher; Rae, D Owen; Ma, Xiaojie; Neumann, Laura; Lollis, L Gene; Steele, Elizabeth; Yelvington, John; Naikare, Hemant K; Walden, Heather Stockdale; Crews, John; Boughton, Raoul

2018-05-15

The utility of therapeutic vaccination of bulls against Tritrichomonas foetus has been advocated in previous studies, but anecdotal reports suggest this practice does not clear infections and may additionally confound diagnostic testing by reducing parasite burdens below detectable limits. The objective of this study was to characterize the systemic humoral immune response to therapeutic vaccination in T. foetus-infected bulls over a period of four months using an indirect ELISA and to compare the dynamics of this response to culture and PCR results to establish the existence of a relationship (or lack thereof) between immunization and infection status. A study population of 4- to 6-year-old T. foetus-infected beef bulls (n = 20) was divided equally into a treatment group and a control group. The treatment group received two doses of commercially prepared whole cell killed vaccine 2 weeks apart while the control group received injections of vaccine diluent. Blood samples were collected at each injection and at 4 subsequent dates every 4 weeks thereafter (i.e. 0, 2, 6, 10, 14, and 18 wks) to measure IgG 1 and IgG 2 antibody subisotype response via an indirect ELISA. Preputial smegma samples were collected at the four monthly intervals following vaccination for diagnosis of infection via InPouch™ culture, Modified Diamond's Medium (MDM) culture, and PCR. Humoral response for both IgG isotypes from week 2 through week 18 were significantly increased in vaccinates compared to controls. No significant decrease in infection prevalence was detected in the treatment group for any of the diagnostic methods used. The apparent lack of pathogen clearance during a stimulated immune response suggests that therapeutic vaccination may not be a useful T. foetus management practice. Copyright © 2018 Elsevier B.V. All rights reserved.

Vaccine-preventable infections in Systemic Lupus Erythematosus

PubMed Central

Murdaca, Giuseppe; Orsi, Andrea; Spanò, Francesca; Faccio, Valeria; Puppo, Francesco; Durando, Paolo; Icardi, Giancarlo; Ansaldi, Filippo

2016-01-01

Systemic Lupus Erythematosus (SLE) is characterized by abnormal autoantibody production and clearance. Infections are among the most important causes of morbidity and mortality in SLE patients; they have an increased frequency of severe bacterial and viral infections possibly due to inherited genetic and immunologic defects and to immunosuppressive therapies. In addition, infectious agents can switch on lupus disease expression and activity. Among the strategies to reduce the risk of infection, vaccination can be considered the most reliable option. Most vaccines are effective and safe in SLE patients, although in certain cases immunogenicity may be sub-optimal and vaccination can trigger a flare. Although these issues are currently unresolved, the risk benefit balance is in favor for vaccination to reduce the risk of infection in SLE patients. In the present review we discuss the preventive strategies currently recommended to reduce bacterial and viral infections in SLE. PMID:26750996

Measuring vaccine confidence: analysis of data obtained by a media surveillance system used to analyse public concerns about vaccines.

PubMed

Larson, Heidi J; Smith, David M D; Paterson, Pauline; Cumming, Melissa; Eckersberger, Elisabeth; Freifeld, Clark C; Ghinai, Isaac; Jarrett, Caitlin; Paushter, Louisa; Brownstein, John S; Madoff, Lawrence C

2013-07-01

The intensity, spread, and effects of public opinion about vaccines are growing as new modes of communication speed up information sharing, contributing to vaccine hesitancy, refusals, and disease outbreaks. We aimed to develop a new application of existing surveillance systems to detect and characterise early signs of vaccine issues. We also aimed to develop a typology of concerns and a way to assess the priority of each concern. Following preliminary research by The Vaccine Confidence Project, media reports (eg, online articles, blogs, government reports) were obtained using the HealthMap automated data collection system, adapted to monitor online reports about vaccines, vaccination programmes, and vaccine-preventable diseases. Any reports that did not meet the inclusion criteria--any reference to a human vaccine or vaccination campaign or programme that was accessible online--were removed from analysis. Reports were manually analysed for content and categorised by concerns, vaccine, disease, location, and source of report, and overall positive or negative sentiment towards vaccines. They were then given a priority level depending on the seriousness of the reported event and time of event occurrence. We used descriptive statistics to analyse the data collected during a period of 1 year, after refinements to the search terms and processes had been made. We analysed data from 10,380 reports (from 144 countries) obtained between May 1, 2011, and April 30, 2012. 7171 (69%) contained positive or neutral content and 3209 (31%) contained negative content. Of the negative reports, 1977 (24%) were associated with impacts on vaccine programmes and disease outbreaks; 1726 (21%) with beliefs, awareness, and perceptions; 1371 (16%) with vaccine safety; and 1336 (16%) with vaccine delivery programmes. We were able to disaggregate the data by country and vaccine type, and monitor evolution of events over time and location in specific regions where vaccine concerns were high

Vaccines: From Empirical Development to Rational Design

PubMed Central

Rueckert, Christine; Guzmán, Carlos A.

2012-01-01

Infectious diseases are responsible for an overwhelming number of deaths worldwide and their clinical management is often hampered by the emergence of multi-drug-resistant strains. Therefore, prevention through vaccination currently represents the best course of action to combat them. However, immune escape and evasion by pathogens often render vaccine development difficult. Furthermore, most currently available vaccines were empirically designed. In this review, we discuss why rational design of vaccines is not only desirable but also necessary. We introduce recent developments towards specifically tailored antigens, adjuvants, and delivery systems, and discuss the methodological gaps and lack of knowledge still hampering true rational vaccine design. Finally, we address the potential and limitations of different strategies and technologies for advancing vaccine development. PMID:23144616

Childhood vaccines and Kawasaki disease, Vaccine Safety Datalink, 1996-2006.

PubMed

Abrams, Joseph Y; Weintraub, Eric S; Baggs, James M; McCarthy, Natalie L; Schonberger, Lawrence B; Lee, Grace M; Klein, Nicola P; Belongia, Edward A; Jackson, Michael L; Naleway, Allison L; Nordin, James D; Hambidge, Simon J; Belay, Ermias D

2015-01-03

Kawasaki disease is a childhood vascular disorder of unknown etiology. Concerns have been raised about vaccinations being a potential risk factor for Kawasaki disease. Data from the Vaccine Safety Datalink were collected on children aged 0-6 years at seven managed care organizations across the United States. Defining exposure as one of several time periods up to 42 days after vaccination, we conducted Poisson regressions controlling for age, sex, season, and managed care organization to determine if rates of physician-diagnosed and verified Kawasaki disease were elevated following vaccination compared to rates during all unexposed periods. We also performed case-crossover analyses to control for unmeasured confounding. A total of 1,721,186 children aged 0-6 years from seven managed care organizations were followed for a combined 4,417,766 person-years. The rate of verified Kawasaki disease was significantly lower during the 1-42 days after vaccination (rate ratio=0.50, 95% CL=0.27-0.92) and 8-42 days after vaccination (rate ratio=0.45, 95% CL=0.22-0.90) compared to rates during unexposed periods. Breaking down the analysis by vaccination category did not identify a subset of vaccines which was solely responsible for this association. The case-crossover analyses revealed that children with Kawasaki disease had lower rates of vaccination in the 42 days prior to symptom onset for both physician-diagnosed Kawasaki disease (rate ratio=0.79, 95% CL=0.64-0.97) and verified Kawasaki disease (rate ratio=0.38, 95% CL=0.20-0.75). Childhood vaccinations' studied did not increase the risk of Kawasaki disease; conversely, vaccination was associated with a transient decrease in Kawasaki disease incidence. Verifying and understanding this potential protective effect could yield clues to the underlying etiology of Kawasaki disease. Copyright © 2014. Published by Elsevier Ltd.

Mitochondrion: A Promising Target for Nanoparticle-Based Vaccine Delivery Systems

PubMed Central

Wen, Ru; Umeano, Afoma C.; Francis, Lily; Sharma, Nivita; Tundup, Smanla; Dhar, Shanta

2016-01-01

Vaccination is one of the most popular technologies in disease prevention and eradication. It is promising to improve immunization efficiency by using vectors and/or adjuvant delivery systems. Nanoparticle (NP)-based delivery systems have attracted increasing interest due to enhancement of antigen uptake via prevention of vaccine degradation in the biological environment and the intrinsic immune-stimulatory properties of the materials. Mitochondria play paramount roles in cell life and death and are promising targets for vaccine delivery systems to effectively induce immune responses. In this review, we focus on NPs-based delivery systems with surfaces that can be manipulated by using mitochondria targeting moieties for intervention in health and disease. PMID:27258316

Human Papillomavirus Vaccine as an Anti-cancer Vaccine: Collaborative Efforts to Promote HPV Vaccine in the National Comprehensive Cancer Control Program

PubMed Central

Townsend, Julie S.; Steele, C. Brooke; Hayes, Nikki; Bhatt, Achal; Moore, Angela R.

2018-01-01

Background Widespread use of the HPV vaccine has the potential to reduce incidence from HPV-associated cancers. However, vaccine uptake among adolescents remains well below the Healthy People 2020 targets. The Centers for Disease Control and Prevention (CDC)’s National Comprehensive Cancer Control Program awardees (NCCCP) are well positioned to work with immunization programs to increase vaccine uptake. Methods CDC’s chronic disease management information system was queried for objectives and activities associated with HPV vaccine that were reported by NCCCP awardees from 2013 – 2016 as part of program reporting requirements. A content analysis was conducted on the query results to categorize interventions according to strategies outlined in The Guide to Community Preventive Services and the 2014 President’s Cancer Panel report. Results Sixty-two percent of NCCCP awardees had planned or implemented at least one activity since 2013 to address low HPV vaccination coverage in their jurisdictions. Most NCCCP awardees (86%) reported community education activities, while 65% reported activities associated with provider education. Systems-based strategies such as client reminders or provider assessment and feedback were each reported by less than 25% of NCCCP awardees. Conclusion Many NCCCP awardees report planning or implementing activities to address low HPV vaccination coverage, often in conjunction with state immunization programs. NCCCP awardees can play a role in increasing HPV vaccination coverage through their cancer prevention and control expertise and access to partners in the health care community. PMID:28263672

[VACCINES].

PubMed

Bellver Capella, Vincente

2015-10-01

Vaccines are an extraordinary instrument of immunization of the population against infectious diseases. Around them there are many ethical issues. One of the most debated is what to do with certain groups opposition to vaccination of their children. States have managed in different ways the conflict between the duty of vaccination and the refusal to use vaccines: some impose the vaccination and others simply promote it. In this article we deal with which of these two approaches is the most suitable from an ethical and legal point of view. We stand up for the second option, which is the current one in Spain, and we propose some measures which should be kept in mind to improve immunization programs.

Use of geographic information systems in rabies vaccination campaigns.

PubMed

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

2008-12-01

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

Demonstration of systemic infection of BVDV Vaccine virus after vaccination in presence of PI calves

USDA-ARS?s Scientific Manuscript database

Bovine viral diarrhea virus (BVDV) was detected during routine necropsy of calves, from a well vaccinated, large Jersey/Holstein dairy herd (n=10,000) in California, that succumbed to ill thrift. According to herd management, BVDV has not been considered a problem in the past. The herd had been exte...

Methodology for Knowledge Synthesis of the Management of Vaccination Pain and Needle Fear.

PubMed

Taddio, Anna; McMurtry, C Meghan; Shah, Vibhuti; Yoon, Eugene W; Uleryk, Elizabeth; Pillai Riddell, Rebecca; Lang, Eddy; Chambers, Christine T; Noel, Melanie; MacDonald, Noni E

2015-10-01

A knowledge synthesis was undertaken to inform the development of a revised and expanded clinical practice guideline about managing vaccination pain in children to include the management of pain across the lifespan and the management of fear in individuals with high levels of needle fear. This manuscript describes the methodological details of the knowledge synthesis and presents the list of included clinical questions, critical and important outcomes, search strategy, and search strategy results. The Grading of Assessments, Recommendations, Development and Evaluation (GRADE) and Cochrane methodologies provided the general framework. The project team voted on clinical questions for inclusion and critically important and important outcomes. A broad search strategy was used to identify relevant randomized-controlled trials and quasi-randomized-controlled trials. Quality of research evidence was assessed using the Cochrane risk of bias tool and quality across studies was assessed using GRADE. Multiple measures of the same construct within studies (eg, observer-rated and parent-rated infant distress) were combined before pooling. The standardized mean difference and 95% confidence intervals (CI) or relative risk and 95% CI was used to express the effects of an intervention. Altogether, 55 clinical questions were selected for inclusion in the knowledge synthesis; 49 pertained to pain management during vaccine injections and 6 pertained to fear management in individuals with high levels of needle fear. Pain, fear, and distress were typically prioritized as critically important outcomes across clinical questions. The search strategy identified 136 relevant studies. This manuscript describes the methodological details of a knowledge synthesis about pain management during vaccination and fear management in individuals with high levels of needle fear. Subsequent manuscripts in this series will present the results for the included questions.

Biotechnology and the transformation of vaccine innovation: The case of the hepatitis B vaccines 1968-2000.

PubMed

Huzair, Farah; Sturdy, Steve

2017-08-01

The approval, from 1986, of a series of recombinant hepatitis B vaccines was a landmark both in the growth of biotechnology and in the development of the vaccine innovation system. In this paper, we show how the early development of the hepatitis B vaccines was shaped by a political and economic context that newly favoured commercialisation of academic research, including the appropriation and management of intellectual property; we elucidate the contingent interests and motivations that led new biotechnology companies and established pharmaceutical businesses to invest in developing recombinant vaccines specifically against hepatitis B; and we show how these and other factors combined to make those vaccines an unexpected commercial success. Broadening the scope of our analysis to include not just North America and Europe but also low- and middle-income countries, we show how the development of the hepatitis B vaccines facilitated the emergence of a two-tier innovation system structured by tensions between the demands for commercial profitability on the one hand, and the expectation of public health benefit for low- and middle-income countries on the other. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Casting off vaccine supply charity -- the pace quickens. CVI goal: quality vaccines for all children.

PubMed

1995-10-01

Several proposals are offered for production of high-quality vaccines within developing countries. The World Health Organization's Vaccine Supply and Quality (VSQ) team from the Global Program for Vaccines and Immunization (GPV) visited 10 countries (Bangladesh, Brazil, Egypt, India, Indonesia, Iran, Mexico, Pakistan, Philippines, and South Africa) out of 14 priority countries (China, Russia, Thailand, and Vietnam were not visited) producing vaccines and found only two with a quality control system that was acceptable. Vaccine-producing countries are urged to consider the full costs of production that include necessary infrastructure, an independent national control authority and laboratory, manufacturers with managerial autonomy, and manufacturers with good management, a qualified staff, and adequate technology. UNICEF has urged both private and public sectors to combine forces in bringing down the price of new vaccines for distribution to a very large market. Some imaginative proposals were made by some manufacturers for vaccine production and supply for a range of less traditional vaccines. The Director of the Massachusetts Public Health Biologic Laboratories proposed the formation of a consortium of vaccine manufacturers who would support public health priorities for market-affordable, simple vaccines against the major childhood diseases. The aim would be international validation of high-quality local vaccine production in developing countries, ease of research collaboration, improvement in information exchange between countries, and structured assistance. Lack of political commitment has been blamed for poor quality local production. A small cooperative effort among some Latin American countries, the Pan American Association's Regional Vaccine System for Latin America (SIREVA), is backed by the Children's Vaccine Initiative. SIREVA is a consortium of manufacturers in Brazil, Chile, and Mexico that plans joint development of some vaccines. Donor assistance is

Progress in Childhood Vaccination Data in Immunization Information Systems - United States, 2013-2016.

PubMed

Murthy, Neil; Rodgers, Loren; Pabst, Laura; Fiebelkorn, Amy Parker; Ng, Terence

2017-11-03

In 2016, 55 jurisdictions in 49 states and six cities in the United States* used immunization information systems (IISs) to collect and manage immunization data and support vaccination providers and immunization programs. To monitor progress toward achieving IIS program goals, CDC surveys jurisdictions through an annual self-administered IIS Annual Report (IISAR). Data from the 2013-2016 IISARs were analyzed to assess progress made in four priority areas: 1) data completeness, 2) bidirectional exchange of data with electronic health record systems, 3) clinical decision support for immunizations, and 4) ability to generate childhood vaccination coverage estimates. IIS participation among children aged 4 months through 5 years increased from 90% in 2013 to 94% in 2016, and 33 jurisdictions reported ≥95% of children aged 4 months through 5 years participating in their IIS in 2016. Bidirectional messaging capacity in IISs increased from 25 jurisdictions in 2013 to 37 in 2016. In 2016, nearly all jurisdictions (52 of 55) could provide automated provider-level coverage reports, and 32 jurisdictions reported that their IISs could send vaccine forecasts to providers via Health Level 7 (HL7) messaging, up from 17 in 2013. Incremental progress was made in each area since 2013, but continued effort is needed to implement these critical functionalities among all IISs. Success in these priority areas, as defined by the IIS Functional Standards (1), bolsters clinicians' and public health practitioners' ability to attain high vaccination coverage in pediatric populations, and prepares IISs to develop more advanced functionalities to support state/local immunization services. Success in these priority areas also supports the achievement of federal immunization objectives, including the use of IISs as supplemental sampling frames for vaccination coverage surveys like the National Immunization Survey (NIS)-Child, reducing data collection costs, and supporting increased precision

Countermeasures and vaccination against terrorism using smallpox: pre-event and post-event smallpox vaccination and its contraindications.

PubMed

Sato, Hajime

2011-09-01

Smallpox, when used as a biological weapon, presents a serious threat to civilian populations. Core components of the public health management of a terrorism attack using smallpox are: vaccination (ring vaccination and mass vaccination), adverse event monitoring, confirmed and suspected smallpox case management, contact management, identifying, tracing, monitoring contacts, and quarantine. Above all, pre-event and post-event vaccination is an indispensable part of the strategies. Since smallpox patients are most infectious from onset of the rash through the first 7-10 days of the rash, vaccination should be administered promptly within a limited time frame. However, vaccination can accompany complications, such as postvaccinial encephalitis, progressive vaccinia, eczema vaccinatum, and generalized vaccinia. Therefore, vaccination is not recommended for certain groups. Public health professionals, as well as physicians and government officials, should also be well equipped with all information necessary for appropriate and effective smallpox management in the face of such a bioterrorism attack.

Assessing the Importance of Domestic Vaccine Manufacturing Centers: An Overview of Immunization Programs, Vaccine Manufacture, and Distribution.

PubMed

Rey-Jurado, Emma; Tapia, Felipe; Muñoz-Durango, Natalia; Lay, Margarita K; Carreño, Leandro J; Riedel, Claudia A; Bueno, Susan M; Genzel, Yvonne; Kalergis, Alexis M

2018-01-01

Vaccines have significantly reduced the detrimental effects of numerous human infectious diseases worldwide, helped to reduce drastically child mortality rates and even achieved eradication of major pathogens, such as smallpox. These achievements have been possible due to a dedicated effort for vaccine research and development, as well as an effective transfer of these vaccines to public health care systems globally. Either public or private institutions have committed to developing and manufacturing vaccines for local or international population supply. However, current vaccine manufacturers worldwide might not be able to guarantee sufficient vaccine supplies for all nations when epidemics or pandemics events could take place. Currently, different countries produce their own vaccine supplies under Good Manufacturing Practices, which include the USA, Canada, China, India, some nations in Europe and South America, such as Germany, the Netherlands, Italy, France, Argentina, and Brazil, respectively. Here, we discuss some of the vaccine programs and manufacturing capacities, comparing the current models of vaccine management between industrialized and developing countries. Because local vaccine production undoubtedly provides significant benefits for the respective population, the manufacture capacity of these prophylactic products should be included in every country as a matter of national safety.

Assessing the Importance of Domestic Vaccine Manufacturing Centers: An Overview of Immunization Programs, Vaccine Manufacture, and Distribution

PubMed Central

Rey-Jurado, Emma; Tapia, Felipe; Muñoz-Durango, Natalia; Lay, Margarita K.; Carreño, Leandro J.; Riedel, Claudia A.; Bueno, Susan M.; Genzel, Yvonne; Kalergis, Alexis M.

2018-01-01

Vaccines have significantly reduced the detrimental effects of numerous human infectious diseases worldwide, helped to reduce drastically child mortality rates and even achieved eradication of major pathogens, such as smallpox. These achievements have been possible due to a dedicated effort for vaccine research and development, as well as an effective transfer of these vaccines to public health care systems globally. Either public or private institutions have committed to developing and manufacturing vaccines for local or international population supply. However, current vaccine manufacturers worldwide might not be able to guarantee sufficient vaccine supplies for all nations when epidemics or pandemics events could take place. Currently, different countries produce their own vaccine supplies under Good Manufacturing Practices, which include the USA, Canada, China, India, some nations in Europe and South America, such as Germany, the Netherlands, Italy, France, Argentina, and Brazil, respectively. Here, we discuss some of the vaccine programs and manufacturing capacities, comparing the current models of vaccine management between industrialized and developing countries. Because local vaccine production undoubtedly provides significant benefits for the respective population, the manufacture capacity of these prophylactic products should be included in every country as a matter of national safety. PMID:29403503

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Adams, Leslie G.; Khare, Sangeeta; Lawhon, Sara D.

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

Particulate delivery systems for vaccination against bioterrorism agents and emerging infectious pathogens

PubMed Central

Fan, Yuchen; Moon, James J.

2016-01-01

Bioterrorism agents that can be easily transmitted with high mortality rates and cause debilitating diseases pose major threats to national security and public health. The recent Ebola virus outbreak in West Africa and ongoing Zika virus outbreak in Brazil, now spreading throughout Latin America, are case examples of emerging infectious pathogens that have incited widespread fear and economic and social disruption on a global scale. Prophylactic vaccines would provide effective countermeasures against infectious pathogens and biological warfare agents. However, traditional approaches relying on attenuated or inactivated vaccines have been hampered by their unacceptable levels of reactogenicity and safety issues, whereas subunit antigen-based vaccines suffer from suboptimal immunogenicity and efficacy. In contrast, particulate vaccine delivery systems offer key advantages, including efficient and stable delivery of subunit antigens, co-delivery of adjuvant molecules to bolster immune responses, low reactogenicity due to the use of biocompatible biomaterials, and robust efficiency to elicit humoral and cellular immunity in systemic and mucosal tissues. Thus, vaccine nanoparticles and microparticles are promising platforms for clinical development of biodefense vaccines. In this review, we summarize the current status of research efforts to develop particulate vaccine delivery systems against bioterrorism agents and emerging infectious pathogens. PMID:27038091

Evaluating Childhood Vaccination Coverage of NIP Vaccines: Coverage Survey versus Zhejiang Provincial Immunization Information System

PubMed Central

Hu, Yu; Chen, Yaping

2017-01-01

Vaccination coverage in Zhejiang province, east China, is evaluated through repeated coverage surveys. The Zhejiang provincial immunization information system (ZJIIS) was established in 2004 with links to all immunization clinics. ZJIIS has become an alternative to quickly assess the vaccination coverage. To assess the current completeness and accuracy on the vaccination coverage derived from ZJIIS, we compared the estimates from ZJIIS with the estimates from the most recent provincial coverage survey in 2014, which combined interview data with verified data from ZJIIS. Of the enrolled 2772 children in the 2014 provincial survey, the proportions of children with vaccination cards and registered in ZJIIS were 94.0% and 87.4%, respectively. Coverage estimates from ZJIIS were systematically higher than the corresponding estimates obtained through the survey, with a mean difference of 4.5%. Of the vaccination doses registered in ZJIIS, 16.7% differed from the date recorded in the corresponding vaccination cards. Under-registration in ZJIIS significantly influenced the coverage estimates derived from ZJIIS. Therefore, periodic coverage surveys currently provide more complete and reliable results than the estimates based on ZJIIS alone. However, further improvement of completeness and accuracy of ZJIIS will likely allow more reliable and timely estimates in future. PMID:28696387

Evaluating Childhood Vaccination Coverage of NIP Vaccines: Coverage Survey versus Zhejiang Provincial Immunization Information System.

PubMed

Hu, Yu; Chen, Yaping

2017-07-11

Vaccination coverage in Zhejiang province, east China, is evaluated through repeated coverage surveys. The Zhejiang provincial immunization information system (ZJIIS) was established in 2004 with links to all immunization clinics. ZJIIS has become an alternative to quickly assess the vaccination coverage. To assess the current completeness and accuracy on the vaccination coverage derived from ZJIIS, we compared the estimates from ZJIIS with the estimates from the most recent provincial coverage survey in 2014, which combined interview data with verified data from ZJIIS. Of the enrolled 2772 children in the 2014 provincial survey, the proportions of children with vaccination cards and registered in ZJIIS were 94.0% and 87.4%, respectively. Coverage estimates from ZJIIS were systematically higher than the corresponding estimates obtained through the survey, with a mean difference of 4.5%. Of the vaccination doses registered in ZJIIS, 16.7% differed from the date recorded in the corresponding vaccination cards. Under-registration in ZJIIS significantly influenced the coverage estimates derived from ZJIIS. Therefore, periodic coverage surveys currently provide more complete and reliable results than the estimates based on ZJIIS alone. However, further improvement of completeness and accuracy of ZJIIS will likely allow more reliable and timely estimates in future.

Biodegradable Vaccine Microcapsules for Systemic and Mucosal Immunization against RVF and VEE Viruses

DTIC Science & Technology

1992-03-31

C-0113 TITLE: BIODEGRADABLE VACCINE MICROCAPSULES FOR SYSTEMIC AND MUCOSAL IMMUNIZATION AGAINST RVF and VEE Viruses PRINCIPAL INVESTIGATOR: John H...approximately 0.8% by weight VEE vaccine. As measured by ELISA, immunization of mice with from 3 to 100 I.tg of microencapsulated vaccine potentiated the plasma...PAGESuzodegradable microspheres, VEE vaccine, RVF vaccine, vaccines RA I, BD, Lab Animals, Mice, Microencapsulation 16. PRICE COOJE 17, SECURITY

Impact of tetanus, diphtheria, and acellular pertussis (Tdap) vaccine use in wound management on health care costs and pertussis cases.

PubMed

Talbird, Sandra E; Graham, Jonathan; Mauskopf, Josephine; Masseria, Cristina; Krishnarajah, Girishanthy

2015-01-01

The Advisory Committee on Immunization Practices (ACIP) recommends the use of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine for routine wound management in adolescents and adults who require a tetanus toxoid-containing vaccine who were vaccinated ≥ 5 years earlier with tetanus toxoid, reduced diphtheria toxoid (Td) vaccine, and who have not previously received Tdap. To estimate the overall budget and health impact of vaccinating individuals presenting for wound management with Tdap instead of Td vaccine, the current standard of care in practices that do not use Tdap for purposes of wound management. A decision-analytic economic model was developed to estimate the expected increase in direct medical costs and the expected number of cases of pertussis avoided associated with the use of Tdap instead of Td vaccine in the wound management setting. Patients eligible for Tdap were aged 10+ years and required a tetanus-containing vaccine. Age-specific wound incidence data and Td and Tdap vaccination rates were taken from the National Health Interview Survey and the National Immunization Survey for the most recent available year. Age-specific pertussis incidence used in this analysis (151 per 100,000 for adolescents, 366 per 100,000 for those aged 20-64 years, and 176 per 100,000 for those aged 65+ years) used reported incidence rates adjusted by a factor of 10 for adolescents and by a factor of 100 for adults, based on assumptions previously made by ACIP to account for underreporting. Vaccine wholesale acquisition costs without federal excise tax were assumed in the base case. Efficacy of vaccination with Tdap in preventing pertussis was based on clinical trial data. Possible herd immunity effects of vaccination were not included in the model. Costs associated with vaccination and treatment of pertussis cases were reported as total annual costs and per-member-per-month (PMPM) costs for hypothetical health plans and for the U

Addressing parental concerns about pain during childhood vaccination: is there enough time to include pain management in the ambulatory setting?

PubMed

Taddio, Anna; Hogan, Mary-Ellen; Gerges, Sandra; Girgis, Angela; Moyer, Paul; Wang, Linda; Murphy, Claire; Ho, Tommy; Greenberg, Saul; Ipp, Moshe

2012-01-01

Pain from vaccine injections remains undertreated, despite the availability of numerous pain-relieving strategies. Healthcare providers report lack of time within current office workflows as a major barrier to routine pain management. The objective was to document the total time involved in outpatient vaccine appointments to test the hypothesis that offering pain-relieving strategies can be practically implemented when considering the element of time to vaccine injection. Prospective naturalistic study in 8 urban outpatient primary care clinics (4 pediatric and 4 family practice) in Toronto. For 48 to 59 consecutive childhood vaccination appointments at each site, child waiting time from clinic arrival until first vaccine injection was tracked. Altogether, 405 vaccine appointments were included. The median age of the child undergoing vaccination was 12 months. The mean (SD) time from clinic arrival until first vaccine injection was 41.6 minutes (20.9), with a range of 7 to 132 minutes. Linear regression identified a significant (P<0.05) difference according to clinic [ranging from 19.4 min (6.5) to 57.5 min (20.2)] and number of family members in the appointment [ranging from 40.6 min (21.0) for an appointment in the index child only to 50 min (14.3) for an appointment in the index child and 2 other family members]. Contrary to healthcare provider perceptions, the timing of outpatient childhood vaccine appointments allows for the inclusion of pain management interventions. Efforts should now focus on educating healthcare providers and parents about the value of pain management and how to implement evidence-based strategies.

Photovoltaic-Powered Vaccine Refrigerator: Freezer Systems Field Test Results

NASA Technical Reports Server (NTRS)

Ratajczak, A. F.

1985-01-01

A project to develop and field test photovoltaic-powered refrigerator/freezers suitable for vaccine storage was undertaken. Three refrigerator/freezers were qualified; one by Solar Power Corp. and two by Solvolt. Follow-on contracts were awarded for 19 field test systems and for 10 field test systems. A total of 29 systems were installed in 24 countries between October 1981 and October 1984. The project, systems descriptions, installation experiences, performance data for the 22 systems for which field test data was reported, an operational reliability summary, and recommendations relative to system designs and future use of such systems are explained. Performance data indicate that the systems are highly reliable and are capable of maintaining proper vaccine storage temperatures in a wide range of climatological and user environments.

Intussusception after monovalent rotavirus vaccine-United States, Vaccine Adverse Event Reporting System (VAERS), 2008-2014.

PubMed

Haber, Penina; Parashar, Umesh D; Haber, Michael; DeStefano, Frank

2015-09-11

In 2006 and 2008, two new rotavirus vaccines (RotaTeq [RV5] and Rotarix [RV1]) were introduced in the United States. US data on intussusception have been mostly related to RV5, with limited data on RV1. We assessed intussusception events following RV1 reported to the Vaccine Adverse Event Reporting System (VAERS), a US national passive surveillance system, during February 2008-December 2014. We conducted a self-controlled risk interval analysis using Poisson regression to estimate the daily reporting ratio (DRR) of intussusception after the first 2 doses of RV1 comparing average daily reports 3-6 versus 0-2 days after vaccination. We calculated the excess risk of intussusception per 100,000 vaccinations based on DRRs and background rates of intussusception. Sensitivity analyses were conducted to assess effects of differential reporting completeness and inaccuracy of baseline rates. VAERS received 108 confirmed insusceptible reports after RV1. A significant clustering was observed on days 3-8 after does1 (p=0.001) and days 2-7 after dose 2 (p=0.001). The DRR comparing the 3-6 day and the 0-2 day periods after RV1 dose 1 was 7.5 (95% CI=2.3, 24.6), translating to an excess risk of 1.6 (95% CI=0.3, 5.8) per 100,000 vaccinations. The DRR was elevated but not significant after dose 2 (2.4 [95% CI=0.8,7.5]). The excess risk ranged from 1.2 to 2.8 per 100,000 in sensitivity analysis. We observed a significant increased risk of intussusception 3-6 days after dose 1 of RV1. The estimated small number of intussusception cases attributable to RV1 is outweighed by the benefits of rotavirus vaccination. Published by Elsevier Ltd.

Vaccines and the infant's immune system--what nurses need to know.

PubMed

Heurter, Helen; Langman, Eileen

2005-01-01

Vaccines prevent serious infections by stimulating the immune system to identify and destroy invading organisms rapidly before they have a chance to cause disease. Armed with the scientific facts to refute current misconceptions surrounding vaccines and the infant's immune system, nurses can provide parents with the answers they need.

Beyond new vaccine introduction: the uptake of pneumococcal conjugate vaccine in the African Region.

PubMed

Olayinka, Folake; Ewald, Leah; Steinglass, Robert

2017-01-01

The number of vaccines available to low-income countries has increased dramatically over the last decade. Overall infant immunization coverage in the WHO African region has stagnated in the past few years while countries' ability to maintain high immunization coverage rates following introduction of new vaccines has been uneven. This case study examines post-introduction coverage among African countries that introduced PCV between 2008 and 2013 and the factors affecting Pneumococcal Conjugate Vaccine (PCV) introduction. Nearly one-third of countries did not achieve 80% infant PCV3 coverage by two years post-introduction and 58% of countries experienced a decline in coverage between post introduction years two and four. Major factors affecting coverage rates included introduction without adequate preparation, insufficient supply chain capacity and management, poor communication between organizations and with the public, and data collection systems that were insufficient to meet information needs. Deliberately addressing these issues as well as longstanding weaknesses during new vaccine introduction can strengthen the immunization and broader health system. Further study is required to identify and address factors that affect maintenance of high coverage following introduction of new vaccines in the African region. Immunization with PCV is one of the most important interventions protecting against pneumonia, the second leading cause of death for children under five globally.

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

PubMed

Bragazzi, Nicola Luigi; Watad, Abdulla; Sharif, Kassem; Adawi, Mohammad; Aljadeff, Gali; Amital, Howard; Shoenfeld, Yehuda

2017-10-01

Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease. In SLE, immune system dysfunction is postulated to result by virtue of the disease itself as well as by the impact of treatment modalities employed. A myriad of immune dysregulations occur including complement system dysfunction among others. Infectious agents are known to complicate the disease course in close to 25-45% of SLE patients. Areas covered: In this review a discussion of the immunogenicity and safety of viral and bacterial vaccinations in SLE was performed. The search included ISI Web of Science (WoS), Scopus, MEDLINE/PubMed, Google-Scholar, DOAJ, EbscoHOST, Scirus, Science Direct, Cochrane Library and ProQuest. Proper string made up of a key-words including 'SLE', 'vaccination', 'safety' and 'efficacy' was used. Expert commentary: Vaccination of SLE patients is proven to be immunogenic. Concerns regarding vaccine safety are postulated, yet no direct relationship between vaccination and disease exacerbation were established. While live virus vaccines are generally contraindicated in immunosuppressive states, generally live attenuated vaccinations are recommended in SLE patients on a case-to-case basis. In SLE patients, clinical parameters such as vaccination during disease exacerbations have not been intensively studied and therefore while apparently safe, vaccination is generally recommended while disease is quiescent.

A Statewide System for Improving Influenza Vaccination Rates in Hospital Employees

PubMed Central

Polgreen, Philip M.; Polgreen, Linnea A.; Evans, Thomas; Helms, Charles

2010-01-01

OBJECTIVE To describe and report the progress of a provider-initiated approach to increase influenza immunization rates for healthcare workers. DESIGN Observational study. SETTING The State of Iowa. SUBJECTS Acute care hospitals in Iowa. METHODS Hospitals reported rates of employee influenza vaccination to a provider-based collaborative during 2 influenza seasons (2006–2007 and 2007–2008). Hospital characteristics related to higher vaccination rates were examined. RESULTS One hundred (87.0%) of 115 Iowa hospitals and/or health systems participated in season 1; individual hospital vaccination rates ranged from 43.5% to 99.2% (mean, 72.4%; median, 73.1%). In season 2, 115 (100%) of 115 Iowa hospitals and/or health systems participated. Individual hospital vaccination rates ranged from 53.6% to 100% (mean, 79.5%; median, 82.0%). In both seasons, urban and large hospitals had vaccination rates that were 6.3% to 7.6% lower than those of hospitals in other locations. Hospitals that used declination statements had influenza vaccination rates 12.6% higher than hospitals that did not use declination statements in season 2. CONCLUSION The initial vaccination rates were high for healthcare workers in Iowa, especially in smaller rural hospitals, and rates increased during season 2. The successful voluntary approach for reporting influenza vaccination rates that we describe provides an efficient platform for collecting and disseminating other statewide measures of healthcare quality. PMID:19327039

A statewide system for improving influenza vaccination rates in hospital employees.

PubMed

Polgreen, Philip M; Polgreen, Linnea A; Evans, Thomas; Helms, Charles

2009-05-01

To describe and report the progress of a provider-initiated approach to increase influenza immunization rates for healthcare workers. Observational study. The State of Iowa. Acute care hospitals in Iowa. Hospitals reported rates of employee influenza vaccination to a provider-based collaborative during 2 influenza seasons (2006-2007 and 2007-2008). Hospital characteristics related to higher vaccination rates were examined. One hundred (87.0%) of 115 Iowa hospitals and/or health systems participated in season 1; individual hospital vaccination rates ranged from 43.5% to 99.2% (mean, 72.4%; median, 73.1%). In season 2, 115 (100%) of 115 Iowa hospitals and/or health systems participated. Individual hospital vaccination rates ranged from 53.6% to 100% (mean, 79.5%; median, 82.0%). In both seasons, urban and large hospitals had vaccination rates that were 6.3% to 7.6% lower than those of hospitals in other locations. Hospitals that used declination statements had influenza vaccination rates 12.6% higher than hospitals that did not use declination statements in season 2. The initial vaccination rates were high for healthcare workers in Iowa, especially in smaller rural hospitals, and rates increased during season 2. The successful voluntary approach for reporting influenza vaccination rates that we describe provides an efficient platform for collecting and disseminating other statewide measures of healthcare quality.

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

PubMed

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

2011-09-22

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

Assessing PCV2 antibodies in field pigs vaccinated with different porcine circovirus 2 vaccines using two commercial ELISA systems.

PubMed

Shin, Min-Kyoung; Yoon, Seung Hyun; Kim, Myung Hwui; Lyoo, Young Soo; Suh, Seung Won; Yoo, Han Sang

2015-01-01

Porcine circovirus type 2 (PCV2) is the primary causative agent for post-weaning, multisystemic, wasting syndrome. Consequently, serologic detection of and vaccination against PCV2 are important for the swine industry. Among several serological tests, the enzyme-linked immunosorbent assay (ELISA) is commonly used to measure anti-PCV2 antibody levels. In the present study, we used two commercial ELISA systems to comparatively evaluate anti-PCV2 antibodies in field pigs treated with three different PCV2 vaccines. Among a total of 517 serum samples, the results of the two ELISAs were fully concordant for 365 positive and 42 negative samples, indicating 78.7% agreement. In addition, the Pearson coefficient (0.636) indicated a moderate correlation between data from the two ELISAs. Results from the farms with pigs vaccinated with the three different PCV2 vaccines demonstrated that most of the vaccinated animals underwent seroconversion. However, the increase and duration of antibody titers varied depending on the vaccine, the presence of maternal antibodies, and the vaccination program. PCV2 serologic status and anti-PCV2 antibody levels of herds from this study could be utilized to determine the best timing for vaccination and assessing vaccination compliance.

Management of infants born to women infected with hepatitis B in the military healthcare system.

PubMed

Sainato, Rebecca J; Simmons, Elizabeth G; Muench, Dawn F; Burnett, Mark W; Braun, LoRanée

2013-08-28

Hepatitis B virus (HBV) is endemic worldwide. Given significant rates of infectivity, all infants born to Hepatitis B surface antigen positive mothers need to receive treatment at birth, immunization and post-vaccination serologic testing. However, not all infants complete these requirements. We performed a retrospective review of the management of infants born to Hepatitis B infected mothers at two large military hospitals in the United States that use a global electronic medical record to track patient results. We then compared these results to those recently published by the National Perinatal Hepatitis B Prevention Program (PHBPP), which does not include hospitals in the United States Military Healthcare System. Our results show that although all infants were managed appropriately at birth and immunization rates were very high, post vaccination follow-up testing rates were much lower than those seen in centers participating in the PHBPP. The rates of post vaccination serological testing were significantly higher for infants born to Hepatitis B e antigen positive mothers and those referred to a pediatric infectious disease specialist. Despite use of a global electronic medical record in the United States Military Healthcare System, management of HBV-exposed infants does not always follow recommended guidelines. These infants could benefit from a more systematic method of follow-up, similar to the PHBPP, to ensure HBV serologic testing is obtained after the vaccination series is complete.

European Vaccine Initiative: lessons from developing malaria vaccines.

PubMed

Geels, Mark J; Imoukhuede, Egeruan B; Imbault, Nathalie; van Schooten, Harry; McWade, Terry; Troye-Blomberg, Marita; Dobbelaer, Roland; Craig, Alister G; Leroy, Odile

2011-12-01

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.

Learning immunology from the yellow fever vaccine: innate immunity to systems vaccinology.

PubMed

Pulendran, Bali

2009-10-01

Despite their great success, we understand little about how effective vaccines stimulate protective immune responses. Two recent developments promise to yield such understanding: the appreciation of the crucial role of the innate immune system in sensing microorganisms and tuning immune responses, and advances in systems biology. Here I review how these developments are yielding insights into the mechanism of action of the yellow fever vaccine, one of the most successful vaccines ever developed, and the broader implications for vaccinology.

Sustainable vaccine development: a vaccine manufacturer's perspective.

PubMed

Rappuoli, Rino; Hanon, Emmanuel

2018-05-08

Vaccination remains the most cost-effective public health intervention after clean water, and the benefits impressively outweigh the costs. The efforts needed to fulfill the steadily growing demands for next-generation and novel vaccines designed for emerging pathogens and new indications are only realizable in a sustainable business model. Vaccine development can be fast-tracked through strengthening international collaborations, and the continuous innovation of technologies to accelerate their design, development, and manufacturing. However, these processes should be supported by a balanced project portfolio, and by managing sustainable vaccine procurement strategies for different types of markets. Collectively this will allow a gradual shift to a more streamlined and profitable vaccine production, which can significantly contribute to the worldwide effort to shape global health. Copyright © 2018 GlaxoSmithKine Biologicals SA. Published by Elsevier Ltd.. All rights reserved.

Gaps in vaccine financing for underinsured children in the United States.

PubMed

Lee, Grace M; Santoli, Jeanne M; Hannan, Claire; Messonnier, Mark L; Sabin, James E; Rusinak, Donna; Gay, Charlene; Lett, Susan M; Lieu, Tracy A

2007-08-08

The number of new vaccines recommended for children and adolescents has nearly doubled during the past 5 years, and the cost of fully vaccinating a child has increased dramatically in the past decade. Anecdotal reports from state policy makers and clinicians suggest that new gaps have arisen in financial coverage of vaccines for children who are underinsured (ie, have private insurance that does not cover all recommended vaccines). In 2000, approximately 14% of children were underinsured for vaccines in the United States. To describe variation among states in the provision of new vaccines to underinsured children and to identify barriers to state purchase and distribution of new vaccines. A 2-phase mixed-methods study of state immunization program managers in the United States. The first phase included 1-hour qualitative telephone interviews conducted from November to December 2005 with 9 program managers chosen to represent different state vaccine financing policies. The second phase incorporated findings from phase 1 to develop a national telephone and paper-based survey of state immunization program managers that was conducted from January to June 2006. Percentage of states in which underinsured children are unable to receive publicly purchased vaccines in the private or public sectors. Immunization program managers from 48 states (96%) participated in the study. Underinsured children were not eligible to receive publicly purchased meningococcal conjugate or pneumococcal conjugate vaccines in the private sector in 70% and 50% of states, respectively, or in the public sector in 40% and 17% of states, respectively. Due to limited financing for new vaccines, 10 states changed their policies for provision of publicly purchased vaccines between 2004 and early 2006 to restrict access to selected new vaccines for underinsured children. The most commonly cited barriers to implementation in underinsured children were lack of sufficient federal and state funding to

Development of a Salmonella cross-protective vaccine for food animal production systems.

PubMed

Heithoff, Douglas M; House, John K; Thomson, Peter C; Mahan, Michael J

2015-01-01

Intensive livestock production is associated with increased Salmonella exposure, transmission, animal disease, and contamination of food and water supplies. Modified live Salmonella enterica vaccines that lack a functional DNA adenine methylase (Dam) confer cross-protection to a diversity of salmonellae in experimental models of murine, avian, ovine, and bovine models of salmonellosis. However, the commercial success of any vaccine is dependent upon the therapeutic index, the ratio of safety/efficacy. Herein, secondary virulence-attenuating mutations targeted to genes involved in intracellular and/or systemic survival were introduced into Salmonella dam vaccines to screen for vaccine candidates that were safe in the animal and the environment, while maintaining the capacity to confer cross-protective immunity to pathogenic salmonellae serotypes. Salmonella dam mgtC, dam sifA, and dam spvB vaccine strains exhibited significantly improved vaccine safety as evidenced by the failure to give rise to virulent revertants during the infective process, contrary to the parental Salmonella dam vaccine. Further, these vaccines exhibited a low grade persistence in host tissues that was associated with reduced vaccine shedding, reduced environmental persistence, and induction of cross-protective immunity to pathogenic serotypes derived from infected livestock. These data indicate that Salmonella dam double mutant vaccines are suitable for commercial applications against salmonellosis in livestock production systems. Reducing pre-harvest salmonellae load through vaccination will promote the health and productivity of livestock and reduce contamination of livestock-derived food products, while enhancing overall food safety. Copyright © 2014 Elsevier Ltd. All rights reserved.

Multifunctional particle-constituted microneedle arrays as cutaneous or mucosal vaccine adjuvant-delivery systems

PubMed Central

Wang, Xueting; Wang, Ning; Li, Ning; Zhen, Yuanyuan; Wang, Ting

2016-01-01

ABSTRACT To overcome drawbacks of current injection vaccines, such as causing needle phobia, needing health professionals for inoculation, and generating dangerous sharps wastes, researchers have designed novel vaccines that are combined with various microneedle arrays (MAs), in particular, with the multifunctional particle-constructed MAs (MPMAs). MPMAs prove able to enhance vaccine stability through incorporating vaccine ingredients in the carrier, and can be painlessly inoculated by minimally trained workers or by self-administration, leaving behind no metal needle pollution while eliciting robust systemic and mucosal immunity to antigens, thanks to delivering vaccines to cutaneous or mucosal compartments enriched in professional antigen-presenting cells (APCs). Especially, MPMAs can be easily integrated with functional molecules fulfilling targeting vaccine delivery or controlling immune response toward a Th1 or Th2 pathway to generate desired immunity against pathogens. Herein, we introduce the latest research and development of various MPMAs which are a novel but promising vaccine adjuvant delivery system (VADS). PMID:27159879

Vaccine profile of herpes zoster (HZ/su) subunit vaccine.

PubMed

Cunningham, Anthony L; Heineman, Thomas

2017-07-01

Herpes zoster (HZ) causes an often severe and painful rash in older people and may be complicated by prolonged pain (postherpetic neuralgia; PHN) and by dissemination in immune-compromised patients. HZ results from reactivation of latent varicella-zoster virus (VZV) infection, often associated with age-related or other causes of decreased T cell immunity. A live attenuated vaccine boosts this immunity and provides partial protection against HZ, but this decreases with age and declines over 8 years. Areas covered: A new HZ subunit (HZ/su) vaccine combines a key surface VZV glycoprotein (E) with a T cell-boosting adjuvant system (AS01 B ) and is administered by two intramuscular injections two months apart. Expert commentary: HZ/su showed excellent efficacy of ~90% in immunocompetent adults ≥50 and ≥70 years of age, respectively, in the ZOE-50 and ZOE-70 phase III controlled trials. Efficacy was unaffected by advancing age and persisted for >3 years. Approximately 9.5% of subjects had severe, but transient (1-2 days) injection site pain, swelling or redness. Compliance with both vaccine doses was high (95%). The vaccine will have a major impact on HZ management. Phase I-II trials showed safety and immunogenicity in severely immunocompromised patients. Phase III trial results are expected soon.

The origins of the vaccine cold chain and a glimpse of the future.

PubMed

Lloyd, John; Cheyne, James

2017-04-19

International efforts to eradicate smallpox in the 1960s and 1970s provided the foundation for efforts to expand immunization programmes, including work to develop immunization supply chains. The need to create a reliable system to keep vaccines cold during the lengthy journey from the manufacturer to the point of use, even in remote areas, was a crucial concern during the early days of the Expanded Programme on Immunization. The vaccine cold chain was deliberately separated from other medical distribution systems to assure timely access to and control of vaccines and injection materials. The story of the early development of the vaccine cold chain shows how a number of challenges were overcome with technological and human resource solutions. For example, the lack of methods to monitor exposure of vaccines to heat during transport and storage led to many innovations, including temperature-sensitive vaccine vial monitors and better methods to record and communicate temperatures in vaccine stores. The need for appropriate equipment to store and transport vaccines in tropical developing countries led to innovations in refrigeration equipment as well as the introduction and widespread adoption of novel high performance vaccine cold-boxes and carriers. New technologies also helped to make injection safer. Underlying this work on technologies and equipment was a major effort to develop the human resources required to manage and implement the immunization supply chain. This included creating foundational policies and a management infrastructure; providing training for managers, health workers, technicians, and others. The vaccine cold chain has contributed to one of the world's public health success stories and provides three priority lessons for future: the vaccine supply chain needs to be integrated with other public health supplies, re-designed for efficiency and effectiveness and work is needed in the longer term to eliminate the need for refrigeration in the supply

Seasonal influenza vaccination of healthcare employees: results of a 4-year campaign.

PubMed

Hirsch, Pamela; Hodgson, Michael; Davey, Victoria

2011-05-01

To document successful substantial increases in healthcare worker influenza vaccination rates and to identify reasons for success and failure. (1) Four-year longitudinal characterization of facility vaccination rates, (2) Web-based facility-level questionnaire for influenza coordinators to identify success factors in year 3, and (3) semistructured telephone interviews of influenza coordinators at facilities with substantial increases or declines in year 4. National single-payer hospital (healthcare) system with 153 hospitals in 5 levels of complexity. Facility leadership staff. (1) Vaccination data collected from management sources (doses from pharmacies, denominator data from payrolls); (2) a Web-based survey aligned with a previously administered instrument (Wisconsin Health Department), piloted in-house, modified to reflect national strategies and improvements; and (3) semistructured telephone interviews with influenza coordinators at facilities that improved or worsened by more than 20% between the 2007-2008 and 2008-2009 influenza seasons. Vaccination acceptance rates improved from 45% of healthcare workers in 2005-2006 to 66.5% in 2008-2009. Facilities with lower complexity had higher vaccination rates. No individual factors were associated with improved performance. Sustained management attention can lead to improvements in healthcare worker influenza vaccination rates. Wavering of attention, though, may lead to rapid loss of effectiveness. Declination statements in this system did not contribute to vaccine acceptance.

Systemic allergic reactions to gelatin included in vaccines as a stabilizer.

PubMed

Sakaguchi, M; Inouye, S

2000-10-01

Most of the children who showed systemic immediate-type reactions, including anaphylactic shock, to measles, mumps, rubella, and varicella vaccines had IgE antibodies to gelatin; thus we suspected that the allergic symptoms are caused by gelatin antigen, which is usually included in these live-virus vaccines as a stabilizer. We hypothesized that the anti-gelatin IgE is elicited by immunization with DTaP (diphtheria-tetanus-acellular pertussis) vaccines, which contained a small amount of gelatin as a spillover protein after purification of pertussis toxin. To test this hypothesis, we conducted a case-control study to determine whether children with anti-gelatin IgE had received gelatin-containing DTaP vaccines, and it was indeed found that all such children in the study had immunization histories that included the gelatin-containing DTaP vaccines. Based on these findings, the vaccine manufacturers had removed gelatin from all the DTaP and live-virus vaccines produced in Japan by 2000.

Emergency medicine tools to manage smallpox (vaccinia) vaccination complications: clinical practice guideline and policies and procedures.

PubMed

Thorne, Craig D; Hirshon, Jon Mark; Himes, Carrie D; McDiarmid, Melissa A

2003-11-01

In December 2002, the federal government began a program to immunize approximately 500000 civilian public health and health care workers with smallpox (vaccinia) vaccine as a part of our pre-event defense against bioterrorism. First responders will likely follow, and the general US population might be offered vaccination in the next 1 to 2 years. Recent reports that suggest the possible association of the vaccine to adverse cardiac events (including deaths), liability concerns for hospitals, and the availability of compensation for workers with vaccine complications have significantly reduced voluntary participation. Vaccinees might experience robust primary takes or serious adverse events, including viral or even bacterial cellulitides, encephalitis, progressive skin destruction, and other life-threatening complications. With the increasing prevalence of immune suppression from both diseases and immunosuppressive medications, complications might be seen in higher frequency than previously reported. Emergency medicine providers and staff must become familiar with clinical presentations and management of vaccine complications. In addition, policies and procedures must be developed to prevent unimmunized providers from inadvertently contacting the active vaccination sites of their patients and, if the providers themselves have active vaccination sites, to protect their patients and their own families.

Food allergy to gelatin in children with systemic immediate-type reactions, including anaphylaxis, to vaccines.

PubMed

Sakaguchi, M; Nakayama, T; Inouye, S

1996-12-01

Anaphylaxis to measles-mumps-rubella vaccines has been reported. We have suspected that most such reactions are caused by gelatin contained in the vaccines. To confirm the relation between systemic allergic reactions to vaccines and the presence of anti-gelatin IgE, we measured anti-gelatin IgE in children who demonstrated allergy to gelatin-containing vaccines. Furthermore, to clarify the relation between allergic reactions to gelatin in vaccines and foods, we surveyed the occurrence of allergic reactions to gelatin-containing foods in the same children. Serum samples were taken from 26 children who had systemic immediate-type reactions, including anaphylactic shock, to vaccines and the same number of children without allergic reactions. Specific IgE to gelatin in these samples was measured. We then surveyed whether these children had allergic reactions to gelatin-containing foods before and after vaccination. Twenty-four of the 26 children with allergic reactions to vaccines had anti-gelatin IgE ranging from 1.2 to 250 Ua/ml. Seven had allergic reactions on ingestion of gelatin-containing foods. Of these, two had reactions before vaccination, and five had reactions after vaccination. All the control children without allergic reactions to vaccines had no anti-gelatin IgE. We reconfirmed a strong relationship between systemic immediate-type allergic reactions, including anaphylaxis, to vaccines and the presence of specific IgE to gelatin. Moreover, some of the children also had allergic reactions to food gelatin before or after vaccination.

A Comparative Study on the Lot Release Systems for Vaccines as of 2016.

PubMed

Fujita, Kentaro; Naito, Seishiro; Ochiai, Masaki; Konda, Toshifumi; Kato, Atsushi

2017-09-25

Many countries have already established their own vaccine lot release system that is designed for each country's situation: while the World Health Organization promotes for the convergence of these regulatory systems so that vaccines of assured quality are provided globally. We conducted a questionnaire-based investigation of the lot release systems for vaccines in 7 countries and 2 regions. We found that a review of the summary protocol by the National Regulatory Authorities was commonly applied for the independent lot release of vaccines, however, we also noted some diversity between countries, especially in regard to the testing policy. Some countries and regions, including Japan, regularly tested every lot of vaccines, whereas the frequency of these tests was reduced in other countries and regions as determined based on the risk assessment of these products. Test items selected for the lot release varied among the countries or regions investigated, although there was a tendency to prioritize the potency tests. An understanding of the lot release policy may contribute to improving and harmonizing the lot release system globally in the future.

Use of contingency management incentives to improve completion of hepatitis B vaccination in people undergoing treatment for heroin dependence: a cluster randomised trial.

PubMed

Weaver, Tim; Metrebian, Nicola; Hellier, Jennifer; Pilling, Stephen; Charles, Vikki; Little, Nicholas; Poovendran, Dilkushi; Mitcheson, Luke; Ryan, Frank; Bowden-Jones, Owen; Dunn, John; Glasper, Anthony; Finch, Emily; Strang, John

2014-07-12

Poor adherence to treatment diminishes its individual and public health benefit. Financial incentives, provided on the condition of treatment attendance, could address this problem. Injecting drug users are a high-risk group for hepatitis B virus (HBV) infection and transmission, but adherence to vaccination programmes is poor. We aimed to assess whether contingency management delivered in routine clinical practice increased the completion of HBV vaccination in individuals receiving opioid substitution therapy. In our cluster randomised controlled trial, we enrolled participants at 12 National Health Service drug treatment services in the UK that provided opioid substitution therapy and nurse-led HBV vaccination with a super-accelerated schedule (vaccination days 0, 7, and 21). Clusters were randomly allocated 1:1:1 to provide vaccination without incentive (treatment as usual), with fixed value contingency management (three £10 vouchers), or escalating value contingency management (£5, £10, and £15 vouchers). Both contingency management schedules rewarded on-time attendance at appointments. The primary outcome was completion of clinically appropriate HBV vaccination within 28 days. We also did sensitivity analyses that examined vaccination completion with full adherence to appointment times and within a 3 month window. The trial is registered with Current Controlled Trials, number ISRCTN72794493. Between March 16, 2011, and April 26, 2012, we enrolled 210 eligible participants. Compared with six (9%) of 67 participants treated as usual, 35 (45%) of 78 participants in the fixed value contingency management group met the primary outcome measure (odds ratio 12·1, 95% CI 3·7-39·9; p<0·0001), as did 32 (49%) of 65 participants in the escalating value contingency management group (14·0, 4·2-46·2; p<0·0001). These differences remained significant with sensitivity analyses. Modest financial incentives delivered in routine clinical practice significantly improve

Vaccine Hesitancy.

PubMed

Jacobson, Robert M; St Sauver, Jennifer L; Finney Rutten, Lila J

2015-11-01

Vaccine refusal received a lot of press with the 2015 Disneyland measles outbreak, but vaccine refusal is only a fraction of a much larger problem of vaccine delay and hesitancy. Opposition to vaccination dates back to the 1800 s, Edward Jenner, and the first vaccine ever. It has never gone away despite the public's growing scientific sophistication. A variety of factors contribute to modern vaccine hesitancy, including the layperson's heuristic thinking when it comes to balancing risks and benefits as well as a number of other features of vaccination, including falling victim to its own success. Vaccine hesitancy is pervasive, affecting a quarter to a third of US parents. Clinicians report that they routinely receive requests to delay vaccines and that they routinely acquiesce. Vaccine rates vary by state and locale and by specific vaccine, and vaccine hesitancy results in personal risk and in the failure to achieve or sustain herd immunity to protect others who have contraindications to the vaccine or fail to generate immunity to the vaccine. Clinicians should adopt a variety of practices to combat vaccine hesitancy, including a variety of population health management approaches that go beyond the usual call to educate patients, clinicians, and the public. Strategies include using every visit to vaccinate, the creation of standing orders or nursing protocols to provide vaccination without clinical encounters, and adopting the practice of stating clear recommendations. Up-to-date, trusted resources exist to support clinicians' efforts in adopting these approaches to reduce vaccine hesitancy and its impact. Copyright © 2015 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Vaccination policies and programs: the federal government's role in making the system work.

PubMed

Schwartz, B; Orenstein, W A

2001-12-01

Government agencies play a key role, from preclinical development to postlicensure monitoring, in making vaccinations one of the leading public health interventions. Important steps in this process include development and testing of vaccine antigens, evaluation of clinical and manufacturing data leading to licensure, formulation of recommendations, vaccine purchase, defining strategies to improve coverage, compensation of those injured by vaccine adverse reactions, and monitoring vaccine impact and safety. Using examples of newly recommended vaccines, this article describes the infrastructure that underlies a safe and effective program and highlights some of the opportunities and threats likely to impact the system in coming years.

Dissecting polyclonal vaccine-induced humoral immunity against HIV using Systems Serology

PubMed Central

Chung, Amy W.; Kumar, Manu P.; Arnold, Kelly B.; Yu, Wen Han; Schoen, Matthew K.; Dunphy, Laura J.; Suscovich, Todd J.; Frahm, Nicole; Linde, Caitlyn; Mahan, Alison E.; Hoffner, Michelle; Streeck, Hendrik; Ackerman, Margaret E.; McElrath, M. Juliana; Schuitemaker, Hanneke; Pau, Maria G.; Baden, Lindsey R.; Kim, Jerome H.; Michael, Nelson L.; Barouch, Dan H.; Lauffenburger, Douglas A.; Alter, Galit

2017-01-01

While antibody titers and neutralization are considered the gold standard for the selection of successful vaccines, these parameters are often inadequate predictors of protective immunity. As antibodies mediate an array of extra-neutralizing Fc-functions, when neutralization fails to predict protection, investigating Fc-mediated activity may help identify immunological correlates and mechanism(s) of humoral protection. Here, we used an integrative approach termed Systems Serology to analyze relationships among humoral responses elicited in four HIV vaccine-trials. Each vaccine regimen induced a unique humoral “Fc-fingerprint”. Moreover, analysis of case:control data from the first moderately protective HIV vaccine trial, RV144, pointed to mechanistic insights into immune complex composition that may underlie protective immunity to HIV. Thus, multi-dimensional relational comparisons of vaccine humoral fingerprints offer a unique approach for the evaluation and design of novel vaccines against pathogens for which correlates of protection remain elusive. PMID:26544943

Comprehensive screening for immunodeficiency-associated vaccine-derived poliovirus: an essential oral poliovirus vaccine cessation risk management strategy.

PubMed

Duintjer Tebbens, R J; Thompson, K M

2017-01-01

If the world can successfully control all outbreaks of circulating vaccine-derived poliovirus that may occur soon after global oral poliovirus vaccine (OPV) cessation, then immunodeficiency-associated vaccine-derived polioviruses (iVDPVs) from rare and mostly asymptomatic long-term excretors (defined as ⩾6 months of excretion) will become the main source of potential poliovirus outbreaks for as long as iVDPV excretion continues. Using existing models of global iVDPV prevalence and global long-term poliovirus risk management, we explore the implications of uncertainties related to iVDPV risks, including the ability to identify asymptomatic iVDPV excretors to treat with polio antiviral drugs (PAVDs) and the transmissibility of iVDPVs. The expected benefits of expanded screening to identify and treat long-term iVDPV excretors with PAVDs range from US$0.7 to 1.5 billion with the identification of 25-90% of asymptomatic long-term iVDPV excretors, respectively. However, these estimates depend strongly on assumptions about the transmissibility of iVDPVs and model inputs affecting the global iVDPV prevalence. For example, the expected benefits may decrease to as low as US$260 million with the identification of 90% of asymptomatic iVDPV excretors if iVDPVs behave and transmit like partially reverted viruses instead of fully reverted viruses. Comprehensive screening for iVDPVs will reduce uncertainties and maximize the expected benefits of PAVD use.

[Adverse events self-declaration system and influenza vaccination coverage of healthcare workers in a tertiary hospital].

PubMed

Velasco Munoz, Cesar; Sequera, Víctor-Guillermo; Vilajeliu, Alba; Aldea, Marta; Mena, Guillermo; Quesada, Sebastiana; Varela, Pilar; Olivé, Victoria; Bayas, José M; Trilla, Antoni

2016-02-19

During the influenza vaccination campaign 2011-2012 we established a self-declaration system of adverse events (AEs) in healthcare workers (HCW). The aim of this study is to describe the vaccinated population and analyse vaccination coverage and self-declared AEs after the voluntary flu vaccination in a university hospital in Barcelona. Observational study. We used the HCW immunization record to calculate the vaccination coverage. We collected AEs using a voluntary, anonymous, self-administered survey during the 2011-2012 flu vaccination campaign. We performed a logistic regression model to determine the associated factors to declare AEs. The influenza vaccination coverage in HCW was 30.5% (n=1,507/4,944). We received completed surveys from 358 vaccinated HCW (23.8% of all vaccinated). We registered AEs in 186 respondents to the survey (52.0% of all respondents). Of these, 75.3% (n=140) reported local symptoms after the flu vaccination, 9.7% (n=18) reported systemic symptoms and 15.1% (n=28) both local and systemic symptoms. No serious AEs were self-reported. Female sex and aged under 35 were both factors associated with declaring AEs. Our self-reporting system did not register serious AEs in HCW, resulting in an opportunity to improve HCW trust in flu vaccination. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

Preparation for global introduction of inactivated poliovirus vaccine: safety evidence from the US Vaccine Adverse Event Reporting System, 2000-12.

PubMed

Iqbal, Shahed; Shi, Jing; Seib, Katherine; Lewis, Paige; Moro, Pedro L; Woo, Emily J; Shimabukuro, Tom; Orenstein, Walter A

2015-10-01

Safety data from countries with experience in the use of inactivated poliovirus vaccine (IPV) are important for the global polio eradication strategy to introduce IPV into the immunisation schedules of all countries. In the USA, IPV has been included in the routine immunisation schedule since 1997. We aimed to analyse adverse events after IPV administration reported to the US Vaccine Adverse Event Reporting System (VAERS). We analysed all VAERS data associated with IPV submitted between Jan 1, 2000, and Dec 31, 2012, either as individual or as combination vaccines, for all age and sex groups. We analysed the number and event type (non-serious, non-fatal serious, and death reports) of individual reports, and explored the most commonly coded event terms to describe the adverse event. We classified death reports according to previously published body-system categories (respiratory, cardiovascular, neurological, gastrointestinal, other infectious, and other non-infectious) and reviewed death reports to identify the cause of death. We classified sudden infant death syndrome as a separate cause of death considering previous concerns about sudden infant syndrome after vaccines. We used empirical Bayesian data mining methods to identify disproportionate reporting of adverse events for IPV compared with other vaccines. Additional VAERS data from 1991 to 2000 were analysed to compare the safety profiles of IPV and oral poliovirus vaccine (OPV). Of the 41,792 adverse event reports submitted, 39,568 (95%) were for children younger than 7 years. 38,381 of the reports for children in this age group (97%) were for simultaneous vaccination with IPV and other vaccines (most commonly pneumococcal and acellular pertussis vaccines), whereas standalone IPV vaccines accounted for 0·5% of all reports. 34,880 reports were for non-serious events (88%), 3905 reports were for non-fatal serious events (10%), and 783 reports were death reports (2%). Injection-site erythema was the most

Ancillary study management systems: a review of needs

PubMed Central

2013-01-01

Background The valuable clinical data, specimens, and assay results collected during a primary clinical trial or observational study can enable researchers to answer additional, pressing questions with relatively small investments in new measurements. However, management of such follow-on, “ancillary” studies is complex. It requires coordinating across institutions, sites, repositories, and approval boards, as well as distributing, integrating, and analyzing diverse data types. General-purpose software systems that simplify the management of ancillary studies have not yet been explored in the research literature. Methods We have identified requirements for ancillary study management primarily as part of our ongoing work with a number of large research consortia. These organizations include the Center for HIV/AIDS Vaccine Immunology (CHAVI), the Immune Tolerance Network (ITN), the HIV Vaccine Trials Network (HVTN), the U.S. Military HIV Research Program (MHRP), and the Network for Pancreatic Organ Donors with Diabetes (nPOD). We also consulted with researchers at a range of other disease research organizations regarding their workflows and data management strategies. Lastly, to enhance breadth, we reviewed process documents for ancillary study management from other organizations. Results By exploring characteristics of ancillary studies, we identify differentiating requirements and scenarios for ancillary study management systems (ASMSs). Distinguishing characteristics of ancillary studies may include the collection of additional measurements (particularly new analyses of existing specimens); the initiation of studies by investigators unaffiliated with the original study; cross-protocol data pooling and analysis; pre-existing participant consent; and pre-existing data context and provenance. For an ASMS to address these characteristics, it would need to address both operational requirements (e.g., allocating existing specimens) and data management requirements

Managing prairie dogs by managing plague: a vaccine for the future?

USGS Publications Warehouse

Johnson, Terry B.; Rocke, Tonie E.; Gober, Pete; Van Pelt, Bill E.; Miller, Michael W.; Tripp, Daniel W.; Abbott, Rachel C.; Bergman, David L.

2014-01-01

The Black-footed Ferret Recovery Implementation Team Executive Committee is conducting a project to develop,and (hopefully) eventually implement, a plague vaccination program for prairie dogs. The project is a component of the WesternAssociation of Fish and Wildlife Agencies Grasslands Conservation Initiative. An effective, field-worthy vaccine against plaguecould be the biggest breakthrough in recovery efforts for the black-footed ferret since the 1981 rediscovery of wild ferrets nearMeeteetse, Wyoming. If proven efficacious, the vaccine could help agencies and stakeholder cooperators maintain specificpopulations of prairie dogs at robust levels, thus enhancing range-wide conservation of those species, as well recovery of the ferret,while enabling control of other prairie dog populations to resolve site-specific agricultural and human health concerns. The resultsof laboratory and field-testing in the early stages of developing this vaccine are preliminary but mostly encouraging. A plan forbroad-scale application is being developed for possible use when testing has been completed and (if warranted) the vaccine isregistered for governmental use. An overview of all aspects of the project is discussed.

Availability of quality vaccines: policies of a non-government organization.

PubMed

Poore, P

1992-01-01

The availability of vaccines, or any other health service, depends upon, first, the existence of a reliable system of delivery, and the effective management of this system to reach the target population and, second, the acceptance by parents or guardians of the value of the vaccine in preventing death and disability in young children and their mothers. This system must be fully funded and resourced for the foreseeable future if the service is to be sustainable. Today the major obstacles to effective immunization of young children in developing countries is the inadequate, insecure and unpredictable availability of funds and their management. Unless these problems are addressed and solved, the immunization targets set by the World Health Assembly (WHA) will not be met.

The data management of a phase III efficacy trial of an 11-valent pneumococcal conjugate vaccine and related satellite studies conducted in the Philippines.

PubMed

Sanvictores, Diozele Hazel M; Lucero, Marilla G; Nohynek, Hanna; Tallo, Veronica L; Tanskanen, Antti; Nillos, Leilani T; Williams, Gail

2012-06-07

A large phase III placebo-controlled, randomized efficacy trial of an investigational 11-valent pneumococcal conjugate vaccine against pneumonia in children less than 2 years of age was conducted in the Philippines from July 2000 to December 2004. Clinical data from 12,194 children who were given either study vaccine or placebo was collected from birth up to two years of age for the occurrence of radiologically proven pneumonia as the primary endpoint, and for clinical pneumonia and invasive pneumococcal disease as the secondary endpoints. Several tertiary endpoints were also explored. Along the core trial, several satellite studies on herd immunity, cost-effectiveness of the study vaccine, acute otitis media, and wheezing were conducted. We describe here in detail how the relevant clinical records were managed and how quality control procedures were implemented to ensure that valid data were obtained respectively for the core trial and for the satellite studies. We discuss how the task was achieved, what the challenges were and what might have been done differently. There were several factors that made the task of data management doable and efficient. First, a pre-trial data management system was available. Secondly, local committed statisticians, programmers and support staff were available and partly familiar to clinical trials. Thirdly, the personnel had undergone training during trial and grew with the task they were supposed to do. Thus the knowledge needed to develop and operate clinical data system was fully transferred to local staff. Current Controlled Trials ISRCTN62323832.

Systemic immune response and virus persistence after foot-and-mouth disease virus infection of naïve cattle and cattle vaccinated with a homologous adenovirus-vectored vaccine

DOE PAGES

Eschbaumer, Michael; Stenfeldt, Carolina; Rekant, Steven I.; ...

2016-09-15

In order to investigate host factors associated with the establishment of persistent foot-and-mouth disease virus (FMDV) infection, the systemic response to vaccination and challenge was studied in 47 steers. Eighteen steers that had received a recombinant FMDV A vaccine 2 weeks earlier and 29 non-vaccinated steers were challenged by intra-nasopharyngeal deposition of FMDV A24. For up to 35 days after challenge, host factors including complete blood counts with T lymphocyte subsets, type I/III interferon (IFN) activity, neutralizing and total FMDV-specific antibody titers in serum, as well as antibody-secreting cells (in 6 non-vaccinated animals) were characterized in the context of viralmore » infection dynamics. As a result, vaccination generally induced a strong antibody response. There was a transient peak of FMDV-specific serum IgM in non-vaccinated animals after challenge, while IgM levels in vaccinated animals did not increase further. Both groups had a lasting increase of specific IgG and neutralizing antibody after challenge. Substantial systemic IFN activity in non-vaccinated animals coincided with viremia, and no IFN or viremia was detected in vaccinated animals. After challenge, circulating lymphocytes decreased in non-vaccinated animals, coincident with viremia, IFN activity, and clinical disease, whereas lymphocyte and monocyte counts in vaccinated animals were unaffected by vaccination but transiently increased after challenge. The CD4 +/CD8 + T cell ratio in non-vaccinated animals increased during acute infection, driven by an absolute decrease of CD8 + cells. In conclusion, the incidence of FMDV persistence was 61.5 % in non-vaccinated and 54.5 % in vaccinated animals. Overall, the systemic factors examined were not associated with the FMDV carrier/non-carrier divergence; however, significant differences were identified between responses of non-vaccinated and vaccinated cattle.« less

Systemic immune response and virus persistence after foot-and-mouth disease virus infection of naïve cattle and cattle vaccinated with a homologous adenovirus-vectored vaccine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eschbaumer, Michael; Stenfeldt, Carolina; Rekant, Steven I.

In order to investigate host factors associated with the establishment of persistent foot-and-mouth disease virus (FMDV) infection, the systemic response to vaccination and challenge was studied in 47 steers. Eighteen steers that had received a recombinant FMDV A vaccine 2 weeks earlier and 29 non-vaccinated steers were challenged by intra-nasopharyngeal deposition of FMDV A24. For up to 35 days after challenge, host factors including complete blood counts with T lymphocyte subsets, type I/III interferon (IFN) activity, neutralizing and total FMDV-specific antibody titers in serum, as well as antibody-secreting cells (in 6 non-vaccinated animals) were characterized in the context of viralmore » infection dynamics. As a result, vaccination generally induced a strong antibody response. There was a transient peak of FMDV-specific serum IgM in non-vaccinated animals after challenge, while IgM levels in vaccinated animals did not increase further. Both groups had a lasting increase of specific IgG and neutralizing antibody after challenge. Substantial systemic IFN activity in non-vaccinated animals coincided with viremia, and no IFN or viremia was detected in vaccinated animals. After challenge, circulating lymphocytes decreased in non-vaccinated animals, coincident with viremia, IFN activity, and clinical disease, whereas lymphocyte and monocyte counts in vaccinated animals were unaffected by vaccination but transiently increased after challenge. The CD4 +/CD8 + T cell ratio in non-vaccinated animals increased during acute infection, driven by an absolute decrease of CD8 + cells. In conclusion, the incidence of FMDV persistence was 61.5 % in non-vaccinated and 54.5 % in vaccinated animals. Overall, the systemic factors examined were not associated with the FMDV carrier/non-carrier divergence; however, significant differences were identified between responses of non-vaccinated and vaccinated cattle.« less

Vaccination: a novel strategy for inhibiting the renin-angiotensin-aldosterone system.

PubMed

Gradman, Alan H; Pinto, Rehka

2008-12-01

Immunologic approaches to renin-angiotensin-aldosterone system (RAAS) inhibition have been studied for more than 50 years. In animal models, vaccination against renin was effective but resulted in fatal autoimmune renal disease; vaccines directed at small peptides including angiotensin I and II and a segment of the AT(1) receptor reduced blood pressure (BP) without causing autoimmune disease. In humans, angiotensin I vaccination did not reduce BP. More promising is the AngQb vaccine, which uses an immunization technology involving conjugation of angiotensin II to virus-like particles. In a phase 2 trial, hypertensive patients vaccinated with 300 microg showed a difference of 9.0/4.0 mm Hg from baseline in mean daytime ambulatory BP after 14 weeks (P = 0.015 for systolic BP, P = 0.064 for diastolic BP), and a marked reduction in early morning BP. No serious adverse events were attributed to vaccine administration. Although questions remain regarding efficacy and safety, RAAS immunization represents an innovative and promising approach to hypertension treatment.

Cancer vaccines: the challenge of developing an ideal tumor killing system.

PubMed

Mocellin, Simone

2005-09-01

Despite the evidence that the immune system plays a significant role in controlling tumor growth in natural conditions and in response to therapeutic vaccination, cancer cells can survive their attack as the disease progresses and no vaccination regimen should be currently proposed to patients outside experimental clinical trials. Clinical results show that the immune system can be actively polarized against malignant cells by means of a variety of vaccination strategies, and that in some cases this is associated with tumor regression. This implies that under some unique circumstances, the naturally "dormant" immune effectors can actually be put at work and used as endogenous weapons against malignant cells. Consequently, the main challenge of tumor immunologists appears to lie on the ability of reproducing those conditions in a larger set of patients. The complexity of the immune network and the still enigmatic host-tumor interactions make these tasks at the same time challenging and fascinating. Recent tumor immunology findings are giving new impetus to the development of more effective vaccination strategies and might revolutionize the way of designing the next generation of cancer vaccines. In the near future, the implementation of these insights in the clinical setting and the completion/conduction of comparative randomized phase III trials will allow oncologists to define the actual role of cancer vaccines in the fight against malignancy.

Engineered hybrid spider silk particles as delivery system for peptide vaccines.

PubMed

Lucke, Matthias; Mottas, Inès; Herbst, Tina; Hotz, Christian; Römer, Lin; Schierling, Martina; Herold, Heike M; Slotta, Ute; Spinetti, Thibaud; Scheibel, Thomas; Winter, Gerhard; Bourquin, Carole; Engert, Julia

2018-07-01

The generation of strong T-cell immunity is one of the main challenges for the development of successful vaccines against cancer and major infectious diseases. Here we have engineered spider silk particles as delivery system for a peptide-based vaccination that leads to effective priming of cytotoxic T-cells. The recombinant spider silk protein eADF4(C16) was fused to the antigenic peptide from ovalbumin, either without linker or with a cathepsin cleavable peptide linker. Particles prepared from the hybrid proteins were taken up by dendritic cells, which are essential for T-cell priming, and successfully activated cytotoxic T-cells, without signs of immunotoxicity or unspecific immunostimulatory activity. Upon subcutaneous injection in mice, the particles were taken up by dendritic cells and accumulated in the lymph nodes, where immune responses are generated. Particles from hybrid proteins containing a cathepsin-cleavable linker induced a strong antigen-specific proliferation of cytotoxic T-cells in vivo, even in the absence of a vaccine adjuvant. We thus demonstrate the efficacy of a new vaccine strategy using a protein-based all-in-one vaccination system, where spider silk particles serve as carriers with an incorporated peptide antigen. Our study further suggests that engineered spider silk-based vaccines are extremely stable, easy to manufacture, and readily customizable. Copyright © 2018 Elsevier Ltd. All rights reserved.

Do existing research summaries on health systems match immunisation managers' needs in middle- and low-income countries? Analysis of GAVI health systems strengthening support

PubMed Central

2011-01-01

Background The GAVI Alliance was created in 2000 to increase access to vaccines. More recently, GAVI has supported evidence-based health systems strengthening to overcome barriers to vaccination. Our objectives were: to explore countries' priorities for health systems strengthening; to describe published research summaries for each priority area in relation to their number, quality and relevance; and to describe the use of national data from surveys in identifying barriers to immunisation. Methods From 44 health systems strengthening proposals submitted to GAVI in 2007 and 2008, we analysed the topics identified, the coverage of these topics by existing systematic reviews and the use of nation-wide surveys with vaccination data to justify the needs identified in the proposals. Results Thirty topics were identified and grouped into three thematic areas: health workforce (10 topics); organisation and management (14); and supply, distribution and maintenance (6). We found 51 potentially relevant systematic reviews, although for the topic that appeared most frequently in the proposals ('Health information systems') no review was identified. Thematic and geographic relevance were generally categorised as "high" in 33 (65%) and 25 (49%) reviews, respectively, but few reviews were categorised as "highly relevant for policy" (7 reviews, 14%). With regard to methodological quality, 14 reviews (27%) were categorised as "high". The number of topics that were addressed by at least one high quality systematic review was: seven of the 10 topics in the 'health workforce' thematic area; six of the 14 topics in the area of 'organisation and management'; and none of the topics in the thematic area of 'supply, distribution and maintenance'. Only twelve of the 39 countries with available national surveys referred to them in their proposals. Conclusion Relevant, high quality research summaries were found for few of the topics identified by managers. Few proposals used national surveys

Vaccine adverse event text mining system for extracting features from vaccine safety reports.

PubMed

Botsis, Taxiarchis; Buttolph, Thomas; Nguyen, Michael D; Winiecki, Scott; Woo, Emily Jane; Ball, Robert

2012-01-01

To develop and evaluate a text mining system for extracting key clinical features from vaccine adverse event reporting system (VAERS) narratives to aid in the automated review of adverse event reports. Based upon clinical significance to VAERS reviewing physicians, we defined the primary (diagnosis and cause of death) and secondary features (eg, symptoms) for extraction. We built a novel vaccine adverse event text mining (VaeTM) system based on a semantic text mining strategy. The performance of VaeTM was evaluated using a total of 300 VAERS reports in three sequential evaluations of 100 reports each. Moreover, we evaluated the VaeTM contribution to case classification; an information retrieval-based approach was used for the identification of anaphylaxis cases in a set of reports and was compared with two other methods: a dedicated text classifier and an online tool. The performance metrics of VaeTM were text mining metrics: recall, precision and F-measure. We also conducted a qualitative difference analysis and calculated sensitivity and specificity for classification of anaphylaxis cases based on the above three approaches. VaeTM performed best in extracting diagnosis, second level diagnosis, drug, vaccine, and lot number features (lenient F-measure in the third evaluation: 0.897, 0.817, 0.858, 0.874, and 0.914, respectively). In terms of case classification, high sensitivity was achieved (83.1%); this was equal and better compared to the text classifier (83.1%) and the online tool (40.7%), respectively. Our VaeTM implementation of a semantic text mining strategy shows promise in providing accurate and efficient extraction of key features from VAERS narratives.

Responding to Vaccine Safety Signals during Pandemic Influenza: A Modeling Study

PubMed Central

Maro, Judith C.; Fryback, Dennis G.; Lieu, Tracy A.; Lee, Grace M.; Martin, David B.

2014-01-01

Background Managing emerging vaccine safety signals during an influenza pandemic is challenging. Federal regulators must balance vaccine risks against benefits while maintaining public confidence in the public health system. Methods We developed a multi-criteria decision analysis model to explore regulatory decision-making in the context of emerging vaccine safety signals during a pandemic. We simulated vaccine safety surveillance system capabilities and used an age-structured compartmental model to develop potential pandemic scenarios. We used an expert-derived multi-attribute utility function to evaluate potential regulatory responses by combining four outcome measures into a single measure of interest: 1) expected vaccination benefit from averted influenza; 2) expected vaccination risk from vaccine-associated febrile seizures; 3) expected vaccination risk from vaccine-associated Guillain-Barre Syndrome; and 4) expected change in vaccine-seeking behavior in future influenza seasons. Results Over multiple scenarios, risk communication, with or without suspension of vaccination of high-risk persons, were the consistently preferred regulatory responses over no action or general suspension when safety signals were detected during a pandemic influenza. On average, the expert panel valued near-term vaccine-related outcomes relative to long-term projected outcomes by 3∶1. However, when decision-makers had minimal ability to influence near-term outcomes, the response was selected primarily by projected impacts on future vaccine-seeking behavior. Conclusions The selected regulatory response depends on how quickly a vaccine safety signal is identified relative to the peak of the pandemic and the initiation of vaccination. Our analysis suggested two areas for future investment: efforts to improve the size and timeliness of the surveillance system and behavioral research to understand changes in vaccine-seeking behavior. PMID:25536228

Feasibility of using global system for mobile communication (GSM)-based tracking for vaccinators to improve oral poliomyelitis vaccine campaign coverage in rural Pakistan.

PubMed

Chandir, Subhash; Dharma, Vijay Kumar; Siddiqi, Danya Arif; Khan, Aamir Javed

2017-09-05

Despite multiple rounds of immunization campaigns, it has not been possible to achieve optimum immunization coverage for poliovirus in Pakistan. Supplementary activities to improve coverage of immunization, such as door-to-door campaigns are constrained by several factors including inaccurate hand-drawn maps and a lack of means to objectively monitor field teams in real time, resulting in suboptimal vaccine coverage during campaigns. Global System for Mobile Communications (GSM) - based tracking of mobile subscriber identity modules (SIMs) of vaccinators provides a low-cost solution to identify missed areas and ensure effective immunization coverage. We conducted a pilot study to investigate the feasibility of using GSM technology to track vaccinators through observing indicators including acceptability, ease of implementation, costs and scalability as well as the likelihood of ownership by District Health Officials. The real-time location of the field teams was displayed on a GSM tracking web dashboard accessible by supervisors and managers for effective monitoring of workforce attendance including 'time in-time out', and discerning if all target areas - specifically remote and high-risk locations - had been reached. Direct access to this information by supervisors eliminated the possibility of data fudging and inaccurate reporting by workers regarding their mobility. The tracking cost per vaccinator was USD 0.26/month. Our study shows that GSM-based tracking is potentially a cost-efficient approach, results in better monitoring and accountability, is scalable and provides the potential for improved geographic coverage of health services. Copyright © 2017 Elsevier Ltd. All rights reserved.

Good vaccination practice: it all starts with a good vaccine storage temperature.

PubMed

Vangroenweghe, Frédéric

2017-01-01

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

Virus-like particles as a vaccine delivery system: myths and facts.

PubMed

Roy, Polly; Noad, Rob

2009-01-01

Vaccines against viral disease have traditionally relied on attenuated virus strains or inactivation of infectious virus. Subunit vaccines based on viral proteins expressed in heterologous systems have been effective for some pathogens, but have often suffered from poor immunogenicity due to incorrect protein folding or modification. In this chapter we focus on a specific class of viral subunit vaccine that mimics the overall structure of virus particles and thus preserves the native antigenic conformation of the immunogenic proteins. These virus-like particles (VLPs) have been produced for a wide range of taxonomically and structurally distinct viruses, and have unique advantages in terms of safety and immunogenicity over previous approaches. With new VLP vaccines for papillomavirus beginning to reach the market place we argue that this technology has now 'come-of-age' and must be considered a viable vaccine strategy.

Assessment of Tdap Vaccination Effectiveness in Adolescents in Integrated Health-Care Systems.

PubMed

Briere, Elizabeth C; Pondo, Tracy; Schmidt, Mark; Skoff, Tami; Shang, Nong; Naleway, Alison; Martin, Stacey; Jackson, Michael L

2018-06-01

Despite high national vaccination coverage with tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccines among U.S. adolescents, rates of adolescent pertussis disease are increasing. We estimated the duration of protection after Tdap vaccination and the possible effects of the change from whole-cell to acellular childhood pertussis vaccines in the United States during the 1990s. We conducted a retrospective cohort analysis among 11- to 18-year-olds enrolled in two integrated health-care delivery systems during 2005-2012. Cases met the Council of State and Territorial Epidemiologists' confirmed or probable definition or a polymerase chain reaction-positive suspect definition. We estimated vaccine effectiveness (VE) overall and by time since Tdap receipt. We stratified VE estimates by primary series pertussis vaccine received (based on birth year): mixed-vaccine cohort (1987-1997) and acellular vaccine cohort (1998-2001). The overall Tdap VE was 57% (95% confidence interval [CI]: 42%-68%); the VE in the mixed-vaccine and acellular cohorts was 65% (95% CI: 44%-78%) and 52% (95% CI: 30%-68%), respectively. Tdap VE within <2 years post vaccination (69%, 95% CI: 54%-79%) was significantly different from VE ≥2 years post vaccination (34%, 95% CI: 1%-55%, p value < .01). VE was significantly higher <2 years post vaccination compared with ≥2 years post vaccination in both mixed-vaccine (87%, 95% CI: 58%-96%, and 52%, 95% CI: 13%-73%; p value = .04) and acellular cohorts (62%, 95% CI: 41%-76%, and 21%, 95% CI: -30% to 52%; p value = .01). Although Tdap vaccination remains the best pertussis prevention method for adolescents, protection wanes within 2 years regardless of the type of childhood primary vaccine. Vaccines with longer duration of protection could decrease pertussis burden. Copyright © 2018 The Society for Adolescent Health and Medicine. All rights reserved.

Hypertension Vaccine may be a boon to millions in developing world.

PubMed

Bairwa, Mohan; Pilania, Manju; Gupta, Vivek; Yadav, Kapil

2014-01-01

Hypertension affects around 40% adults aged 25 years and more worldwide, and accounts for 7% of total disability-adjusted life-years. A simple algorithmic program is required to manage hypertension consisting of screening, life style measures, treatment and follow-up, a reliable drug supply and distribution system, and a credible health information system. Despite availability of effective antihypertensive drugs, long term treatment is still costly, tedious, and at the population level rather unsuccessful. Hypertension leaves patients and families with an avoidable heavy economic burden due to failure to control blood pressure. Health policy needs to address gross imbalance between prevention and management by increasing contribution to the preventive programs. During 21st century, the risk factors for morbidity and mortality have been changed, and researchers have started to work upon vaccines against lifestyle diseases like hypertension, diabetes etc. Researchers began experimenting with vaccines against the renin-angiotensin system to control hypertension around six decades ago. The vaccine candidates against hypertension namely ATR12181, pHAV-4Ang IIs, CYT006-AngQb, AngI-R, ATRQβ-001 have shown promising results. A candidate vaccine, CYT006-AngQb, has crossed initial phase and moved into phase 2 trials. However, more human studies in subsequent phases of trials are required to establish the safety and efficacy of anti-hypertensive vaccine. If proved safe and cost effective, a vaccine even with 50% efficacy against hypertension may protect about 90 million people from hypertension and its heavy economic burden. It can be an appropriate solution for low compliance to antihypertensive drug therapy as well as an avalanche to induce efforts on various chronic disease vaccine development programs.

Varicella (Chickenpox) Vaccine

MedlinePlus

ProQuad® (as a combination product containing Measles Vaccine, Mumps Vaccine, Rubella Vaccine, Varicella Vaccine) ... Has a parent, brother, or sister with a history of immune system problems. Is taking salicylates (such ...

Reports to the Vaccine Adverse Event Reporting System after hepatitis A and hepatitis AB vaccines in pregnant women.

PubMed

Moro, Pedro L; Museru, Oidda I; Niu, Manette; Lewis, Paige; Broder, Karen

2014-06-01

To characterize adverse events (AEs) after hepatitis A vaccines (Hep A) and hepatitis A and hepatitis B combination vaccine (Hep AB) in pregnant women reported to the Vaccine Adverse Event Reporting System (VAERS), a spontaneous reporting surveillance system. We searched VAERS for AEs reports in pregnant women who received Hep A or Hep AB from Jan. 1, 1996-April 5, 2013. Clinicians reviewed all reports and available medical records. VAERS received 139 reports of AEs in pregnant women; 7 (5.0%) were serious; no maternal or infant deaths were identified. Sixty-five (46.8%) did not describe any AEs. For those women whose gestational age was available, most were vaccinated during the first trimester, 50/60 (83.3%) for Hep A and 18/21 (85.7%) for Hep AB. The most common pregnancy-specific outcomes following Hep A or Hep AB vaccinations were spontaneous abortion in 15 (10.8%) reports, elective termination in 10 (7.2%), and preterm delivery in 7 (5.0%) reports. The most common nonpregnancy specific outcome was urinary tract infection and nausea/vomiting with 3 (2.2%) reports each. One case of amelia of the lower extremities was reported in an infant following maternal Hep A immunization. This review of VAERS reports did not identify any concerning pattern of AEs in pregnant women or their infants following maternal Hep A or Hep AB immunizations during pregnancy. Published by Mosby, Inc.

Estimated costs associated with improving influenza vaccination for health care personnel in a multihospital health system.

PubMed

Lin, Chyongchiou Jeng; Nowalk, Mary Patricia; Zimmerman, Richard K

2012-02-01

Health care personnel (HCP) are an important target group for influenza vaccination because of their close contact with vulnerable patients. Annual influenza vaccination for HCP is recommended to reduce the spread of influenza and decrease staff illness and absenteeism. UPMC Health System, the largest health system in western Pennsylvania, established a quality improvement project to increase influenza vaccination among its > 50,000 employees by implementing survey-informed interventions. At the completion of the intervention, estimates were prepared of the costs associated with implementing a multifaceted quality improvement intervention to improve HCP influenza vaccination rates in a large multihospital health system. All 11 participating hospitals provided education and publicity regarding influenza vaccination and provided vaccine free of charge at mass vaccination clinics. Two additional strategies-mobile vaccination carts and incentives-were implemented in a factorial design such that the hospitals had either carts, incentives, both strategies, or neither. The minimum and maximum costs per vaccinated employee by type of intervention were estimated using cost data for vaccine/supplies, labor, incentives, and administration. The average costs per vaccinated employee ranged from $24.55 to $30.43 for incentives and carts, $20.66 to $25.57 for incentives, $23.24 to $26.54 for carts, and $18.03 to $20.60 for education and publicity only. Vaccination rates increased significantly but remained below ideal levels. Influenza vaccination rates among nonphysician HCP can be improved using various interventions at a low cost per vaccinated employee. The costs for these nonmandatory interventions were modest compared with the costs typically associated with influenza-related absenteeism.

Understanding the immune response to seasonal influenza vaccination in older adults: a systems biology approach.

PubMed

Lambert, Nathaniel D; Ovsyannikova, Inna G; Pankratz, V Shane; Jacobson, Robert M; Poland, Gregory A

2012-08-01

Annual vaccination against seasonal influenza is recommended to decrease disease-related mortality and morbidity. However, one population that responds suboptimally to influenza vaccine is adults over the age of 65 years. The natural aging process is associated with a complex deterioration of multiple components of the host immune system. Research into this phenomenon, known as immunosenescence, has shown that aging alters both the innate and adaptive branches of the immune system. The intricate mechanisms involved in immune response to influenza vaccine, and how these responses are altered with age, have led us to adopt a more encompassing systems biology approach to understand exactly why the response to vaccination diminishes with age. Here, the authors review what changes occur with immunosenescence, and some immunogenetic factors that influence response, and outline the systems biology approach to understand the immune response to seasonal influenza vaccination in older adults.

Contraceptive vaccines for wildlife: a review.

PubMed

Kirkpatrick, Jay F; Lyda, Robin O; Frank, Kimberly M

2011-07-01

Wildlife, free-ranging and captive, poses and causes serious population problems not unlike those encountered with human overpopulation. Traditional lethal control programs, however, are not always legal, wise, safe, or publicly acceptable; thus, alternative approaches are necessary. Immunocontraception of free-ranging wildlife has reached the management level, with success across a large variety of species. Thus far, the immunocontraceptive research and management applications emphasis have been centered on porcine zona pellucida and gonadotropin-releasing hormone vaccines. Contraceptive success has been achieved in more than 85 different wildlife species, at the level of both the individual animal and the population. At the population management level with free-ranging species, the primary focus has been on wild horses, urban deer, bison, and African elephants. The challenges in the development and application of vaccine-based wildlife contraceptives are diverse and include differences in efficacy across species, safety of vaccines during pregnancy, the development of novel delivery systems for wild and wary free-ranging animals, and the constraints of certain non-contraceptive effects, such as effects on behavior. Beyond the constraints imposed by the public and a host of regulatory concerns, there exists a real limitation for funding of well-designed programs that apply this type of fertility control. © 2011 John Wiley & Sons A/S.

Human Papillomavirus Vaccine Coverage and Prevalence of Missed Opportunities for Vaccination in an Integrated Healthcare System.

PubMed

Irving, Stephanie A; Groom, Holly C; Stokley, Shannon; McNeil, Michael M; Gee, Julianne; Smith, Ning; Naleway, Allison L

2018-03-01

been influenced by ongoing health system best practices. HPV vaccine coverage rates varied significantly according to department, which could allow for targeted improvement opportunities. Copyright © 2017 Academic Pediatric Association. All rights reserved.

Avian influenza vaccines and vaccination in birds.

PubMed

Capua, Ilaria; Alexander, Dennis J

2008-09-12

Although the use of vaccines against avian influenza viruses in birds has been discouraged over the years, the unprecedented occurrence of outbreaks caused by avian influenza (AI) viruses in recent times has required review of this policy. A variety of products are now available on the market, ranging from inactivated conventional to live recombinant products. The general consensus on the use of vaccination is that if complying to GMP standards and properly administered, birds will be more resistant to field challenge and will exhibit reduced shedding levels in case of infection. However, viral circulation may still occur in a clinically healthy vaccinated population. This may result in an endemic situation and in the emergence of antigenic variants. In order to limit these risks, monitoring programmes enabling the detection of field exposure in vaccinated populations are recommended by international organisations and are essential to allow the continuation of international trade. Adequate management of a vaccination campaign, including monitoring, improved biosecurity and restriction is essential for the success of any control program for AI.

Motor palsies of cranial nerves (excluding VII) after vaccination: reports to the US Vaccine Adverse Event Reporting System.

PubMed

Woo, Emily Jane; Winiecki, Scott K; Ou, Alan C

2014-01-01

We reviewed cranial nerve palsies, other than VII, that have been reported to the US Vaccine Adverse Event Reporting System (VAERS). We examined patterns for differences in vaccine types, seriousness, age, and clinical characteristics. We identified 68 reports of cranial nerve palsies, most commonly involving the oculomotor (III), trochlear (IV), and abducens (VI) nerves. Isolated cranial nerve palsies, as well as palsies occurring as part of a broader clinical entity, were reported. Forty reports (59%) were classified as serious, suggesting that a cranial nerve palsy may sometimes be the harbinger of a broader and more ominous clinical entity, such as a stroke or encephalomyelitis. There was no conspicuous clustering of live vs. inactivated vaccines. The patient age range spanned the spectrum from infants to the elderly. Independent data may help to clarify whether, when, and to what extent the rates of cranial nerve palsies following particular vaccines may exceed background levels.

Association rule mining in the US Vaccine Adverse Event Reporting System (VAERS).

PubMed

Wei, Lai; Scott, John

2015-09-01

Spontaneous adverse event reporting systems are critical tools for monitoring the safety of licensed medical products. Commonly used signal detection algorithms identify disproportionate product-adverse event pairs and may not be sensitive to more complex potential signals. We sought to develop a computationally tractable multivariate data-mining approach to identify product-multiple adverse event associations. We describe an application of stepwise association rule mining (Step-ARM) to detect potential vaccine-symptom group associations in the US Vaccine Adverse Event Reporting System. Step-ARM identifies strong associations between one vaccine and one or more adverse events. To reduce the number of redundant association rules found by Step-ARM, we also propose a clustering method for the post-processing of association rules. In sample applications to a trivalent intradermal inactivated influenza virus vaccine and to measles, mumps, rubella, and varicella (MMRV) vaccine and in simulation studies, we find that Step-ARM can detect a variety of medically coherent potential vaccine-symptom group signals efficiently. In the MMRV example, Step-ARM appears to outperform univariate methods in detecting a known safety signal. Our approach is sensitive to potentially complex signals, which may be particularly important when monitoring novel medical countermeasure products such as pandemic influenza vaccines. The post-processing clustering algorithm improves the applicability of the approach as a screening method to identify patterns that may merit further investigation. Copyright © 2015 John Wiley & Sons, Ltd.

The data management of a phase III efficacy trial of an 11-valent pneumococcal conjugate vaccine and related satellite studies conducted in the Philippines

PubMed Central

2012-01-01

Background A large phase III placebo-controlled, randomized efficacy trial of an investigational 11-valent pneumococcal conjugate vaccine against pneumonia in children less than 2 years of age was conducted in the Philippines from July 2000 to December 2004. Clinical data from 12,194 children who were given either study vaccine or placebo was collected from birth up to two years of age for the occurrence of radiologically proven pneumonia as the primary endpoint, and for clinical pneumonia and invasive pneumococcal disease as the secondary endpoints. Several tertiary endpoints were also explored. Along the core trial, several satellite studies on herd immunity, cost-effectiveness of the study vaccine, acute otitis media, and wheezing were conducted. Results We describe here in detail how the relevant clinical records were managed and how quality control procedures were implemented to ensure that valid data were obtained respectively for the core trial and for the satellite studies. We discuss how the task was achieved, what the challenges were and what might have been done differently. Conclusions There were several factors that made the task of data management doable and efficient. First, a pre-trial data management system was available. Secondly, local committed statisticians, programmers and support staff were available and partly familiar to clinical trials. Thirdly, the personnel had undergone training during trial and grew with the task they were supposed to do. Thus the knowledge needed to develop and operate clinical data system was fully transferred to local staff. Trial registration Current Controlled Trials ISRCTN62323832 PMID:22676626

Mass psychogenic illness after vaccination.

PubMed

Clements, C John

2003-01-01

When vaccines are administered to groups, the physical reactions of the recipients may be similar, causing a form of mass reaction, the mechanism for which is the same as that for mass reactions from other causes. These phenomena have been categorised as mass psychogenic illness (MPI), and have been defined as the collective occurrence of a constellation of symptoms suggestive of organic illness but without an identified cause in a group of people with shared beliefs about the cause of the symptom(s). A review of the literature shows that such outbreaks have been reported in differing cultural and environmental settings including developing and industrialised countries, in the work place, on public transport, in schools, and the military. The perceived threats have been against agents such as food poisoning, fire and toxic gases. Whatever the place or perceived threat, the response seems to be similar. The symptoms generally included headache, dizziness, weakness, and loss of consciousness. Once under way, MPIs are not easy to stop. Incidents reported in the literature show that they can quickly gather momentum and can be amplified by the press who disseminate information rapidly, escalating the events. Management of such mass events can be extremely difficult. Should the public health official in charge continue to try and determine the cause, or should this person call off the entire investigation? It is suggested here that once vaccines are identified as a probable cause of the phenomenon, a dismissive approach may actually be harmful. Unless the spokesperson has already earned a high level of trust, the public are not likely to be convinced easily that nothing was wrong with the vaccine until it has been tested. An increased awareness of MPIs on the part of organisers of future mass vaccination campaigns seems appropriate. Immunisation managers should be aware that mass immunisation campaigns could generate such mass reactions. It is therefore essential that

Polio Endgame: Lessons Learned From the Immunization Systems Management Group.

PubMed

Zipursky, Simona; Vandelaer, Jos; Brooks, Alan; Dietz, Vance; Kachra, Tasleem; Farrell, Margaret; Ottosen, Ann; Sever, John L; Zaffran, Michel J

2017-07-01

The Immunization Systems Management Group (IMG) was established to coordinate and oversee objective 2 of the Polio Eradication and Endgame Strategic Plan 2013-2018, namely, (1) introduction of ≥1 dose of inactivated poliovirus vaccine in all 126 countries using oral poliovirus vaccine (OPV) only as of 2012, (2) full withdrawal of OPV, starting with the withdrawal of its type 2 component, and (3) using polio assets to strengthen immunization systems in 10 priority countries. The IMG's inclusive, transparent, and partnership-focused approach proved an effective means of leveraging the comparative and complementary strengths of each IMG member agency. This article outlines 10 key factors behind the IMG's success, providing a potential set of guiding principles for the establishment and implementation of other interagency collaborations and initiatives beyond the polio sphere. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

New South Wales annual vaccine-preventable disease report, 2013.

PubMed

Rosewell, Alexander; Spokes, Paula; Gilmour, Robin

2015-01-01

To describe the epidemiology of selected vaccine-preventable diseases in New South Wales, Australia for 2013. Data from the New South Wales Notifiable Conditions Information Management System were analysed by local health district of residence, age, Aboriginality, vaccination status and organism. Risk factor and vaccination status data were collected by public health units. Pertussis notification rates in infants were low, and no infant pertussis deaths were reported. Despite a high number of imported measles cases, there was limited secondary transmission. The invasive meningococcal disease notification rate declined, and disease due to serogroup C remained low and stable. Vaccine-preventable diseases were relatively well controlled in New South Wales in 2013, with declining or stable notification rates in most diseases compared with the previous year.

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

PubMed

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

2012-06-08

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

Synergizing vaccinations with therapeutics for measles eradication.

PubMed

Plemper, Richard K; Hammond, Anthea L

2014-02-01

The measles virus is a major human pathogen responsible for approximately 150,000 deaths annually. The disease is vaccine preventable and eradication of the virus is considered feasible, in principle. However, a herd immunity exceeding 95% is required to prevent sporadic viral outbreaks in a population. Declining disease prevalence, combined with public anxiety over the vaccination's safety, has led to increased vaccine refusal, especially in Europe. This has led to the resurgence of measles in some areas. This article discusses whether synergizing effective measles therapeutics with the measles vaccination could contribute to finally eradicating measles. The authors identify key elements in a desirable drug profile and review current disease management strategies and the state of experimental inhibitor candidates. The authors also evaluate the risk associated with viral escape from inhibition, and consider the potential of measles therapeutics in the management of persistent central nervous system (CNS) viral infection. Finally, the authors contemplate the possible impact of therapeutics in controlling the threat imposed by closely related zoonotic pathogens of the same genus as measles. Efficacious therapeutics used for post-exposure prophylaxis of high-risk social contacts of confirmed index cases may aid measles eradication by closing herd immunity gaps; this is due to vaccine refusal or failure in populations with overall good vaccination coverage. The envisioned primarily prophylactic application of measles therapeutics to a predominantly pediatric and/or adolescent population, dictates the drug profile. It also has to be safe and efficacious, orally available, shelf-stable at ambient temperature and amenable to cost-effective manufacturing.

Communication about vaccinations in Italian websites

PubMed Central

Tafuri, Silvio; Gallone, Maria S; Gallone, Maria F; Zorico, Ivan; Aiello, Valeria; Germinario, Cinzia

2014-01-01

Babies’ parents and people who look for information about vaccination often visit anti-vaccine movement’s websites, blogs by naturopathic physicians or natural and alternative medicine practitioners. The aim of this work is to provide a quantitative analysis on the type of information available to Italian people regarding vaccination and a quality analysis of websites retrieved through our searches. A quality score was created to evaluate the technical level of websites. A research was performed through Yahoo, Google, and MSN using the keywords “vaccine” and “vaccination,” with the function “OR” in order to identify the most frequently used websites. The 2 keywords were input in Italian, and the first 15 pages retrieved by each search engine were analyzed. 149 websites were selected through this methodology. Fifty-three per cent of the websites belonged to associations, groups, or scientific companies, 32.2% (n = 48) consisted of a personal blog and 14.8% (n = 22) belonged to some of the National Health System offices. Among all analyzed websites, 15.4% (n = 23) came from anti-vaccine movement groups. 37.6% reported webmaster name, 67.8% webmaster e-mail, 28.6% indicated the date of the last update and 46.6% the author’s name. The quality score for government sites was higher on average than anti-vaccine websites; although, government sites don’t use Web 2.0 functions, as the forums. National Health System institutions who have to promote vaccination cannot avoid investing in web communication because it cannot be managed by private efforts but must be the result of Public Health, private and scientific association, and social movement synergy. PMID:24607988

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

PubMed

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

2016-09-22

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

Factors associated with delayed measles vaccination among children in Shenzhen, China: A case-control study

PubMed Central

Lin, Weiyan; Xiong, Yongzhen; Tang, Hao; Chen, Baoli; Ni, Jindong

2015-01-01

A delay in the first dose of measles-containing vaccine (MCV1) may contribute to outbreaks of measles, resulting in a high age-specific incidence in infants <1 y of age. To determine the factors associated with delayed MCV1 vaccinations, we used data from the China Information Management System for Immunization Programming. Additionally, the parents/guardians of 430 children whose MCV1 vaccinations were delayed, as well as the parents/guardians of 424 children who received timely vaccinations, were surveyed by telephone. Children were less likely to receive timely MCV1 vaccinations if they belonged to an immigrant group, were male, had poor health status, had a father whose occupation e.g., a manager, had a history of delays in other Expanded Programs on Immunization (EPI) vaccinations, had parents who did not believe vaccinations were important for their children, and experienced shorter travel times to and longer waiting times in EPI clinics. The children of mothers whose occupational status (technician) were more likely to receive timely MCV1 vaccinations. The timeliness of MCV1 vaccinations should be considered as an additional indicator of the quality of vaccination programs. PMID:25668667

Factors associated with delayed measles vaccination among children in Shenzhen, China: a case-control study.

PubMed

Lin, Weiyan; Xiong, Yongzhen; Tang, Hao; Chen, Baoli; Ni, Jindong

2014-01-01

A delay in the first dose of measles-containing vaccine (MCV1) may contribute to outbreaks of measles, resulting in a high age-specific incidence in infants<1 y of age. To determine the factors associated with delayed MCV1 vaccinations, we used data from the China Information Management System for Immunization Programming. Additionally, the parents/guardians of 430 children whose MCV1 vaccinations were delayed, as well as the parents/guardians of 424 children who received timely vaccinations, were surveyed by telephone. Children were less likely to receive timely MCV1 vaccinations if they belonged to an immigrant group, were male, had poor health status, had a father whose occupation e.g., a manager, had a history of delays in other Expanded Programs on Immunization (EPI) vaccinations, had parents who did not believe vaccinations were important for their children, and experienced shorter travel times to and longer waiting times in EPI clinics. The children of mothers whose occupational status (technician) were more likely to receive timely MCV1 vaccinations. The timeliness of MCV1 vaccinations should be considered as an additional indicator of the quality of vaccination programs.

The impact of new vaccine introduction on immunization and health systems: A review of the published literature

PubMed Central

Hyde, Terri B.; Dentz, Holly; Wang, Susan A.; Burchett, Helen E.; Mounier-Jack, Sandra; Mantel, Carsten F.

2015-01-01

We conducted a systematic review of the published literature to examine the impact of new vaccine introduction on countries’ immunization and broader health systems. Six publication databases were searched using 104 vaccine and health system-related search terms. The search yielded 15,795 unique articles dating from December 31, 1911 to September 29, 2010. Based on review of the title and abstract, 654 (4%) of these articles were found to be potentially relevant and were referred for full review. After full review, 130 articles were found to be relevant and included in the analysis. These articles represented vaccines introduced to protect against 10 different diseases (hepatitis A, hepatitis B, Haemophilus influenzae type b disease, human papilloma virus infection, influenza, Japanese encephalitis, meningococcal meningitis, Streptococcus pneumoniae disease, rotavirus diarrhea and typhoid), in various formulations and combinations. Most reviewed articles (97 [75%]) reported experiences in high-income countries. New vaccine introduction was most efficient when the vaccine was introduced into an existing delivery platform and when introduced in combination with a vaccine already in the routine childhood immunization schedule (i.e., as a combination vaccine). New vaccine introduction did not impact coverage of vaccines already included in the routine childhood immunization schedule. The need for increased cold chain capacity was frequently reported. New vaccines facilitated the introduction and widespread use of auto-disable syringes into the immunization and the broader health systems. The importance of training and education for health care workers and social mobilization was frequently noted. There was evidence in high-income countries that new vaccine introduction was associated with reduced health-care costs. Future evaluations of new vaccine introductions should include the systematic and objective assessment of the impacts on a country’s immunization system

Rheumatoid arthritis vaccine therapies: perspectives and lessons from therapeutic ligand epitope antigen presentation system vaccines for models of rheumatoid arthritis

PubMed Central

Rosenthal, Kenneth S.; Mikecz, Katalin; Steiner, Harold L.; Glant, Tibor T.; Finnegan, Alison; Carambula, Roy E.; Zimmerman, Daniel H.

2016-01-01

The current status of therapeutic vaccines for autoimmune diseases is reviewed with rheumatoid arthritis as the focus. Therapeutic vaccines for autoimmune diseases must regulate or subdue responses to common self-antigens. Ideally, such a vaccine would initiate an antigen-specific modulation of the T-cell immune response that drives the inflammatory disease. Appropriate animal models and types of T helper cells and signature cytokine responses that drive autoimmune disease are also discussed. Interpretation of these animal models must be done cautiously because the means of initiation, autoantigens, and even the signature cytokine and T helper cell (Th1 or Th17) responses that are involved in the disease may differ significantly from those in humans. We describe ligand epitope antigen presentation system vaccine modulation of T-cell autoimmune responses as a strategy for the design of therapeutic vaccines for rheumatoid arthritis, which may also be effective in other autoimmune conditions. PMID:25787143

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

PubMed

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

2017-08-12

Maternal and childhood vaccine decision-making begins prenatally. Amongst pregnant Australian women we aimed to ascertain vaccine information received, maternal immunisation uptake and attitudes and concerns regarding childhood vaccination. We also aimed to determine any correlation between a) intentions and concerns regarding childhood vaccination, (b) concerns about pregnancy vaccination, (c) socioeconomic status (SES) and (d) uptake of influenza and pertussis vaccines during pregnancy and routine vaccines during childhood. Women attending public antenatal clinics were recruited in three Australian states. Surveys were completed on iPads. Follow-up phone surveys were done three to six months post delivery, and infant vaccination status obtained via the Australian Childhood Immunisation Register (ACIR). Between October 2015 and March 2016, 975 (82%) of 1184 mothers consented and 406 (42%) agreed to a follow up survey, post delivery. First-time mothers (445; 49%) had significantly more vaccine concerns in pregnancy and only 73% had made a decision about childhood vaccination compared to 89% of mothers with existing children (p-value<0.001). 66% of mothers reported receiving enough information during pregnancy on childhood vaccination. In the post delivery survey, 46% and 82% of mothers reported receiving pregnancy influenza and pertussis vaccines respectively. The mother's degree of vaccine hesitancy and two attitudinal factors were correlated with vaccine uptake post delivery. There was no association between reported maternal vaccine uptake or SES and childhood vaccine uptake. First time mothers are more vaccine hesitant and undecided about childhood vaccination, and only two thirds of all mothers believed they received enough information during pregnancy. New interventions to improve both education and communication on childhood and maternal vaccines, delivered by midwives and obstetricians in the Australian public hospital system, may reduce vaccine hesitancy

Sensitization to gelatin in children with systemic non-immediate-type reactions to varicella vaccines.

PubMed

Sakaguchi, M; Miyazawa, H; Inouye, S

2000-03-01

We recently found that four children who experienced systemic immediate-type reactions to varicella vaccine with gelatin had anti-gelatin IgE. We also found systemic non-immediate-type allergic reactions, which mainly consist of systemic cutaneous signs, appearing several hours or more after the vaccination. To investigate the relationship between immune responses to gelatin and non-immediate-type reactions to gelatin-containing varicella vaccines, we measured anti-gelatin IgE and IgG in the sera of the children with these allergic reactions. Serum samples were taken from 21 children who showed non-immediate-type reactions to varicella vaccines. As a positive control, serum samples were taken from 33 children who showed immediate-type reactions to varicella vaccine and had anti-gelatin IgE. As a negative control, serum samples were taken from 50 children who showed no reaction to the vaccine. We then examined anti-gelatin IgE and IgG in sera of the children. Of 21 children with non-immediate-type reactions, two (10%) had anti-gelatin IgE and six (29%) had anti-gelatin IgG. In the positive control group, all 33 children with immediate-type reactions had anti-gelatin IgG as well as IgE. In the negative control group, all 50 children who showed no allergic reaction to varicella vaccines had neither anti-gelatin IgE nor IgG. These results suggest that the possibility exists that some non-immediate-type reactions to varicella vaccine are caused by immune reactions to gelatin.

Success and failure of vaccines against renin-angiotensin system components.

PubMed

Brown, Morris J

2009-10-01

Therapeutic vaccination pre-dated modern drugs as a possible strategy for treating hypertension. This approach is now being rediscovered, through use of modified angiotensins as immunogens together with carriers and adjuvants. Effective blockade of the renin-angiotensin system (RAS) with treatment twice a year might suit patients who dislike taking drugs on a daily basis and would also be an attractive option for those who have blood pressures in the prehypertensive range, if it can prevent hypertension itself from developing. Proof of concept with a vaccine whose efficacy is easy to measure will encourage development of further vaccines directed against targets such as aldosterone or other pathways where alternative treatments are scarce or absent. Two angiotensin-based vaccines are currently in development: PMD3117 comprises modified angiotensin I coupled to keyhole limpet hemocyanin, and Cyt006-AngQb is a conjugate of angiotensin II linked to virus particles. Early phase II studies in patients with hypertension demonstrated some efficacy, but the vaccines are not as effective as existing inhibitors of the RAS. Large studies now in progress will establish whether further modification of the immunogen or adjuvant is required to boost antibody titers.

A CRISPR/Cas9 and Cre/Lox system-based express vaccine development strategy against re-emerging Pseudorabies virus.

PubMed

Liang, Xun; Sun, Leqiang; Yu, Teng; Pan, Yongfei; Wang, Dongdong; Hu, Xueying; Fu, Zhenfang; He, Qigai; Cao, Gang

2016-01-18

Virus evolves rapidly to escape vaccine-induced immunity, posing a desperate demand for efficient vaccine development biotechnologies. Here we present an express vaccine development strategy based on CRISPR/Cas9 and Cre/Lox system against re-emerging Pseudorabies virus, which caused the recent devastating swine pseudorabies outbreak in China. By CRISPR/Cas9 system, the virulent genes of the newly isolated strain were simultaneously substituted by marker genes, which were subsequently excised using Cre/Lox system for vaccine safety concern. Notably, single cell FACS technology was applied to further promote virus purification efficiency. The combination of these state-of-art technologies greatly accelerated vaccine development. Finally, vaccination and challenge experiments proved this vaccine candidate's protective efficacy in pigs and the promise to control current pseudorabies outbreak. This is, to our knowledge, the first successful vaccine development based on gene edit technologies, demonstrating these technologies leap from laboratory to industry. It may pave the way for future express antiviral vaccine development.

A CRISPR/Cas9 and Cre/Lox system-based express vaccine development strategy against re-emerging Pseudorabies virus

PubMed Central

Liang, Xun; Sun, Leqiang; Yu, Teng; Pan, Yongfei; Wang, Dongdong; Hu, Xueying; Fu, Zhenfang; He, Qigai; Cao, Gang

2016-01-01

Virus evolves rapidly to escape vaccine-induced immunity, posing a desperate demand for efficient vaccine development biotechnologies. Here we present an express vaccine development strategy based on CRISPR/Cas9 and Cre/Lox system against re-emerging Pseudorabies virus, which caused the recent devastating swine pseudorabies outbreak in China. By CRISPR/Cas9 system, the virulent genes of the newly isolated strain were simultaneously substituted by marker genes, which were subsequently excised using Cre/Lox system for vaccine safety concern. Notably, single cell FACS technology was applied to further promote virus purification efficiency. The combination of these state-of-art technologies greatly accelerated vaccine development. Finally, vaccination and challenge experiments proved this vaccine candidate’s protective efficacy in pigs and the promise to control current pseudorabies outbreak. This is, to our knowledge, the first successful vaccine development based on gene edit technologies, demonstrating these technologies leap from laboratory to industry. It may pave the way for future express antiviral vaccine development. PMID:26777545

Non-conventional expression systems for the production of vaccine proteins and immunotherapeutic molecules

PubMed Central

Legastelois, Isabelle; Buffin, Sophie; Peubez, Isabelle; Mignon, Charlotte; Sodoyer, Régis; Werle, Bettina

2017-01-01

ABSTRACT The increasing demand for recombinant vaccine antigens or immunotherapeutic molecules calls into question the universality of current protein expression systems. Vaccine production can require relatively low amounts of expressed materials, but represents an extremely diverse category consisting of different target antigens with marked structural differences. In contrast, monoclonal antibodies, by definition share key molecular characteristics and require a production system capable of very large outputs, which drives the quest for highly efficient and cost-effective systems. In discussing expression systems, the primary assumption is that a universal production platform for vaccines and immunotherapeutics will unlikely exist. This review provides an overview of the evolution of traditional expression systems, including mammalian cells, yeast and E.coli, but also alternative systems such as other bacteria than E. coli, transgenic animals, insect cells, plants and microalgae, Tetrahymena thermophila, Leishmania tarentolae, filamentous fungi, cell free systems, and the incorporation of non-natural amino acids. PMID:27905833

Framework for Optimal Global Vaccine Stockpile Design for Vaccine-Preventable Diseases: Application to Measles and Cholera Vaccines as Contrasting Examples.

PubMed

Thompson, Kimberly M; Duintjer Tebbens, Radboud J

2016-07-01

Managing the dynamics of vaccine supply and demand represents a significant challenge with very high stakes. Insufficient vaccine supplies can necessitate rationing, lead to preventable adverse health outcomes, delay the achievements of elimination or eradication goals, and/or pose reputation risks for public health authorities and/or manufacturers. This article explores the dynamics of global vaccine supply and demand to consider the opportunities to develop and maintain optimal global vaccine stockpiles for universal vaccines, characterized by large global demand (for which we use measles vaccines as an example), and nonuniversal (including new and niche) vaccines (for which we use oral cholera vaccine as an example). We contrast our approach with other vaccine stockpile optimization frameworks previously developed for the United States pediatric vaccine stockpile to address disruptions in supply and global emergency response vaccine stockpiles to provide on-demand vaccines for use in outbreaks. For measles vaccine, we explore the complexity that arises due to different formulations and presentations of vaccines, consideration of rubella, and the context of regional elimination goals. We conclude that global health policy leaders and stakeholders should procure and maintain appropriate global vaccine rotating stocks for measles and rubella vaccine now to support current regional elimination goals, and should probably also do so for other vaccines to help prevent and control endemic or epidemic diseases. This work suggests the need to better model global vaccine supplies to improve efficiency in the vaccine supply chain, ensure adequate supplies to support elimination and eradication initiatives, and support progress toward the goals of the Global Vaccine Action Plan. © 2014 Society for Risk Analysis.

Nanogel antigenic protein-delivery system for adjuvant-free intranasal vaccines

NASA Astrophysics Data System (ADS)

Nochi, Tomonori; Yuki, Yoshikazu; Takahashi, Haruko; Sawada, Shin-Ichi; Mejima, Mio; Kohda, Tomoko; Harada, Norihiro; Kong, Il Gyu; Sato, Ayuko; Kataoka, Nobuhiro; Tokuhara, Daisuke; Kurokawa, Shiho; Takahashi, Yuko; Tsukada, Hideo; Kozaki, Shunji; Akiyoshi, Kazunari; Kiyono, Hiroshi

2010-07-01

Nanotechnology is an innovative method of freely controlling nanometre-sized materials. Recent outbreaks of mucosal infectious diseases have increased the demands for development of mucosal vaccines because they induce both systemic and mucosal antigen-specific immune responses. Here we developed an intranasal vaccine-delivery system with a nanometre-sized hydrogel (`nanogel') consisting of a cationic type of cholesteryl-group-bearing pullulan (cCHP). A non-toxic subunit fragment of Clostridium botulinum type-A neurotoxin BoHc/A administered intranasally with cCHP nanogel (cCHP-BoHc/A) continuously adhered to the nasal epithelium and was effectively taken up by mucosal dendritic cells after its release from the cCHP nanogel. Vigorous botulinum-neurotoxin-A-neutralizing serum IgG and secretory IgA antibody responses were induced without co-administration of mucosal adjuvant. Importantly, intranasally administered cCHP-BoHc/A did not accumulate in the olfactory bulbs or brain. Moreover, intranasally immunized tetanus toxoid with cCHP nanogel induced strong tetanus-toxoid-specific systemic and mucosal immune responses. These results indicate that cCHP nanogel can be used as a universal protein-based antigen-delivery vehicle for adjuvant-free intranasal vaccination.

Developmental Regression and Autism Reported to the Vaccine Adverse Event Reporting System

ERIC Educational Resources Information Center

Woo, Emily Jane; Ball, Robert; Landa, Rebecca; Zimmerman, Andrew W.; Braun, M. Miles

2007-01-01

We report demographic and clinical characteristics of children reported to the US Vaccine Adverse Event Reporting System (VAERS) as having autism or another developmental disorder after vaccination. We completed 124 interviews with parents and reviewed medical records for 31 children whose records contained sufficient information to evaluate the…

Development of oral CTL vaccine using a CTP-integrated Sabin 1 poliovirus-based vector system.

PubMed

Han, Seung-Soo; Lee, Jinjoo; Jung, Yideul; Kang, Myeong-Ho; Hong, Jung-Hyub; Cha, Min-Suk; Park, Yu-Jin; Lee, Ezra; Yoon, Cheol-Hee; Bae, Yong-Soo

2015-09-11

We developed a CTL vaccine vector by modification of the RPS-Vax system, a mucosal vaccine vector derived from a poliovirus Sabin 1 strain, and generated an oral CTL vaccine against HIV-1. A DNA fragment encoding a cytoplasmic transduction peptide (CTP) was integrated into the RPS-Vax system to generate RPS-CTP, a CTL vaccine vector. An HIV-1 p24 cDNA fragment was introduced into the RPS-CTP vector system and a recombinant poliovirus (rec-PV) named vRPS-CTP/p24 was produced. vRPS-CTP/p24 was genetically stable and efficiently induced Th1 immunity and p24-specific CTLs in immunized poliovirus receptor-transgenic (PVR-Tg) mice. In challenge experiments, PVR-Tg mice that were pre-immunized orally with vRPS-CTP/p24 were resistant to challenge with a lethal dose of p24-expressing recombinant vaccinia virus (rMVA-p24). These results suggested that the RPS-CTP vector system had potential for developing oral CTL vaccines against infectious diseases. Copyright © 2015 Elsevier Ltd. All rights reserved.

The search for a promising cell factory system for production of edible vaccine

PubMed Central

Barzegari, Abolfazl; Saeedi, Nazli; Zarredar, Habib; Barar, Jaleh; Omidi, Yadollah

2014-01-01

Despite worldwide vaccination against devastating diseases for decades, millions of children in remote and impoverished regions of the globe die every year from vaccine-preventable infectious diseases. The reasons for incomplete coverage of vaccination programs are based in part on the relatively high costs of conventional vaccinations, including mass production, refrigeration, transportation, and training as well as funding personnel for their administration. Plant-based edible vaccines (PEVs) have been introduced as a revolutionary cost-effective vaccination modality. However, they suffer from major deficiencies that have restricted their application to bench-scale. This article discusses the deficiencies of PEVs and also provides concise overview on the health-promoting, biological and biotechnological features of spirulina (Arthrospira). In short, we envision that spirulina could be considered as a potential alternative biofactory system to the plants toward the production of edible vaccines in high-yield with low-costs that other hosts cannot yet offer. PMID:25424962

Current evidence on intradermal influenza vaccines administered by Soluvia™ licensed micro injection system

PubMed Central

Icardi, Giancarlo; Orsi, Andrea; Ceravolo, Antonella; Ansaldi, Filippo

2012-01-01

Among the several strategies explored for (1) the enhancement of the immune response to influenza immunization, (2) the improvement of the vaccine acceptability and (3) the overcoming of the egg-dependency for vaccine production, intradermal administration of influenza vaccine emerges as a promising alternative to conventional intramuscular route, thanks to the recent availability of new delivery devices and the perception of advantages in terms of immunogenicity, safety, reduction of antigen content and acceptability.   Data from clinical trials performed in children, adults <60 y and elderly people and post-marketing surveillance demonstrate that actually, licensed intradermal influenza vaccines, Intanza™ 9 and 15 µg and Fluzone™ Intradermal, administered by the microinjection system Soluvia™, show an excellent acceptability, tolerability and safety profile. Formulations containing 9 and 15 μg per strain demonstrate, respectively, comparable and superior immunogenicity than conventional intramuscular vaccines. Licensed intradermal influenza vaccines can be considered a valid alternative to standard intramuscular vaccination offering significant advantages in low-responder populations and helping to increase influenza vaccination coverage rates especially in people with fear of needles or high apprehension associated with annual vaccination. PMID:22293531

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

PubMed Central

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

2017-01-01

Introduction Populations and routine childhood vaccine regimens have changed substantially since supply chains were designed in the 1980s, and introducing new vaccines during the “Decade of Vaccine” may exacerbate existing bottlenecks, further inhibiting the flow of all vaccines. Methods Working with the Mozambique Ministry of Health, our team implemented a new process that integrated HERMES computational simulation modeling and on-the-ground implementers to evaluate and improve the Mozambique vaccine supply chain using a system-re-design that integrated new supply chain structures, information technology, equipment, personnel, and policies. Results The alternative system design raised vaccine availability (from 66% to 93% in Gaza; from 76% to 84% in Cabo Delgado) and reduced the logistics cost per dose administered (from $0.53 to $0.32 in Gaza; from $0.38 to $0.24 in Cabo Delgado) as compared to the multi-tiered system under the current EPI. The alternative system also produced higher availability at lower costs after new vaccine introductions. Since reviewing scenarios modeling deliveries every two months in the north of Gaza, the provincial directorate has decided to pilot this approach diverging from decades of policies dictating monthly deliveries. Discussion Re-design improved not only supply chain efficacy but also efficiency, important since resources to deliver vaccines are limited. The Mozambique experience and process can serve as a model for other countries during the Decade of Vaccines. For the Decade of Vaccines, getting vaccines at affordable prices to the market is not enough. Vaccines must reach the population to be successful. PMID:27576077

Genome-derived vaccines.

PubMed

De Groot, Anne S; Rappuoli, Rino

2004-02-01

Vaccine research entered a new era when the complete genome of a pathogenic bacterium was published in 1995. Since then, more than 97 bacterial pathogens have been sequenced and at least 110 additional projects are now in progress. Genome sequencing has also dramatically accelerated: high-throughput facilities can draft the sequence of an entire microbe (two to four megabases) in 1 to 2 days. Vaccine developers are using microarrays, immunoinformatics, proteomics and high-throughput immunology assays to reduce the truly unmanageable volume of information available in genome databases to a manageable size. Vaccines composed by novel antigens discovered from genome mining are already in clinical trials. Within 5 years we can expect to see a novel class of vaccines composed by genome-predicted, assembled and engineered T- and Bcell epitopes. This article addresses the convergence of three forces--microbial genome sequencing, computational immunology and new vaccine technologies--that are shifting genome mining for vaccines onto the forefront of immunology research.

New South Wales annual vaccine-preventable disease report, 2013

PubMed Central

Rosewell, Alexander; Spokes, Paula

2015-01-01

Aim To describe the epidemiology of selected vaccine-preventable diseases in New South Wales, Australia for 2013. Methods Data from the New South Wales Notifiable Conditions Information Management System were analysed by local health district of residence, age, Aboriginality, vaccination status and organism. Risk factor and vaccination status data were collected by public health units. Results Pertussis notification rates in infants were low, and no infant pertussis deaths were reported. Despite a high number of imported measles cases, there was limited secondary transmission. The invasive meningococcal disease notification rate declined, and disease due to serogroup C remained low and stable. Conclusion Vaccine-preventable diseases were relatively well controlled in New South Wales in 2013, with declining or stable notification rates in most diseases compared with the previous year. PMID:26306215

Impact of routine rotavirus vaccination on all-cause and rotavirus hospitalizations during the first four years following vaccine introduction in Rwanda.

PubMed

Sibomana, Hassan; Rugambwa, Celse; Mwenda, Jason M; Sayinzoga, Felix; Iraguha, Gisele; Uwimana, Jeanine; Parashar, Umesh D; Tate, Jacqueline E

2018-05-10

Rwanda introduced pentavalent rotavirus vaccine into its national immunization program in 2012. To determine the long-term impact of rotavirus vaccine on disease burden in a high burden setting, we examined trends in rotavirus and all-cause diarrhea hospitalizations in the first four years following rotavirus vaccine introduction. We used data from an active surveillance system, from a review of pediatric ward registries, and from the Health Management Information System to describe trends in rotavirus and all-cause diarrhea hospitalizations from January 2009 through December 2016. Percent reductions were calculated to compare the number of all-cause and rotavirus diarrhea hospitalizations pre- and post-rotavirus vaccine introduction. The proportion of diarrhea hospitalizations due to rotavirus declined by 25-44% among all children <5 years of age during 2013-2015 with a shift in rotavirus hospitalizations to older age groups. The proportion of total hospitalizations due to diarrhea among children <5 years of age decreased from 19% pre-vaccine introduction to 12-13% post-vaccine introduction. In the national hospital discharge data, substantial decreases were observed in all-cause diarrhea hospitalizations among children <5 years of age in 2013 and 2014 but these gains lessened in 2015-2016. Continued monitoring of long-term trends in all-cause diarrhea and rotavirus hospitalizations is important to ensure that the impact of the vaccination program is sustained over time and to better understand the changing age dynamics of diarrhea and rotavirus hospitalizations in the post-vaccine introduction era. Published by Elsevier Ltd.

Autoantibody response to adjuvant and nonadjuvant H1N1 vaccination in systemic lupus erythematosus.

PubMed

Urowitz, Murray B; Anton, Anoja; Ibanez, Dominique; Gladman, Dafna D

2011-11-01

It has been reported that influenza vaccination increases autoantibody production and/or disease activity in a significant proportion of patients with systemic lupus erythematosus (SLE). During the recent H1N1 epidemic, we investigated whether the use of adjuvant- and nonadjuvant-containing H1N1 vaccine induced increased autoantibody production in patients with SLE. Patients with SLE who received H1N1 vaccination and had a battery of 9 autoantibodies tested before and 1 and 3 months after vaccination were included. Antibodies tested included rheumatoid factor (nephelometry), antinuclear antibody (immunofluorescence), anti-DNA (Farr), anti-RNP, anti-Sm, anti-Ro, anti-La, anti-Scl-70, and anti-Jo-1 (enzyme-linked immunosorbent assay). Patients were evaluated by standard protocol, including items necessary to calculate the Systemic Lupus Erythematosus Disease Activity Index 2000 and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index. Descriptive statistics and McNemar's test were performed to evaluate change in antibody positivity. Multivariate logistic regression was performed to adjust for repeated measures in the comparisons of autoantibodies over visits and vaccine types. One hundred three patients (94 women, 9 men) with a mean ± SD age at vaccination of 43.9 ± 15.2 years and a mean ± SD disease duration of 14.2 ± 11.0 years were included. Fifty-one patients received adjuvant and 52 received nonadjuvant vaccines. Antibody testing was performed a mean of 1.9 months prior to the vaccination. The first postvaccination sample was taken a mean of 1 month after vaccination and the second a mean of 3.5 months after vaccination. The percentage of patients with changes in antibodies following vaccination was not statistically significant for most antibodies. After adjusting for the number of tests performed, none of the associations was significant. H1N1 vaccination (both adjuvant and nonadjuvant) did not increase the

Human papillomavirus vaccine uptake among individuals with systemic inflammatory diseases.

PubMed

Feldman, Candace H; Hiraki, Linda T; Lii, Huichuan; Seeger, John D; Kim, Seoyoung C

2015-01-01

The human papillomavirus (HPV) vaccine is safe and efficacious in patients with systemic inflammatory diseases (SID) who have higher rates of persistent HPV infection. We compared HPV vaccine uptake among SID and non-SID patients. Using a U.S. insurance claims database (2006-2012), we identified individuals 9-26 years with ≥2 SID diagnosis codes ≥7 days apart with ≥12 months of continuous enrollment prior to the second code (index date). We matched SID patients by age, sex and index date to randomly selected non-SID subjects and selected those with ≥24 months of post-index date continuous follow-up. We also identified a non-SID subcohort with ≥1 diagnosis code for asthma. We defined initiation as ≥1 HPV vaccination claim after 2007, and completion as 3 claims. We used multivariable logistic regression to assess uptake in females 11-26 years comparing SID, non-SID and asthma cohorts, adjusting for demographics, region, comorbidities, and healthcare utilization. We identified 5,642 patients 9-26 years with SID and 20,643 without. The mean age was 18.1 years (SD 4.9). We identified 1,083 patients with asthma; the mean age was 17.2 (SD 5.1). Among females, 20.6% with SID, 23.1% without SID and 22.9% with asthma, received ≥1 HPV vaccine. In our adjusted models, the odds of receipt of ≥1 vaccine was 0.87 times lower in SID (95% CI 0.77-0.98) compared to non-SID and did not differ for 3 vaccines (OR 1.03, 95% CI 0.83-1.26). The odds of initiation and completion were not statistically different between SID and non-SID asthma cohorts. In this nationwide cohort, HPV vaccine uptake was extremely low. Despite the heightened risk of persistent HPV infection among those with SID, no increase in HPV vaccine uptake was observed. Public health efforts to promote HPV vaccination overall are needed, and may be particularly beneficial for those at higher risk.

A SOA-Based Solution to Monitor Vaccination Coverage Among HIV-Infected Patients in Liguria.

PubMed

Giannini, Barbara; Gazzarata, Roberta; Sticchi, Laura; Giacomini, Mauro

2016-01-01

Vaccination in HIV-infected patients constitutes an essential tool in the prevention of the most common infectious diseases. The Ligurian Vaccination in HIV Program is a proposed vaccination schedule specifically dedicated to this risk group. Selective strategies are proposed within this program, employing ICT (Information and Communication) tools to identify this susceptible target group, to monitor immunization coverage over time and to manage failures and defaulting. The proposal is to connect an immunization registry system to an existing regional platform that allows clinical data re-use among several medical structures, to completely manage the vaccination process. This architecture will adopt a Service Oriented Architecture (SOA) approach and standard HSSP (Health Services Specification Program) interfaces to support interoperability. According to the presented solution, vaccination administration information retrieved from the immunization registry will be structured according to the specifications within the immunization section of the HL7 (Health Level 7) CCD (Continuity of Care Document) document. Immunization coverage will be evaluated through the continuous monitoring of serology and antibody titers gathered from the hospital LIS (Laboratory Information System) structured into a HL7 Version 3 (v3) Clinical Document Architecture Release 2 (CDA R2).

An oral microjet vaccination system elicits antibody production in rabbits.

PubMed

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

2017-03-08

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

History of the restoration of adenovirus type 4 and type 7 vaccine, live oral (Adenovirus Vaccine) in the context of the Department of Defense acquisition system.

PubMed

Hoke, Charles H; Snyder, Clifford E

2013-03-15

Respiratory pathogens cause morbidity and mortality in US military basic trainees. Following the influenza pandemic of 1918, and stimulated by WWII, the need to protect military personnel against epidemic respiratory disease was evident. Over several decades, the US military elucidated etiologies of acute respiratory diseases and invented and deployed vaccines to prevent disease caused by influenza, meningococcus, and adenoviruses. In 1994, the Adenovirus Vaccine manufacturer stopped its production. By 1999, supplies were exhausted and adenovirus-associated disease, especially serotype 4-associated febrile respiratory illness, returned to basic training installations. Advisory bodies persuaded Department of Defense leaders to initiate restoration of Adenovirus Vaccine. In 2011, after 10 years of effort by government and contractor personnel and at a cost of about $100 million, the Adenovirus Vaccine was restored to use at all military basic training installations. Disease and adenovirus serotype 4 isolation rates have fallen dramatically since vaccinations resumed in October 2011 and remain very low. Mindful of the adage that "The more successful a vaccine is, the more quickly the need for it will be forgotten.", sustainment of the supply of the Adenovirus Vaccine may be a challenge, and careful management will be required for such sustainment. Copyright © 2012 Elsevier Ltd. All rights reserved.

[Vaccine hesitancy: discourse analysis of parents who have not fully or partially vaccinated their children].

PubMed

Cruz Piqueras, Maite; Rodríguez García de Cortazar, Ainhoa; Hortal Carmona, Joaquín; Padilla Bernáldez, Javier

2017-09-16

To analyse and understand vaccination hesitancy discourses, particularly those of people who have decided not to vaccinate their sons and daughters. Qualitative study of five individual interviews and two focus groups with people who chose not to vaccinate their children in the province of Granada (Spain). Mothers and fathers manifest a system of health beliefs different to the biomedical paradigm. From an ethical point of view, they justify their position based on the right to autonomy and responsibility for their decisions. Alleged specific reasons: they doubt administration of several vaccines simultaneously at an early age in a systematic way and without individualising each case; they fear adverse effects and do not understand the variations of the vaccination schedule. These vaccination hesitancy discourses respond to the individual vs collective conflict; parents defend their right to bring up their children without any interference from the state and focus their responsibility on the individual welfare of their sons and daughters, regardless of the consequences that their actions might have on the collective. In their management of risks, they consider those derived from vaccination more relevant than the individual or collective consequences of not doing so. The vaccines generating most doubts are the more controversial ones within the scientific world. Transparency in communication of adverse effects; authorities respect for other health/disease concepts; banishment of the term "anti-vaccines" from the media and scientific vocabulary, and developing spaces for dialogue are bridges to be built. Copyright © 2017 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.

Economic benefits of keeping vaccines at ambient temperature during mass vaccination: the case of meningitis A vaccine in Chad

PubMed Central

Zipursky, Simona; Tevi-Benissan, Carole; Djingarey, Mamoudou Harouna; Gbedonou, Placide; Youssouf, Brahim Oumar; Zaffran, Michel

2014-01-01

Abstract Objective To evaluate the potential economic benefits of keeping a meningitis A vaccine at or near ambient temperature for up to 4 days during a mass vaccination campaign. Methods During a 10-day mass vaccination campaign against meningitis A in three regions of Chad in 2011, the costs associated with storage and transport of the vaccine in a traditional cold chain system were evaluated. A mathematical model was used to estimate the savings that could have been achieved if the vaccine had been stored at or near ambient temperature – in a “controlled temperature” chain – at the peripheral levels of the supply chain system. Findings The cost of the cold chain and associated logistics used in the campaign in Chad was 0.24 United States dollars (US$) per person vaccinated. In the modelled scenario for a controlled temperature chain, however, these costs dropped by 50% and were estimated to be only US$ 0.12 per person vaccinated. Conclusion The implementation of a “controlled temperature” chain at the most peripheral levels of the supply chain system – assuming no associated loss of vaccine potency, efficacy or safety – could result in major economic benefits and allow vaccine coverage to be extended in low-resource settings. PMID:24623901

Meningococcal vaccine introduction in Mali through mass campaigns and its impact on the health system

PubMed Central

Mounier-Jack, Sandra; Burchett, Helen Elizabeth Denise; Griffiths, Ulla Kou; Konate, Mamadou; Diarra, Kassibo Sira

2014-01-01

Objective: To evaluate the impact of the meningococcal A (MenA) vaccine introduction in Mali through mass campaigns on the routine immunization program and the wider health system. Methods: We used a mixed-methods case-study design, combining semi-structured interviews with 31 key informants, a survey among 18 health facilities, and analysis of routine health facility data on number of routine vaccinations and antenatal consultations before, during, and after the MenA vaccine campaign in December 2010. Survey and interview data were collected at the national level and in 2 regions in July and August 2011, with additional interviews in January 2012. Findings: Many health system functions were not affected—either positively or negatively—by the MenA vaccine introduction. The majority of effects were felt on the immunization program. Benefits included strengthened communication and social mobilization, surveillance, and provider skills. Drawbacks included the interruption of routine vaccination services in the majority of health facilities surveyed (67%). The average daily number of children receiving routine vaccinations was 79% to 87% lower during the 10-day campaign period than during other periods of the month. Antenatal care consultations were also reduced during the campaign period by 10% to 15%. Key informants argued that, with an average of 14 campaigns per year, mass campaigns would have a substantial cumulative negative effect on routine health services. Many also argued that the MenA campaign missed potential opportunities for health systems strengthening because integration with other health services was lacking. Conclusion: The MenA vaccine introduction interrupted routine vaccination and other health services. When introducing a new vaccine through a campaign, coverage of routine health services should be monitored alongside campaign vaccine coverage to highlight where and how long services are disrupted and to mitigate risks to routine services

Increasing Coverage of Appropriate Vaccinations

PubMed Central

Jacob, Verughese; Chattopadhyay, Sajal K.; Hopkins, David P.; Morgan, Jennifer Murphy; Pitan, Adesola A.; Clymer, John

2016-01-01

Context Population-level coverage for immunization against many vaccine-preventable diseases remains below optimal rates in the U.S. The Community Preventive Services Task Force recently recommended several interventions to increase vaccination coverage based on systematic reviews of the evaluation literature. The present study provides the economic results from those reviews. Evidence acquisition A systematic review was conducted (search period, January 1980 through February 2012) to identify economic evaluations of 12 interventions recommended by the Task Force. Evidence was drawn from included studies; estimates were constructed for the population reach of each strategy, cost of implementation, and cost per additional vaccinated person because of the intervention. Analyses were conducted in 2014. Evidence synthesis Reminder systems, whether for clients or providers, were among the lowest-cost strategies to implement and the most cost effective in terms of additional people vaccinated. Strategies involving home visits and combination strategies in community settings were both costly and less cost effective. Strategies based in settings such as schools and managed care organizations that reached the target population achieved additional vaccinations in the middle range of cost effectiveness. Conclusions The interventions recommended by the Task Force differed in reach, cost, and cost effectiveness. This systematic review presents the economic information for 12 effective strategies to increase vaccination coverage that can guide implementers in their choice of interventions to fit their local needs, available resources, and budget. PMID:26847663

Enhancement of Antituberculosis Immunity in a Humanized Model System by a Novel Virus-Vectored Respiratory Mucosal Vaccine.

PubMed

Yao, Yushi; Lai, Rocky; Afkhami, Sam; Haddadi, Siamak; Zganiacz, Anna; Vahedi, Fatemeh; Ashkar, Ali A; Kaushic, Charu; Jeyanathan, Mangalakumari; Xing, Zhou

2017-07-01

The translation of preclinically promising novel tuberculosis vaccines to ultimate human applications has been challenged by the lack of animal models with an immune system equivalent to the human immune system in its genetic diversity and level of susceptibility to tuberculosis. We have developed a humanized mice (Hu-mice) tuberculosis model system to investigate the clinical relevance of a novel virus-vectored (VV) tuberculosis vaccine administered via respiratory mucosal or parenteral route. We find that VV vaccine activates T cells in Hu-mice as it does in human vaccinees. The respiratory mucosal route for delivery of VV vaccine in Hu-mice, but not the parenteral route, significantly reduces the humanlike lung tuberculosis outcomes in a human T-cell-dependent manner. Our results suggest that the Hu-mouse can be used to predict the protective efficacy of novel tuberculosis vaccines/strategies before they proceed to large, expensive human trials. This new vaccine testing system will facilitate the global pace of clinical tuberculosis vaccine development. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Decreased Management of Genital Warts in Young Women in Australian General Practice Post Introduction of National HPV Vaccination Program: Results from a Nationally Representative Cross-Sectional General Practice Study

PubMed Central

Harrison, Christopher; Britt, Helena; Garland, Suzanne; Conway, Lynne; Stein, Alicia; Pirotta, Marie; Fairley, Christopher

2014-01-01

Objectives Since the introduction of Australia's human papillomavirus vaccination program, the management rate of genital warts in sexual health clinics and private hospitals has decreased in women of vaccine-eligible age. However, most genital warts in Australia are managed in general practice. This study examines whether a similar decrease occurred in Australian general practice after the introduction of the program. Methods Analysis of a nationally representative cross-sectional database of Australian general practice activity (1,175,879 patient encounters with 11,780 general practitioners). Genital warts management rates were estimated for the periods before and after introduction of the program (Pre-program, July 2002-June 2006; Post-program, July 2008-June 2012). Control conditions included genital herpes and gardnerella/bacterial vaginosis in female patients and genital herpes and urethritis in male patients. Trends in management rates by year, pre-vaccine (July 2000-June 2007) and post-vaccine (July 2007-June 2012) were also calculated. Results Management rate of genital warts among women potentially covered by program (aged 15–27 years) decreased by 61% from 4.33 per 1,000 encounters in the Pre-program period to 1.67 in the Post-program period. Trend analysis of the post-vaccine period showed, among women of vaccine eligible age, a significant year-on-year reduction in the rate of genital warts management (p<0.0001) and a significant increase in the management rate of control conditions per year (p<0.0001). For all other age-sex groups there was no significant change in the management rate of genital warts between the Pre- and Post-program periods. Conclusion The large decrease in general practice management of genital warts in women of vaccine-eligible age highlights the success of the program in the wider community. PMID:25180698

Decreased management of genital warts in young women in Australian general practice post introduction of national HPV vaccination program: results from a nationally representative cross-sectional general practice study.

PubMed

Harrison, Christopher; Britt, Helena; Garland, Suzanne; Conway, Lynne; Stein, Alicia; Pirotta, Marie; Fairley, Christopher

2014-01-01

Since the introduction of Australia's human papillomavirus vaccination program, the management rate of genital warts in sexual health clinics and private hospitals has decreased in women of vaccine-eligible age. However, most genital warts in Australia are managed in general practice. This study examines whether a similar decrease occurred in Australian general practice after the introduction of the program. Analysis of a nationally representative cross-sectional database of Australian general practice activity (1,175,879 patient encounters with 11,780 general practitioners). Genital warts management rates were estimated for the periods before and after introduction of the program (Pre-program, July 2002-June 2006; Post-program, July 2008-June 2012). Control conditions included genital herpes and gardnerella/bacterial vaginosis in female patients and genital herpes and urethritis in male patients. Trends in management rates by year, pre-vaccine (July 2000-June 2007) and post-vaccine (July 2007-June 2012) were also calculated. Management rate of genital warts among women potentially covered by program (aged 15-27 years) decreased by 61% from 4.33 per 1,000 encounters in the Pre-program period to 1.67 in the Post-program period. Trend analysis of the post-vaccine period showed, among women of vaccine eligible age, a significant year-on-year reduction in the rate of genital warts management (p<0.0001) and a significant increase in the management rate of control conditions per year (p<0.0001). For all other age-sex groups there was no significant change in the management rate of genital warts between the Pre- and Post-program periods. The large decrease in general practice management of genital warts in women of vaccine-eligible age highlights the success of the program in the wider community.

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

PubMed

Belyakov, I M; Ahlers, J D

2011-01-01

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

Evaluation of scanning 2D barcoded vaccines to improve data accuracy of vaccines administered.

PubMed

Daily, Ashley; Kennedy, Erin D; Fierro, Leslie A; Reed, Jenica Huddleston; Greene, Michael; Williams, Warren W; Evanson, Heather V; Cox, Regina; Koeppl, Patrick; Gerlach, Ken

2016-11-11

Accurately recording vaccine lot number, expiration date, and product identifiers, in patient records is an important step in improving supply chain management and patient safety in the event of a recall. These data are being encoded on two-dimensional (2D) barcodes on most vaccine vials and syringes. Using electronic vaccine administration records, we evaluated the accuracy of lot number and expiration date entered using 2D barcode scanning compared to traditional manual or drop-down list entry methods. We analyzed 128,573 electronic records of vaccines administered at 32 facilities. We compared the accuracy of records entered using 2D barcode scanning with those entered using traditional methods using chi-square tests and multilevel logistic regression. When 2D barcodes were scanned, lot number data accuracy was 1.8 percentage points higher (94.3-96.1%, P<0.001) and expiration date data accuracy was 11 percentage points higher (84.8-95.8%, P<0.001) compared with traditional methods. In multivariate analysis, lot number was more likely to be accurate (aOR=1.75; 99% CI, 1.57-1.96) as was expiration date (aOR=2.39; 99% CI, 2.12-2.68). When controlling for scanning and other factors, manufacturer, month vaccine was administered, and vaccine type were associated with variation in accuracy for both lot number and expiration date. Two-dimensional barcode scanning shows promise for improving data accuracy of vaccine lot number and expiration date records. Adapting systems to further integrate with 2D barcoding could help increase adoption of 2D barcode scanning technology. Published by Elsevier Ltd.

Induction of PrPSc-specific systemic and mucosal immune responses in white-tailed deer with an oral vaccine for chronic wasting disease

PubMed Central

Scruten, Erin; Woodbury, Murray; Potter, Andrew; Griebel, Philip; Tikoo, Suresh K.; Napper, Scott

2017-01-01

ABSTRACT The ongoing epidemic of chronic wasting disease (CWD) within cervid populations indicates the need for novel approaches for disease management. A vaccine that either reduces susceptibility to infection or reduces shedding of prions by infected animals, or a combination of both, could be of benefit for disease control. The development of such a vaccine is challenged by the unique nature of prion diseases and the requirement for formulation and delivery in an oral format for application in wildlife settings. To address the unique nature of prions, our group targets epitopes, termed disease specific epitopes (DSEs), whose exposure for antibody binding depends on disease-associated misfolding of PrPC into PrPSc. Here, a DSE corresponding to the rigid loop (RL) region, which was immunogenic following parenteral vaccination, was translated into an oral vaccine. This vaccine consists of a replication-incompetent human adenovirus expressing a truncated rabies glycoprotein G recombinant fusion with the RL epitope (hAd5:tgG-RL). Oral immunization of white-tailed deer with hAd5:tgG-RL induced PrPSc-specific systemic and mucosal antibody responses with an encouraging safety profile in terms of no adverse health effects nor prolonged vector shedding. By building upon proven strategies of formulation for wildlife vaccines, these efforts generate a particular PrPSc-specific oral vaccine for CWD as well as providing a versatile platform, in terms of carrier protein and biological vector, for generation of other oral, peptide-based CWD vaccines. PMID:28968152

Costing analysis and anthropological assessment of the vaccine supply chain system redesign in the Comé District (Benin).

PubMed

Huang, Xiao Xian; Guillermet, Elise; Le Gargasson, Jean-Bernard; Alfa, Daleb Abdoulaye; Gbodja, Romule; Sossou, Adanmavokin Justin; Jaillard, Phillippe

2017-04-19

At the end of 2013, a pilot experiment was carried out in Comé health zone (HZ) in an attempt to optimize the vaccine supply chain. Four commune vaccine storage facilities were replaced by one central HZ facility. This study evaluated the incremental financial needs for the establishment of the new system; compared the economic cost of the supply chain in the Comé HZ before and after the system redesign; and analyzed the changes induced by the pilot project in immunization logistics management. The purposive sampling method was used to draw a sample from 37 health facilities in the zone for costing evaluation. Data on inputs and prices were collected retrospectively for 2013 and 2014. The analysis used an ingredient-based approach. In addition, 44 semi-structured interviews with health workers for anthropological analysis were completed in 2014. The incremental financial costs amounted to US$55,148, including US$50,605 for upfront capital investment and US$4543 for ongoing recurrent costs. Annual economic cost per dose administered (including all vaccines distributed through the Expanded Program on Immunization (EPI)) in the Comé HZ increased from US$0.09 before system redesign to US$0.15 after implementation, mainly due to a high initial investment and the operational cost of HZ mobile warehouse. Interviews with health workers suggested that the redesigned system was associated with improvements in motivation and professional awareness due to training, supportive supervision, and improved work conditions. The system redesign involved a considerable investment at HZ level. Benefits were found in the reduction of transportation costs to health posts (HP) and commune health center (CHC) levels, and the strengthening of health workers professional skills at all levels in Comé. The redesigned system contributed to a decrease in funding needs at HP and CHC levels. The benefits of the investment need to be examined after the introduction of new vaccines and after a

Next generation vaccines.

PubMed

Riedmann, Eva M

2011-07-01

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

Reference set for performance testing of pediatric vaccine safety signal detection methods and systems.

PubMed

Brauchli Pernus, Yolanda; Nan, Cassandra; Verstraeten, Thomas; Pedenko, Mariia; Osokogu, Osemeke U; Weibel, Daniel; Sturkenboom, Miriam; Bonhoeffer, Jan

2016-12-12

Safety signal detection in spontaneous reporting system databases and electronic healthcare records is key to detection of previously unknown adverse events following immunization. Various statistical methods for signal detection in these different datasources have been developed, however none are geared to the pediatric population and none specifically to vaccines. A reference set comprising pediatric vaccine-adverse event pairs is required for reliable performance testing of statistical methods within and across data sources. The study was conducted within the context of the Global Research in Paediatrics (GRiP) project, as part of the seventh framework programme (FP7) of the European Commission. Criteria for the selection of vaccines considered in the reference set were routine and global use in the pediatric population. Adverse events were primarily selected based on importance. Outcome based systematic literature searches were performed for all identified vaccine-adverse event pairs and complemented by expert committee reports, evidence based decision support systems (e.g. Micromedex), and summaries of product characteristics. Classification into positive (PC) and negative control (NC) pairs was performed by two independent reviewers according to a pre-defined algorithm and discussed for consensus in case of disagreement. We selected 13 vaccines and 14 adverse events to be included in the reference set. From a total of 182 vaccine-adverse event pairs, we classified 18 as PC, 113 as NC and 51 as unclassifiable. Most classifications (91) were based on literature review, 45 were based on expert committee reports, and for 46 vaccine-adverse event pairs, an underlying pathomechanism was not plausible classifying the association as NC. A reference set of vaccine-adverse event pairs was developed. We propose its use for comparing signal detection methods and systems in the pediatric population. Published by Elsevier Ltd.

[Public health service prescriptions of vaccines not included in systematic vaccination programs in Valencian community, Spain, during the period 2004-2009].

PubMed

Ruiz Palacio, Ana; Pastor Villalba, Eliseo; Martín Ivorra, Rosa; Alguacil Ramos, Ana María; Portero Alonso, Antonio; Lluch Rodrigo, José Antonio

2011-06-01

In the context of the policies of rational use of medicine, and in order to achieve an efficient management of the vaccinations programs, we expect to know the number of packings and cost of prescribed vaccines not included in the vaccination programs of Valencian Community and its departments during 2009 and to analyze its evolution since 2004, focusing on an analysis of Heptavalent pneumococcal conjugate vaccine in children under two years old. Retrospective descriptive study to analyze the prescriptions of vaccines in Valencian Community during 2009 and its evolution since 2004. vaccine availability, number of packings, group of beneficiary (actives/pensioners), department, and cost of prescriptions. Gestor de Prestación Farmacéutica (GAIA) and Sistema Información Poblacional (SIP). In 2009 prescribed vaccines on official national health system prescription forms that are not included in vaccination programs, supposed a cost of 683.445,71 € corresponding to 17.353 packings (87% of the total prescribed vaccines). Heptavalent pneumococcal conjugate vaccine generated 72% of the total cost of vaccines not included in the vaccination programs. The trend from 2004 to 2009 shows an increase in expenditure of 735.334 € (24,66%) in 2005 from which there takes place a marked and gradual decrease that reaches 1.562.650,67 € (-228.64%). The cost by departments of prescriptions per 1000 children under two years old of pneumococcal conjugate vaccine ranges between 17.377 and 324 €. The declining trend of prescriptions, mainly of pneumococcal conjugate vaccines, continues during 2009. A great interdepartmental variability is observed, nevertheless, in rates of prescription that should be corrected.

The mucosal immune system: From dentistry to vaccine development

PubMed Central

KIYONO, Hiroshi; AZEGAMI, Tatsuhiko

2015-01-01

The oral cavity is the beginning of the aero-digestive tract, which is covered by mucosal epithelium continuously under the threat of invasion of pathogens, it is thus protected by the mucosal immune system. In the early phase of our scientific efforts for the demonstration of mucosal immune system, dental science was one of major driving forces due to their foreseeability to use oral immunity for the control of oral diseases. The mucosal immune system is divided functionally into, but interconnected inductive and effector sites. Intestinal Peyer’s patches (PPs) are an inductive site containing antigen-sampling M cells and immunocompetent cells required to initiate antigen-specific immune responses. At effector sites, PP-originated antigen-specific IgA B cells become plasma cells to produce polymeric IgA and form secretory IgA by binding to poly-Ig receptor expressed on epithelial cells for protective immunity. The development of new-generation mucosal vaccines, including the rice-based oral vaccine MucoRice, on the basis of the coordinated mucosal immune system is a promising strategy for the control of mucosal infectious diseases. PMID:26460320

Association of strategic management with vaccination in the terms of globalization.

PubMed

Rabrenovic, Mihajlo; Cukanovic Karavidic, Marija; Stosic, Ivana

2018-04-01

Globalization is having an ever growing impact on the field of vaccine production and distribution in the world and domestically. In this article we examine the impact of taking a strategic approach to vaccination programmes by all the relevant actors: WHO, UNICEF, national immunization programmes, and vaccine manufacturers and distributors. The review of the relevant literature indicates that there are commonalities to the worldwide vaccination programmes. A comparative analysis of various vaccination strategies recommended by WHO and the immunization calendars of certain European countriesis made as well as an analysis of the Serbian vaccination programme. New and more expensive vaccines will continue to appear on the market in increasingly short periods of time.

The Case for Adolescent HIV Vaccination in South Africa

PubMed Central

Moodley, Nishila; Gray, Glenda; Bertram, Melanie

2016-01-01

Abstract Despite comprising 0.7% of the world population, South Africa is home to 18% of the global human immunodeficiency virus (HIV) prevalence. Unyielding HIV subepidemics among adolescents threaten national attempts to curtail the disease burden. Should an HIV vaccine become available, establishing its point of entry into the health system becomes a priority. This study assesses the impact of school-based HIV vaccination and explores how variations in vaccine characteristics affect cost-effectiveness. The cost per quality adjusted life year (QALY) gained associated with school-based adolescent HIV vaccination services was assessed using Markov modeling that simulated annual cycles based on national costing data. The estimation was based on a life expectancy of 70 years and employs the health care provider perspective. The simultaneous implementation of HIV vaccination services with current HIV management programs would be cost-effective, even at relatively higher vaccine cost. At base vaccine cost of US$ 12, the incremental cost effectiveness ratio (ICER) was US$ 43 per QALY gained, with improved ICER values yielded at lower vaccine costs. The ICER was sensitive to duration of vaccine mediated protection and variations in vaccine efficacy. Data from this work demonstrate that vaccines offering longer duration of protection and at lower cost would result in improved ICER values. School-based HIV vaccine services of adolescents, in addition to current HIV prevention and treatment health services delivered, would be cost-effective. PMID:26825890

Peptide/protein vaccine delivery system based on PLGA particles.

PubMed

Allahyari, Mojgan; Mohit, Elham

2016-03-03

Due to the excellent safety profile of poly (D,L-lactide-co-glycolide) (PLGA) particles in human, and their biodegradability, many studies have focused on the application of PLGA particles as a controlled-release vaccine delivery system. Antigenic proteins/peptides can be encapsulated into or adsorbed to the surface of PLGA particles. The gradual release of loaded antigens from PLGA particles is necessary for the induction of efficient immunity. Various factors can influence protein release rates from PLGA particles, which can be defined intrinsic features of the polymer, particle characteristics as well as protein and environmental related factors. The use of PLGA particles encapsulating antigens of different diseases such as hepatitis B, tuberculosis, chlamydia, malaria, leishmania, toxoplasma and allergy antigens will be described herein. The co-delivery of antigens and immunostimulants (IS) with PLGA particles can prevent the systemic adverse effects of immunopotentiators and activate both dendritic cells (DCs) and natural killer (NKs) cells, consequently enhancing the therapeutic efficacy of antigen-loaded PLGA particles. We will review co-delivery of different TLR ligands with antigens in various models, highlighting the specific strengths and weaknesses of the system. Strategies to enhance the immunotherapeutic effect of DC-based vaccine using PLGA particles can be designed to target DCs by functionalized PLGA particle encapsulating siRNAs of suppressive gene, and disease specific antigens. Finally, specific examples of cellular targeting where decorating the surface of PLGA particles target orally administrated vaccine to M-cells will be highlighted.

Peptide/protein vaccine delivery system based on PLGA particles

PubMed Central

Allahyari, Mojgan; Mohit, Elham

2016-01-01

abstract Due to the excellent safety profile of poly (D,L-lactide-co-glycolide) (PLGA) particles in human, and their biodegradability, many studies have focused on the application of PLGA particles as a controlled-release vaccine delivery system. Antigenic proteins/peptides can be encapsulated into or adsorbed to the surface of PLGA particles. The gradual release of loaded antigens from PLGA particles is necessary for the induction of efficient immunity. Various factors can influence protein release rates from PLGA particles, which can be defined intrinsic features of the polymer, particle characteristics as well as protein and environmental related factors. The use of PLGA particles encapsulating antigens of different diseases such as hepatitis B, tuberculosis, chlamydia, malaria, leishmania, toxoplasma and allergy antigens will be described herein. The co-delivery of antigens and immunostimulants (IS) with PLGA particles can prevent the systemic adverse effects of immunopotentiators and activate both dendritic cells (DCs) and natural killer (NKs) cells, consequently enhancing the therapeutic efficacy of antigen-loaded PLGA particles. We will review co-delivery of different TLR ligands with antigens in various models, highlighting the specific strengths and weaknesses of the system. Strategies to enhance the immunotherapeutic effect of DC-based vaccine using PLGA particles can be designed to target DCs by functionalized PLGA particle encapsulating siRNAs of suppressive gene, and disease specific antigens. Finally, specific examples of cellular targeting where decorating the surface of PLGA particles target orally administrated vaccine to M-cells will be highlighted. PMID:26513024

Comparative Systems Analyses Reveal Molecular Signatures of Clinically tested Vaccine Adjuvants

NASA Astrophysics Data System (ADS)

Olafsdottir, Thorunn A.; Lindqvist, Madelene; Nookaew, Intawat; Andersen, Peter; Maertzdorf, Jeroen; Persson, Josefine; Christensen, Dennis; Zhang, Yuan; Anderson, Jenna; Khoomrung, Sakda; Sen, Partho; Agger, Else Marie; Coler, Rhea; Carter, Darrick; Meinke, Andreas; Rappuoli, Rino; Kaufmann, Stefan H. E.; Reed, Steven G.; Harandi, Ali M.

2016-12-01

A better understanding of the mechanisms of action of human adjuvants could inform a rational development of next generation vaccines for human use. Here, we exploited a genome wide transcriptomics analysis combined with a systems biology approach to determine the molecular signatures induced by four clinically tested vaccine adjuvants, namely CAF01, IC31, GLA-SE and Alum in mice. We report signature molecules, pathways, gene modules and networks, which are shared by or otherwise exclusive to these clinical-grade adjuvants in whole blood and draining lymph nodes of mice. Intriguingly, co-expression analysis revealed blood gene modules highly enriched for molecules with documented roles in T follicular helper (TFH) and germinal center (GC) responses. We could show that all adjuvants enhanced, although with different magnitude and kinetics, TFH and GC B cell responses in draining lymph nodes. These results represent, to our knowledge, the first comparative systems analysis of clinically tested vaccine adjuvants that may provide new insights into the mechanisms of action of human adjuvants.

"Why won't they just vaccinate?" Horse owner risk perception and uptake of the Hendra virus vaccine.

PubMed

Manyweathers, J; Field, H; Longnecker, N; Agho, K; Smith, C; Taylor, M

2017-04-13

Hendra virus is a paramyxovirus that causes periodic serious disease and fatalities in horses and humans in Australia first identified in 1994. Pteropid bats (commonly known as flying-foxes) are the natural host of the virus, and the putative route of infection in horses is by ingestion or inhalation of material contaminated by flying-fox urine or other bodily fluids. Humans become infected after close contact with infected horses. Horse owners in Australia are encouraged to vaccinate their horses against Hendra virus to reduce the risk of Hendra virus infection, and to prevent potential transmission to humans. After the vaccine was released in 2012, uptake by horse owners was slow, with some estimated 11-17% of horses in Australia vaccinated. This study was commissioned to examine barriers to vaccine uptake and potential drivers to future adoption of vaccination by horse owners. This study examined qualitative comments from respondents to an on-line survey, reporting reasons for not vaccinating their horses. The study also investigated scenarios in which respondents felt they might consider vaccinating their horses. Self-reported barriers to uptake of the Hendra virus vaccine by horse owners (N = 150) included concerns about vaccine safety, cost, and effectiveness. Reduction in vaccination costs and perception of immediacy of Hendra virus risk were reported as being likely to change future behaviour. However, the data also indicated that horse owners generally would not reconsider vaccinating their horses if advised by their veterinarian. While changes to vaccine costs and the availability data supporting vaccine safety and efficacy may encourage more horse owners to vaccinate, this study highlights the importance of protecting the relationship between veterinarians and horse owners within the risk management strategies around Hendra virus. Interactions and trust between veterinarians and animal owners has important implications for management of and

Patent data mining: a tool for accelerating HIV vaccine innovation.

PubMed

Clark, K; Cavicchi, J; Jensen, K; Fitzgerald, R; Bennett, A; Kowalski, S P

2011-05-31

Global access to advanced vaccine technologies is challenged by the interrelated components of intellectual property (IP) management strategies, technology transfer (legal and technical) capabilities and the capacity necessary for accelerating R&D, commercialization and delivery of vaccines. Due to a negative association with the management of IP, patents are often overlooked as a vast resource of freely available, information akin to scientific journals as well as business and technological information and trends fundamental for formulating policies and IP management strategies. Therefore, a fundamental step towards facilitating global vaccine access will be the assembly, organization and analysis of patent landscapes, to identify the amount of patenting, ownership (assignees) and fields of technology covered. This is critical for making informed decisions (e.g., identifying licensees, building research and product development collaborations, and ascertaining freedom to operate). Such information is of particular interest to the HIV vaccine community where the HIV Vaccine Enterprise, have voiced concern that IP rights (particularly patents and trade secrets) may prevent data and materials sharing, delaying progress in research and development of a HIV vaccine. We have compiled and analyzed a representative HIV vaccine patent landscape for a prime-boost, DNA/adenoviral vaccine platform, as an example for identifying obstacles, maximizing opportunities and making informed IP management strategy decisions towards the development and deployment of an efficacious HIV vaccine. Copyright © 2011 Elsevier Ltd. All rights reserved.

Human Papillomavirus Vaccine Uptake among Individuals with Systemic Inflammatory Diseases

PubMed Central

Feldman, Candace H.; Hiraki, Linda T.; Lii, Huichuan; Seeger, John D.; Kim, Seoyoung C.

2015-01-01

Objectives The human papillomavirus (HPV) vaccine is safe and efficacious in patients with systemic inflammatory diseases (SID) who have higher rates of persistent HPV infection. We compared HPV vaccine uptake among SID and non-SID patients. Methods Using a U.S. insurance claims database (2006–2012), we identified individuals 9–26 years with ≥2 SID diagnosis codes ≥7 days apart with ≥12 months of continuous enrollment prior to the second code (index date). We matched SID patients by age, sex and index date to randomly selected non-SID subjects and selected those with ≥24 months of post-index date continuous follow-up. We also identified a non-SID subcohort with ≥1 diagnosis code for asthma. We defined initiation as ≥1 HPV vaccination claim after 2007, and completion as 3 claims. We used multivariable logistic regression to assess uptake in females 11–26 years comparing SID, non-SID and asthma cohorts, adjusting for demographics, region, comorbidities, and healthcare utilization. Results We identified 5,642 patients 9–26 years with SID and 20,643 without. The mean age was 18.1 years (SD 4.9). We identified 1,083 patients with asthma; the mean age was 17.2 (SD 5.1). Among females, 20.6% with SID, 23.1% without SID and 22.9% with asthma, received ≥1 HPV vaccine. In our adjusted models, the odds of receipt of ≥1 vaccine was 0.87 times lower in SID (95% CI 0.77–0.98) compared to non-SID and did not differ for 3 vaccines (OR 1.03, 95% CI 0.83–1.26). The odds of initiation and completion were not statistically different between SID and non-SID asthma cohorts. Conclusions In this nationwide cohort, HPV vaccine uptake was extremely low. Despite the heightened risk of persistent HPV infection among those with SID, no increase in HPV vaccine uptake was observed. Public health efforts to promote HPV vaccination overall are needed, and may be particularly beneficial for those at higher risk. PMID:25692470

The development of global vaccine stockpiles

PubMed Central

Yen, Catherine; Hyde, Terri B; Costa, Alejandro J; Fernandez, Katya; Tam, John S; Hugonnet, Stéphane; Huvos, Anne M; Duclos, Philippe; Dietz, Vance J; Burkholder, Brenton T

2016-01-01

Global vaccine stockpiles, in which vaccines are reserved for use when needed for emergencies or supply shortages, have effectively provided countries with the capacity for rapid response to emergency situations, such as outbreaks of yellow fever and meningococcal meningitis. The high cost and insufficient supply of many vaccines, including oral cholera vaccine and pandemic influenza vaccine, have prompted discussion on expansion of the use of vaccine stockpiles to address a wider range of emerging and re-emerging diseases. However, the decision to establish and maintain a vaccine stockpile is complex and must take account of disease and vaccine characteristics, stockpile management, funding, and ethical concerns, such as equity. Past experience with global vaccine stockpiles provide valuable information about the processes for their establishment and maintenance. In this Review we explored existing literature and stockpile data to discuss the lessons learned and to inform the development of future vaccine stockpiles. PMID:25661473

Treatment with belimumab in systemic lupus erythematosus does not impair antibody response to 13-valent pneumococcal conjugate vaccine.

PubMed

Nagel, J; Saxne, T; Geborek, P; Bengtsson, A A; Jacobsen, S; Svaerke Joergensen, C; Nilsson, J-Å; Skattum, L; Jönsen, A; Kapetanovic, M C

2017-09-01

Background/purpose The objective of this study was to explore the impact of systemic lupus erythematosus and belimumab given in addition to standard of care therapy on 13-valent conjugated pneumococcal vaccine (PCV13) response. Methods Forty-seven systemic lupus erythematosus patients and 21 healthy controls were immunized with a single dose of 13-valent conjugated pneumococcal vaccine. Forty systemic lupus erythematosus patients were treated with traditional disease-modifying anti rheumatic drugs, 11 of those received belimumab in addition, and 32 patients were treated with concomitant prednisolone. Quantification of serotype specific IgG levels to 12 pneumococcal capsular polysaccharides was performed in serum taken before and four to six weeks after vaccination using multiplex fluorescent microsphere immunoassay. IgG levels against serotypes 23F and 6B were also analyzed using standard enzyme-linked immunosorbent assays. Opsonophagocytic assay was performed on serotype 23F to evaluate the functionality of the antibodies. Pre- and post-vaccination log transformed antibody levels were compared to determine the impact of systemic lupus erythematosus diagnosis and different treatments on antibody response. Results Systemic lupus erythematosus patients as a group showed lower post-vaccination antibody levels and lower fold increase of antibody levels after vaccination compared to controls ( p = 0.02 and p = 0.009, respectively). Systemic lupus erythematosus patients treated with belimumab in addition to standard of care therapy or with only hydroxychloroquine did not differ compared to controls, whereas the other treatment groups had significantly lower fold increase of post-vaccination antibody levels. Higher age was associated with lower post-vaccination antibody levels among systemic lupus erythematosus patients. Conclusion Belimumab given in addition to traditional disease-modifying anti rheumatic drugs or prednisolone did not further impair antibody

Vaccine Safety

MedlinePlus

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Vaccination and allergy.

PubMed

Rottem, Menachem; Shoenfeld, Yehuda

2004-06-01

Vaccines have had a major effect on controlling the spread of infectious diseases, but use of certain vaccines was linked to potential allergic and autoimmune side effects in healthy and often in certain high-risk populations. In this review the authors summarize the current knowledge of such risks. Immediate systemic allergic reactions after vaccination with commonly used vaccines are extremely rare. Use of certain vaccines was linked to potential allergic side effects in healthy and often in certain high-risk populations. The authors review the data on the risk associated with important vaccines including influenza, smallpox, pneumococcus, Japanese encephalitis, Bacille Calmette-Guerin, pertussis, and measles, mumps, and rubella. Two main components were identified as a source for allergic reactions in vaccines: gelatin and egg protein. There is growing interest in the potential interactions between infant vaccination and risk for development of atopic disease. In addition, there is concern that genetic risk for atopy influences capacity to respond to vaccination during infancy. There is no evidence that vaccines such as Bacille Calmette-Guerin; pertussis; influenza; measles, mumps, and rubella; or smallpox have an effect on the risk of the development of atopy later in life. Immunotherapy provides an efficacious and safe method for the treatment of allergic conditions by immunomodulation of the immune system. The possibility of vaccination triggering or unmasking autoimmunity in genetically susceptible individuals cannot be ruled out, but for the general population the risk-to-benefit ratio is overwhelmingly in favor of vaccinations. Childhood vaccination remains an essential part of child health programs and should not be withheld, even from children predisposed to allergy. Vaccinations are safe, but special attention should be taken in high-risk individuals with anaphylactic reactions to foods, and in patients with autoimmune diseases.

[Conjugated vaccines].

PubMed

Fritzell, Bernard

2005-01-01

Encapsulated bacterial pathogens (e.g. Haemophilus influenzae type b [Hib], Neisseria meningitidis, or Streptococcus pneumoniae) target infants and young children who have lost any protective anti-capsular antibodies supplied maternally and whose immune systems are ineffective against T-independent antigens such as the polysaccharides of the capsule. The polysaccharide-protein conjugate vaccines overcome this limitation by converting the polysaccharide to a T-dependent antigen, which allows a vaccinated infant to mount a protective immune response. Where conjugated vaccines have been introduced into paediatric vaccination schedules, the incidence of invasive diseases caused by Hib, the group C meningococcus, or the pneumococcus has plummeted by at least 80%, a major public health success. Furthermore, surveillance has demonstrated that the conjugate vaccines provide 'herd protection' through their beneficial impact on nasopharyngeal colonisation among vaccinated children. Promising future approaches include enhancement of the number of capsular serogroups targeted by the meningococcal or pneumococcal conjugate vaccines.

A Review of Intra- and Extracellular Antigen Delivery Systems for Virus Vaccines of Finfish

PubMed Central

Munang'andu, Hetron Mweemba; Evensen, Øystein

2015-01-01

Vaccine efficacy in aquaculture has for a long time depended on evaluating relative percent survival and antibody responses after vaccination. However, current advances in vaccine immunology show that the route in which antigens are delivered into cells is deterministic of the type of adaptive immune response evoked by vaccination. Antigens delivered by the intracellular route induce MHC-I restricted CD8+ responses while antigens presented through the extracellular route activate MHC-II restricted CD4+ responses implying that the route of antigen delivery is a conduit to induction of B- or T-cell immune responses. In finfish, different antigen delivery systems have been explored that include live, DNA, inactivated whole virus, fusion protein, virus-like particles, and subunit vaccines although mechanisms linking these delivery systems to protective immunity have not been studied in detail. Hence, in this review we provide a synopsis of different strategies used to administer viral antigens via the intra- or extracellular compartments. Further, we highlight the differences in immune responses induced by antigens processed by the endogenous route compared to exogenously processed antigens. Overall, we anticipate that the synopsis put together in this review will shed insights into limitations and successes of the current vaccination strategies used in finfish vaccinology. PMID:26065009

Safe use of vaccines and vaccine compliance with food safety requirements.

PubMed

Grein, K; Papadopoulos, O; Tollis, M

2007-08-01

Advanced technologies and regulatory regimes have contributed to the availability of veterinary vaccines that have high quality and favourable safety profiles in terms of potential risks posed to the target animals, the persons who come into contact with the vaccine, the consumers of food derived from vaccinated animals and the environment. The authorisation process requires that a range of safety studies are provided to evaluate the products. The design and production of vaccines, and their safe use, are primarily assessed by using data gathered from extensive pre-marketing studies performed on target animals and specific quality tests. The current post-marketing safeguards include good manufacturing practices, batch safety testing, inspections and pharmacovigilance. In addition to hazard identification, a full benefit/risk evaluation needs to be undertaken. The outcome of that evaluation will determine options for risk management and affect regulatory decisions on the safety of the vaccine; options might, for example, include special warnings on package inserts and labels.

Modeling vaccination in a heterogeneous metapopulation system

NASA Astrophysics Data System (ADS)

Lachiany, Menachem

2016-09-01

We present here a multicity SIS epidemic model with vaccination. The model describes the dynamics of heterogeneous metapopulations that contain imperfectly vaccinated individuals. The effect of vaccination on heterogeneous multicity models has not been previously studied. We show that under very generic conditions, the epidemic threshold does not depend on the diffusion coefficient of the vaccinated individuals, but it does depend on the diffusion coefficient of the infected population. We then show, using a novel methodology, that the reproduction number is determined by the homogeneous model parameters and by the maximal number of neighbors a city can have, when the diffusion coefficient of the infected population is low. Finally, we present numerical simulations to support the analytical results.

An economic evaluation of contingency management for completion of hepatitis B vaccination in those on treatment for opiate dependence.

PubMed

Rafia, Rachid; Dodd, Peter J; Brennan, Alan; Meier, Petra S; Hope, Vivian D; Ncube, Fortune; Byford, Sarah; Tie, Hiong; Metrebian, Nicola; Hellier, Jennifer; Weaver, Tim; Strang, John

2016-09-01

To determine whether the provision of contingency management using financial incentives to improve hepatitis B vaccine completion in people who inject drugs entering community treatment represents a cost-effective use of health-care resources. A probabilistic cost-effectiveness analysis was conducted, using a decision-tree to estimate the short-term clinical and health-care cost impact of the vaccination strategies, followed by a Markov process to evaluate the long-term clinical consequences and costs associated with hepatitis B infection. Data on attendance to vaccination from a UK cluster randomized trial. Two contingency management options were examined in the trial: fixed versus escalating schedule financial incentives. Life-time health-care costs and quality-adjusted life years discounted at 3.5% annually; incremental cost-effectiveness ratios. The resulting estimate for the incremental life-time health-care cost of the contingency management strategy versus usual care was £21.86 [95% confidence interval (CI) = -£12.20 to 39.86] per person offered the incentive. For 1000 people offered the incentive, the incremental reduction in numbers of hepatitis B infections avoided over their lifetime was estimated at 19 (95% CI = 8-30). The probabilistic incremental cost per quality adjusted life-year gained of the contingency management programme was estimated to be £6738 (95% CI = £6297-7172), with an 89% probability of being considered cost-effective at a threshold of £20 000 per quality-adjusted life years gained (97.60% at £30 000). Using financial incentives to increase hepatitis B vaccination completion in people who inject drugs could be a cost-effective use of health-care resources in the UK as long as the incidence remains above 1.2%. © 2016 Society for the Study of Addiction.

Quadrivalent human papillomavirus vaccine and autoimmune adverse events: a case-control assessment of the vaccine adverse event reporting system (VAERS) database.

PubMed

Geier, David A; Geier, Mark R

2017-02-01

Gardasil is a quadrivalent human papillomavirus (HPV4) vaccine that was approved for use by the US Food and Drug Administration in June 2006. HPV4 vaccine is routinely recommended for administration to women in the USA who are 11-12 years old by the Advisory Committee on Immunization Practices. Previous studies suggest HPV4 vaccine administration was associated with autoimmune diseases. As a consequence, an epidemiological assessment of the vaccine adverse event reporting system database was undertaken for adverse event reports associated with vaccines administered from 2006 to 2014 to 6-39 year-old recipients with a listed US residence and a specified female gender. Cases with the serious autoimmune adverse event (SAAE) outcomes of gastroenteritis (odds ratio (OR) 4.627, 95 % confidence interval (CI) 1.892-12.389), rheumatoid arthritis (OR 5.629, 95 % CI 2.809-12.039), thrombocytopenia (OR 2.178, 95 % CI 1.222-3.885), systemic lupus erythematosus (OR 7.626, 95 % CI 3.385-19.366), vasculitis (OR 3.420, 95 % CI 1.211-10.408), alopecia (OR 8.894, 95 % CI 6.255-12.914), CNS demyelinating conditions (OR 1.585, 95 % CI 1.129-2.213), ovarian damage (OR 14.961, 95 % CI 6.728-39.199), or irritable bowel syndrome (OR 10.021, 95 % CI 3.725-33.749) were significantly more likely than controls to have received HPV4 vaccine (median onset of initial symptoms ranged from 3 to 37 days post-HPV4 vaccination). Cases with the outcome of Guillain-Barre syndrome (OR 0.839, 95 % CI 0.601-1.145) were no more likely than controls to have received HPV4 vaccine. In addition, cases with the known HPV4-related outcome of syncope were significantly more likely than controls to have received HPV4 vaccine (OR 5.342, 95 % CI 4.942-5.777). Cases with the general health outcomes of infection (OR 0.765, 95 % CI 0.428-1.312), conjunctivitis (OR 1.010, 95 % CI 0.480-2.016), diarrhea (OR 0.927, 95 % CI 0.809-1.059), or pneumonia (OR 0.785, 95 % CI 0.481-1.246) were no more likely

Use of a current varicella vaccine as a live polyvalent vaccine vector.

PubMed

Murakami, Kouki; Mori, Yasuko

2016-01-04

Varicella-zoster virus (VZV) is the causative agent of varicella and zoster. The varicella vaccine was developed to control VZV infection in children. The currently available Oka vaccine strain is the only live varicella vaccine approved by the World Health Organization. We previously cloned the complete genome of the Oka vaccine strain into a bacterial artificial chromosome vector and then successfully reconstituted the virus. We then used this system to generate a recombinant Oka vaccine virus expressing mumps virus gene(s). The new recombinant vaccine may be an effective polyvalent live vaccine that provides protection against both varicella and mumps viruses. In this review, we discussed about possibility of polyvalent live vaccine(s) using varicella vaccine based on our recent studies. Copyright © 2014 Elsevier Ltd. All rights reserved.

Awareness among adults of vaccine-preventable diseases and recommended vaccinations, United States, 2015.

PubMed

Lu, Peng-Jun; O'Halloran, Alissa; Kennedy, Erin D; Williams, Walter W; Kim, David; Fiebelkorn, Amy Parker; Donahue, Sara; Bridges, Carolyn B

2017-05-25

increase uptake of recommended vaccines, such as patient reminder/recall systems and other healthcare system-based interventions, and ensuring patients' vaccination needs are assessed, are needed to improve vaccination of adults. Published by Elsevier Ltd.

Pharmacogenomics in the preclinical development of vaccines: evaluation of efficacy and systemic toxicity in the mouse using array technology.

PubMed

Regnström, Karin J

2008-01-01

The development of vaccines, conventional protein based as well as nucleic acid based vaccines, and their delivery systems has been largely empirical and ineffective. This is partly due to a lack of methodology, since traditionally only a few markers are studied. By introducing gene expression analysis and bioinformatics into the design of vaccines and their delivery systems, vaccine development can be improved and accelerated considerably. Each vaccine antigen and delivery system combination is characterized by a unique genomic profile, a "fingerprint" that will give information of not only immunological and toxicological responses but also other related cellular responses e.g. cell cycle, apoptosis and carcinogenic effects. The resulting unique genomic fingerprint facilitates the establishment of molecular structure--pharmacological activity relationships and therefore leads to optimization of vaccine development.

Vaccine delivery to the oral cavity using coated microneedles induces systemic and mucosal immunity

PubMed Central

Ma, Yunzhe; Tao, Wenqian; Krebs, Shelly J.; Sutton, William F.; Haigwood, Nancy L.; Gill, Harvinder S.

2014-01-01

Purpose The objective of this study is to evaluate the feasibility of using coated microneedles to deliver vaccines into the oral cavity to induce systemic and mucosal immune responses. Method Microneedles were coated with sulforhodamine, ovalbumin and two HIV antigens. Coated microneedles were inserted into the inner lower lip and dorsal surface of the tongue of rabbits. Histology was used to confirm microneedle insertion, and systemic and mucosal immune responses were characterized by measuring antigen-specific immunoglobulin G (IgG) in serum and immunoglobulin A (IgA) in saliva, respectively. Results Histological evaluation of tissues shows that coated microneedles can penetrate the lip and tongue to deliver coatings. Using ovalbumin as a model antigen it was found that the lip and the tongue are equally immunogenic sites for vaccination. Importantly, both sites also induced a significant (p < 0.05) secretory IgA in saliva compared to pre-immune saliva. Microneedle-based oral cavity vaccination was also compared to the intramuscular route using two HIV antigens, a virus-like particle and a DNA vaccine. Microneedle-based delivery to the oral cavity and the intramuscular route exhibited similar (p > 0.05) yet significant (p < 0.05) levels of antigen-specific IgG in serum. However, only the microneedle-based oral cavity vaccination group stimulated a significantly higher (p < 0.05) antigen-specific IgA response in saliva, but not intramuscular injection. Conclusion In conclusion, this study provides a novel method using microneedles to induce systemic IgG and secretory IgA in saliva, and could offer a versatile technique for oral mucosal vaccination. PMID:24623480

Adverse events following quadrivalent meningococcal CRM-conjugate vaccine (Menveo®) reported to the Vaccine Adverse Event Reporting system (VAERS), 2010-2015.

PubMed

Myers, Tanya R; McNeil, Michael M; Ng, Carmen S; Li, Rongxia; Lewis, Paige W; Cano, Maria V

2017-03-27

Limited data are available describing the post-licensure safety of meningococcal vaccines, including Menveo®. We reviewed reports of adverse events (AEs) to the Vaccine Adverse Event Reporting System (VAERS) to assess safety in all age groups. VAERS is a national spontaneous vaccine safety surveillance system co-administered by the Centers for Disease Control and Prevention and the US Food and Drug Administration. We searched the VAERS database for US reports of adverse events in persons who received Menveo from 1 January 2010 through 31 December 2015. We clinically reviewed reports and available medical records for serious AEs, selected pre-specified outcomes, and vaccination during pregnancy. We used empirical Bayesian data mining to identify AEs that were disproportionately reported after receipt of Menveo. During the study period, VAERS received 2614 US reports after receipt of Menveo. Of these, 67 were classified as serious, including 1 report of death. Adolescents (aged 11-18years) accounted for 74% of reports. Most of the reported AEs were non-serious and described AEs consistent with data from pre-licensure studies. Anaphylaxis and syncope were the two most common events in the serious reports. We did not identify any new safety concerns after review of AEs that exceeded the data mining threshold, although we did observe disproportionate reporting for terms that were not associated with an adverse event (e.g., "incorrect drug dosage form administered", "wrong technique in drug usage process"). Although reports were limited, we did not find any evidence for concern regarding the use of Menveo during pregnancy. In our review of VAERS reports, findings of AEs were consistent with the data from pre-licensure studies. Vaccine providers should continue to emphasize and adhere to proper administration of the vaccine. Copyright © 2017 Elsevier Ltd. All rights reserved.

Novel transgenic rice-based vaccines.

PubMed

Azegami, Tatsuhiko; Itoh, Hiroshi; Kiyono, Hiroshi; Yuki, Yoshikazu

2015-04-01

Oral vaccination can induce both systemic and mucosal antigen-specific immune responses. To control rampant mucosal infectious diseases, the development of new effective oral vaccines is needed. Plant-based vaccines are new candidates for oral vaccines, and have some advantages over the traditional vaccines in cost, safety, and scalability. Rice seeds are attractive for vaccine production because of their stability and resistance to digestion in the stomach. The efficacy of some rice-based vaccines for infectious, autoimmune, and other diseases has been already demonstrated in animal models. We reported the efficacy in mice, safety, and stability of a rice-based cholera toxin B subunit vaccine called MucoRice-CTB. To advance MucoRice-CTB for use in humans, we also examined its efficacy and safety in primates. The potential of transgenic rice production as a new mucosal vaccine delivery system is reviewed from the perspective of future development of effective oral vaccines.

Vaxjo: a web-based vaccine adjuvant database and its application for analysis of vaccine adjuvants and their uses in vaccine development.

PubMed

Sayers, Samantha; Ulysse, Guerlain; Xiang, Zuoshuang; He, Yongqun

2012-01-01

Vaccine adjuvants are compounds that enhance host immune responses to co-administered antigens in vaccines. Vaxjo is a web-based central database and analysis system that curates, stores, and analyzes vaccine adjuvants and their usages in vaccine development. Basic information of a vaccine adjuvant stored in Vaxjo includes adjuvant name, components, structure, appearance, storage, preparation, function, safety, and vaccines that use this adjuvant. Reliable references are curated and cited. Bioinformatics scripts are developed and used to link vaccine adjuvants to different adjuvanted vaccines stored in the general VIOLIN vaccine database. Presently, 103 vaccine adjuvants have been curated in Vaxjo. Among these adjuvants, 98 have been used in 384 vaccines stored in VIOLIN against over 81 pathogens, cancers, or allergies. All these vaccine adjuvants are categorized and analyzed based on adjuvant types, pathogens used, and vaccine types. As a use case study of vaccine adjuvants in infectious disease vaccines, the adjuvants used in Brucella vaccines are specifically analyzed. A user-friendly web query and visualization interface is developed for interactive vaccine adjuvant search. To support data exchange, the information of vaccine adjuvants is stored in the Vaccine Ontology (VO) in the Web Ontology Language (OWL) format.

Vaxjo: A Web-Based Vaccine Adjuvant Database and Its Application for Analysis of Vaccine Adjuvants and Their Uses in Vaccine Development

PubMed Central

Sayers, Samantha; Ulysse, Guerlain; Xiang, Zuoshuang; He, Yongqun

2012-01-01

Vaccine adjuvants are compounds that enhance host immune responses to co-administered antigens in vaccines. Vaxjo is a web-based central database and analysis system that curates, stores, and analyzes vaccine adjuvants and their usages in vaccine development. Basic information of a vaccine adjuvant stored in Vaxjo includes adjuvant name, components, structure, appearance, storage, preparation, function, safety, and vaccines that use this adjuvant. Reliable references are curated and cited. Bioinformatics scripts are developed and used to link vaccine adjuvants to different adjuvanted vaccines stored in the general VIOLIN vaccine database. Presently, 103 vaccine adjuvants have been curated in Vaxjo. Among these adjuvants, 98 have been used in 384 vaccines stored in VIOLIN against over 81 pathogens, cancers, or allergies. All these vaccine adjuvants are categorized and analyzed based on adjuvant types, pathogens used, and vaccine types. As a use case study of vaccine adjuvants in infectious disease vaccines, the adjuvants used in Brucella vaccines are specifically analyzed. A user-friendly web query and visualization interface is developed for interactive vaccine adjuvant search. To support data exchange, the information of vaccine adjuvants is stored in the Vaccine Ontology (VO) in the Web Ontology Language (OWL) format. PMID:22505817

Communication about vaccinations in Italian websites: a quantitative analysis.

PubMed

Tafuri, Silvio; Gallone, Maria S; Gallone, Maria F; Zorico, Ivan; Aiello, Valeria; Germinario, Cinzia

2014-01-01

Babies' parents and people who look for information about vaccination often visit anti-vaccine movement's websites, blogs by naturopathic physicians or natural and alternative medicine practitioners. The aim of this work is to provide a quantitative analysis on the type of information available to Italian people regarding vaccination and a quality analysis of websites retrieved through our searches. A quality score was created to evaluate the technical level of websites. A research was performed through Yahoo, Google, and MSN using the keywords "vaccine" and "vaccination," with the function "OR" in order to identify the most frequently used websites. The 2 keywords were input in Italian, and the first 15 pages retrieved by each search engine were analyzed. 149 websites were selected through this methodology. Fifty-three per cent of the websites belonged to associations, groups, or scientific companies, 32.2% (n = 48) consisted of a personal blog and 14.8% (n = 22) belonged to some of the National Health System offices. Among all analyzed websites, 15.4% (n = 23) came from anti-vaccine movement groups. 37.6% reported webmaster name, 67.8% webmaster e-mail, 28.6% indicated the date of the last update and 46.6% the author's name. The quality score for government sites was higher on average than anti-vaccine websites; although, government sites don't use Web 2.0 functions, as the forums.: National Health System institutions who have to promote vaccination cannot avoid investing in web communication because it cannot be managed by private efforts but must be the result of Public Health, private and scientific association, and social movement synergy.

Biotechnology and DNA vaccines for aquatic animals

USGS Publications Warehouse

Kurath, G.

2008-01-01

Biotechnology has been used extensively in the development of vaccines for aquaculture. Modern molecular methods such as polymerase chain reaction (PCR), cloning and microarray analysis have facilitated antigen discovery, construction of novel candidate vaccines, and assessments of vaccine efficacy, mode of action, and host response. This review focuses on DNA vaccines for finfish to illustrate biotechnology applications in this field. Although DNA vaccines for fish rhabdoviruses continue to show the highest efficacy, DNA vaccines for several other viral and bacterial fish pathogens have now been proven to provide significant protection against pathogen challenge. Studies of the fish rhabdovirus DNA vaccines have elucidated factors that affect DNA vaccine efficacy as well as the nature of the fish innate and adaptive immune responses to DNA vaccines. As tools for managing aquatic animal disease emergencies, DNA vaccines have advantages in speed, flexibility, and safety, and one fish DNA vaccine has been licensed.

Newcastle disease virus vectored vaccines as bivalent or antigen delivery vaccines

PubMed Central

2017-01-01

Recent advances in reverse genetics techniques make it possible to manipulate the genome of RNA viruses such as Newcastle disease virus (NDV). Several NDV vaccine strains have been used as vaccine vectors in poultry, mammals, and humans to express antigens of different pathogens. The safety, immunogenicity, and protective efficacy of these NDV-vectored vaccines have been evaluated in pre-clinical and clinical studies. The vaccines are safe in mammals, humans, and poultry. Bivalent NDV-vectored vaccines against pathogens of economic importance to the poultry industry have been developed. These bivalent vaccines confer solid protective immunity against NDV and other foreign antigens. In most cases, NDV-vectored vaccines induce strong local and systemic immune responses against the target foreign antigen. This review summarizes the development of NDV-vectored vaccines and their potential use as a base for designing other effective vaccines for veterinary and human use. PMID:28775971

Chinese vaccine products go global: vaccine development and quality control.

PubMed

Xu, Miao; Liang, Zhenglun; Xu, Yinghua; Wang, Junzhi

2015-05-01

Through the continuous efforts of several generations, China has become one of the few countries in the world that is capable of independently addressing all the requirements by the Expanded Program on Immunization. Regulatory science is applied to continuously improve the vaccine regulatory system. Passing the prequalification by WHO has allowed Chinese vaccine products to go global. Chinese vaccine products not only secure disease prevention and control domestically but also serve the needs for international public health. This article describes the history of Chinese vaccine development, the current situation of Chinese vaccine industry and its contribution to the prevention and control of infectious diseases. We also share our experience of national quality control and vaccine regulation during the past decades. China's experience in vaccine development and quality control can benefit other countries and regions worldwide, including the developing countries.

The impact of new vaccine introduction on the coverage of existing vaccines: a cross-national, multivariable analysis.

PubMed

Shearer, Jessica C; Walker, Damian G; Risko, Nicholas; Levine, Orin S

2012-12-14

A surge of new and underutilized vaccine introductions into national immunization programmes has called into question the effect of new vaccine introduction on immunization and health systems. In particular, countries deciding whether to introduce a new or underutilized vaccine into their routine immunization programme may query possible effects on the delivery and coverage of existing vaccines. Using coverage of diphtheria-tetanus-pertussis (DTP) vaccine as a proxy for immunization system performance, this study aims to test whether new vaccine introduction into national immunization programs was associated with changes in coverage of three doses of DTP vaccine among infants. DTP3 vaccine coverage was analyzed in 187 countries during 1999-2009 using multivariable cross-national mixed-effect longitudinal models. Controlling for other possible determinants of DTP3 coverage at the national level these models found minimal association between the introduction of Hepatitis-, Haemophilus influenzae type b-, and rotavirus-containing vaccines and DTP3 coverage. Instead, frequent and sometimes large fluctuations in coverage are associated with other development and health systems variables, including the presence of armed conflict, coverage of antenatal care services, infant mortality, the percent of health expenditures that are private and total health expenditures per capita. Introductions of new vaccines did not affect national coverage of DTP3 vaccine in the countries studied. Introductions of other new vaccines and multiple vaccine introductions should be monitored for immunization and health systems impacts. Copyright © 2012 Elsevier Ltd. All rights reserved.

Evaluation of a vaccine passport to improve vaccine coverage in people living with HIV.

PubMed

Chadwick, D R; Corbett, K; Mann, S; Teruzzi, B; Horner, S

2018-01-01

An increased risk of vaccine-preventable infections (VPIs) is seen in people living with HIV (PLWH), and current vaccine coverage and immunity is variable. Vaccine passports have the potential to improve vaccine coverage. The objective was to assess how successful a vaccine passport was in improving vaccine coverage in PLWH. Baseline immunity to VPIs was established in PLWH attending a single HIV clinic and vaccinations required were determined based on the BHIVA Vaccination Guidelines (2015). The passport was completed and the PLWH informed about additional vaccines they should obtain from primary care. After 6-9 months the passport was reviewed including confirmation if vaccines were given. PLWH satisfaction with the system was evaluated by a survey. Seventy-three PLWH provided sufficient data for analysis. At baseline significant proportions of PLWH were not immune/unvaccinated to the main VPIs, especially human papillomavirus, pneumococcus and measles. After the passport was applied immunity improved significantly (56% overall, p < 0.01) for most VPIs; however, full coverage was not achieved. The system was popular with PLWH. The passport was successful in increasing vaccination coverage although full or near-full coverage was not achieved. A more successful service would probably be achieved by commissioning English HIV clinics to provide all vaccines.

DNA Vaccination Against Metastatic Breast Cancer

DTIC Science & Technology

2002-07-01

Although DNA vaccines have shown effectiveness in clinical trials , it is essential to demonstrate pre- clinical effectiveness for anti-tumor DNA vaccines...been shown to induce strong anti-tumor immunity in mice (3). Although gene vaccines have shown effectiveness in clinical trials for infectious...stronger justification for a clinical trial . REFERENCES: 1. Fornier, M., P. Munster, and A. D. Seidman. 1999. Update on the management of advanced breast

Disposing of Excess Vaccines After the Withdrawal of Oral Polio Vaccine

PubMed Central

Ramirez Gonzalez, Alejandro; Dolan, Samantha B.; Garon, Julie; Veira, Chantal Laroche; Hampton, Lee M.; Chang Blanc, Diana; Patel, Manish M.

2017-01-01

Abstract Until recently, waste management for national immunization programs was limited to sharps waste, empty vaccine vials, or vaccines that had expired or were no longer usable. However, because wild-type 2 poliovirus has been eradicated, the World Health Organization’s (WHO’s) Strategic Advisory Group of Experts on Immunization deemed that all countries must simultaneously cease use of the type 2 oral polio vaccine and recommended that all countries and territories using oral polio vaccine (OPV) “switch” from trivalent OPV (tOPV; types 1, 2, and 3 polioviruses) to bivalent OPV (bOPV; types 1 and 3 polioviruses) during a 2-week period in April 2016. Use of tOPV after the switch would risk outbreaks of paralysis related to type 2–circulating vaccine-derived poliovirus (cVDPV2). To minimize risk of vaccine-derived polio countries using OPV were asked to dispose of all usable, unexpired tOPV after the switch to bOPV. In this paper, we review the rationale for tOPV disposal and describe the global guidelines provided to countries for the safe and appropriate disposal of tOPV. These guidelines gave countries flexibility in implementing this important task within the confines of their national regulations, capacities, and resources. Steps for appropriate disposal of tOPV included removal of all tOPV vials from the cold chain, placement in appropriate bags or containers, and disposal using a recommended approach (ie, autoclaving, boiling, chemical inactivation, incineration, or encapsulation) followed by burial or transportation to a designated waste facility. This experience with disposal of tOPV highlights the adaptability of national immunization programs to new procedures, and identifies gaps in waste management policies and strategies with regard to disposal of unused vaccines. The experience also provides a framework for future policies and for developing programmatic guidance for the ultimate disposal of all OPV after the eradication of polio. PMID

Influenza Vaccination Strategies: Comparing Inactivated and Live Attenuated Influenza Vaccines

PubMed Central

Sridhar, Saranya; Brokstad, Karl A.; Cox, Rebecca J.

2015-01-01

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

The development of global vaccine stockpiles.

PubMed

Yen, Catherine; Hyde, Terri B; Costa, Alejandro J; Fernandez, Katya; Tam, John S; Hugonnet, Stéphane; Huvos, Anne M; Duclos, Philippe; Dietz, Vance J; Burkholder, Brenton T

2015-03-01

Global vaccine stockpiles, in which vaccines are reserved for use when needed for emergencies or supply shortages, have effectively provided countries with the capacity for rapid response to emergency situations, such as outbreaks of yellow fever and meningococcal meningitis. The high cost and insufficient supply of many vaccines, including oral cholera vaccine and pandemic influenza vaccine, have prompted discussion on expansion of the use of vaccine stockpiles to address a wider range of emerging and re-emerging diseases. However, the decision to establish and maintain a vaccine stockpile is complex and must take account of disease and vaccine characteristics, stockpile management, funding, and ethical concerns, such as equity. Past experience with global vaccine stockpiles provide valuable information about the processes for their establishment and maintenance. In this Review we explored existing literature and stockpile data to discuss the lessons learned and to inform the development of future vaccine stockpiles. Copyright © 2015 World Health Organization. Published by Elsevier Ltd/Inc/BV. All rights reserved. Published by Elsevier Ltd. All rights reserved.

[From new vaccine to new target: revisiting influenza vaccination].

PubMed

Gérard, M

2011-09-01

Annual vaccination is since many years the corner stone of Influenza control strategy. Because conventional vaccine are needle-based, are less immunogenic in old people and induce only systemic IgG production, intranasal and intradermal vaccines that are recently or will be soon available in Belgium will offer distinct advantages. Intradermal vaccination is on the Belgian market since 2010. A stronger immune response that allows an antigen sparing strategy is elicited because antigens are delivered near the dermal dendritic cells. Local side effects are more pronounced than after intramuscular injection. The needle-free intranasal vaccine that has been approved for use in people less than 18 years old by the EMEA in October 2010 induces also a mucosal IgA response. Improved clinical results than with intramuscular vaccine has been documented in several studies in children. Several conditions are contraindication to nasal vaccination because of patterns of side effects and because the vaccine is an live-attenuated vaccine. Pregnant women has become a top priority for Influenza vaccination in the recommendations of the High Council of Health in Belgium since the 2009 H1N1 pandemic. Several studies has since then documented the increased risk for Influenza-related morbidity in pregnant women especially during the third trimester and independently of the presence of other comorbidities. Reduced incidence of documented Influenza and of Influenza-related hospitalizations are observed in the new born of vaccinated women until 6 months of age. Availability of new vaccines for Influenza and better knowledge of the benefit of vaccination in target populations are important tools to optimize vaccine coverage of the population.

Poliovirus vaccination during the endgame: insights from integrated modeling.

PubMed

Duintjer Tebbens, Radboud J; Thompson, Kimberly M

2017-06-01

Managing the polio endgame requires access to sufficient quantities of poliovirus vaccines. After oral poliovirus vaccine (OPV) cessation, outbreaks may occur that require outbreak response using monovalent OPV (mOPV) and/or inactivated poliovirus vaccine. Areas covered: We review the experience and challenges with managing vaccine supplies in the context of the polio endgame. Building on models that explored polio endgame risks and the potential mOPV needs to stop outbreaks from live poliovirus reintroductions, we conceptually explore the potential demands for finished and bulk mOPV doses from a stockpile in the context of limited shelf-life of finished vaccine and time delays to convert bulk to finished vaccine. Our analysis suggests that the required size of the mOPV stockpile varies by serotype, with the highest expected needs for serotype 1 mOPV. Based on realizations of poliovirus risks after OPV cessation, the stockpile required to eliminate the chance of a stock-out appears considerably larger than the currently planned mOPV stockpiles. Expert commentary: The total required stockpile size depends on the acceptable probability of a stock-out, and increases with longer times to finish bulk doses and shorter shelf-lives of finished doses. Successful polio endgame management will require careful attention to poliovirus vaccine supplies.

Different applications of virus-like particles in biology and medicine: Vaccination and delivery systems.

PubMed

Shirbaghaee, Zeinab; Bolhassani, Azam

2016-03-01

Virus-like particles (VLPs) mimic the whole construct of virus particles devoid of viral genome as used in subunit vaccine design. VLPs can elicit efficient protective immunity as direct immunogens compared to soluble antigens co-administered with adjuvants in several booster injections. Up to now, several prokaryotic and eukaryotic systems such as insect, yeast, plant, and E. coli were used to express recombinant proteins, especially for VLP production. Recent studies are also generating VLPs in plants using different transient expression vectors for edible vaccines. VLPs and viral particles have been applied for different functions such as gene therapy, vaccination, nanotechnology, and diagnostics. Herein, we describe VLP production in different systems as well as its applications in biology and medicine. © 2015 Wiley Periodicals, Inc.

Vaccines of the future.

PubMed

Nossal, G J V

2011-12-30

Vaccines of the future can be divided into three broad groups, namely those of the near future (<10 years); the medium-term future (10-19 years); and the long-term future (20-50 years). For the near future, there is some "low hanging fruit" which is clearly on the horizon, such as a Vi-conjugate vaccine for typhoid or a protein-based vaccine for Neisseria meningitidis serogroup B. Just slightly more distant will be vaccines for shigellosis and a common protein vaccine for Streptococcus pneumoniae. Also in this group, but not as far advanced, will be a vaccine for Group A streptococcus. I place vaccines for the "big three", malaria, tuberculosis and HIV/AIDS in the medium term basket. The sporozoite malaria vaccine RTS-S is closest, but surely a definitive malaria vaccine will also require antigens from other stages of the life cycle. A tuberculosis vaccine will be either a re-engineered BCG; or a molecular vaccine with several protein antigens; or one based on prime-boost strategies. What will delay this is the high cost of clinical trials. For HIV/AIDS, the partial success of the Sanofi-Pasteur prime-boost vaccine has given some hope. I still place much faith in antibody-based vaccines and especially on mimotopes of the env transitional state assumed after initial CD4 binding. Monoclonal antibodies are also leading us in interesting directions. Longer term, the vaccine approach will be successful for autoimmune diseases, e.g. juvenile diabetes and coeliac disease. Cancer vaccines are also briefly surveyed. Adjunct issues needing to be addressed include more extensive combinations; alternate delivery systems; and more intelligently designed adjuvants based on knowledge of the innate immune system. Copyright © 2011. Published by Elsevier Ltd.

Experiences and lessons learned from 29 HPV vaccination programs implemented in 19 low and middle-income countries, 2009-2014.

PubMed

Ladner, Joël; Besson, Marie-Hélène; Audureau, Etienne; Rodrigues, Mariana; Saba, Joseph

2016-10-13

Cervical cancer is the greatest cause of age-weighted years of life lost in the developing world. Human papillomavirus (HPV) infection is associated with a high proportion of cervical cancers, and HPV vaccination may help to reduce the incidence of cancer. The aim of the study was to identify barriers, obstacles, and strategies and to analyze key concerns and lessons learned with respect to the implementation of HPV vaccination program in low- and middle-income countries. The Gardasil Access Program (GAP) is a donation program established to enable organizations and institutions in eligible low-resource countries to gain operational experience designing and implementing HPV vaccination programs. This study used an online survey to capture the experiences and insights of program managers participating in the GAP. Different factors related to HPV vaccination program management were collected. A mixed-method approach enabled the presentation of both quantitative measurements and qualitative insights. Twenty-nine programs implemented by 23 institutions in 19 low- and middle-income countries were included. Twenty programs managers (97.7 %) reported that their institution implemented sensitization strategies about vaccination prior to the launch of vaccination campaign. The most frequently reported obstacles to HPV vaccination by the program managers were erroneous perceptions of population related to the vaccine's safety and efficacy. Reaching and maintaining follow-up with target populations were identified as challenges. Insufficient infrastructure and human resources financing and the vaccine delivery method were identified as significant health system barriers. Coupling HPV vaccination with other health interventions for mothers of targeted girls helped to increase vaccination and cervical cancer screening. The majority of program managers reported that their programs had a positive impact on national HPV vaccination policy. The majority of institutions had

[Influenza vaccination. Effectiveness of current vaccines and future challenges].

PubMed

Ortiz de Lejarazu, Raúl; Tamames, Sonia

2015-01-01

Seasonal influenza is an annual challenge for health-care systems, due to factors such as co-circulation of 2 influenza A subtypes jointly with 2 influenza B lineages; the antigenic drift of these virus, which eludes natural immunity, as well as immunity conferred by vaccination; together with influenza impact in terms of morbidity and mortality. Influenza vaccines have been available for more than 70 years and they have progressed in formulation, production and delivery route. Recommendations on vaccination are focused on those with a higher probability of severe disease, and have a progressively wider coverage, and classically based on inactivated vaccines, but with an increasing importance of attenuated live vaccines. More inactivated vaccines are becoming available, from adyuvanted and virosomal vaccines to intradermal delivery, cell-culture or quadrivalent. Overall vaccine effectiveness is about 65%, but varies depending on characteristics of vaccines, virus, population and the outcomes to be prevented, and ranges from less than 10% to almost 90%. Future challenges are formulations that confer more extensive and lasting protection, as well as increased vaccination coverage, especially in groups such as pregnant women and health-care professionals, as well as being extended to paediatrics. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Milestones in contraceptive vaccines development and hurdles in their application

PubMed Central

Gupta, Satish Kumar; Shrestha, Abhinav; Minhas, Vidisha

2014-01-01

Contraceptive vaccines have been proposed for controlling the growing human population and wildlife population management. Multiple targets such as gonadotropin releasing hormone (GnRH), luteinizing hormone, follicle stimulating hormone, gonadotropin receptors, sperm-specific proteins and zona pellucida glycoproteins have been exploited to develop contraceptive vaccine and their efficacy investigated and shown in various experimental animal models. Vaccines based on GnRH have found application in immuno-castration of male pigs for prevention of boar-taint. Vaccines based on zona pellucida glycoproteins have shown promising results for population management of wild horses and white-tailed deer. Phase II clinical trials in women with β-human chorionic gonadotropin (β-hCG)-based contraceptive vaccine established proof of principle that these can be developed for human application. Block in fertility by β-hCG contraceptive vaccine was reversible. Further research inputs are required to establish the safety of contraceptive vaccines, improve their immunogenicity and to develop novel vaccine delivery platforms for providing long lasting immunity. PMID:24262991

Inactivated Influenza Vaccine That Provides Rapid, Innate-Immune-System-Mediated Protection and Subsequent Long-Term Adaptive Immunity.

PubMed

Chua, Brendon Y; Wong, Chinn Yi; Mifsud, Edin J; Edenborough, Kathryn M; Sekiya, Toshiki; Tan, Amabel C L; Mercuri, Francesca; Rockman, Steve; Chen, Weisan; Turner, Stephen J; Doherty, Peter C; Kelso, Anne; Brown, Lorena E; Jackson, David C

2015-10-27

The continual threat to global health posed by influenza has led to increased efforts to improve the effectiveness of influenza vaccines for use in epidemics and pandemics. We show in this study that formulation of a low dose of inactivated detergent-split influenza vaccine with a Toll-like receptor 2 (TLR2) agonist-based lipopeptide adjuvant (R4Pam2Cys) provides (i) immediate, antigen-independent immunity mediated by the innate immune system and (ii) significant enhancement of antigen-dependent immunity which exhibits an increased breadth of effector function. Intranasal administration of mice with vaccine formulated with R4Pam2Cys but not vaccine alone provides protection against both homologous and serologically distinct (heterologous) viral strains within a day of administration. Vaccination in the presence of R4Pam2Cys subsequently also induces high levels of systemic IgM, IgG1, and IgG2b antibodies and pulmonary IgA antibodies that inhibit hemagglutination (HA) and neuraminidase (NA) activities of homologous but not heterologous virus. Improved primary virus nucleoprotein (NP)-specific CD8(+) T cell responses are also induced by the use of R4Pam2Cys and are associated with robust recall responses to provide heterologous protection. These protective effects are demonstrated in wild-type and antibody-deficient animals but not in those depleted of CD8(+) T cells. Using a contact-dependent virus transmission model, we also found that heterologous virus transmission from vaccinated mice to naive mice is significantly reduced. These results demonstrate the potential of adding a TLR2 agonist to an existing seasonal influenza vaccine to improve its utility by inducing immediate short-term nonspecific antiviral protection and also antigen-specific responses to provide homologous and heterologous immunity. The innate and adaptive immune systems differ in mechanisms, specificities, and times at which they take effect. The innate immune system responds within hours of

Vaccinating my way--use of alternative vaccination schedules in New York State.

PubMed

Nadeau, Jessica A; Bednarczyk, Robert A; Masawi, Munyaradzi R; Meldrum, Megan D; Santilli, Loretta; Zansky, Shelley M; Blog, Debra S; Birkhead, Guthrie S; McNutt, Louise-Anne

2015-01-01

To identify children vaccinated following an alternative vaccine schedule using immunization information system data and determine the impact of alternative schedule use on vaccine coverage. Children born in New York State, outside New York City, between January 1, 2009 and August 14, 2011 were assessed for vaccination patterns consistent with use of an alternative schedule. Children who by 9 months of age had at least 3 vaccination visits recorded in the statewide mandatory immunization information system after 41 days of age were classified as either attempting to conform to the Centers for Disease Control and Prevention published recommended vaccination schedule or an alternative schedule. The number of vaccination visits and up-to-date status at age 9 months were compared between groups. Of the 222 628 children studied, the proportion of children following an alternative schedule was 25%. These children were significantly less likely to be up-to-date at age 9 months (15%) compared with those conforming to the routine schedule (90%, P < .05). Children following an alternative schedule on average had about 2 extra vaccine visits compared with children following a routine schedule (P < .05). Almost 1 in 4 children in this study appear to be intentionally deviating from the routine schedule. Intentional deviation leads to poor vaccination coverage leaving children vulnerable to infection and increasing the potential for vaccine-preventable disease outbreaks. Copyright © 2015 Elsevier Inc. All rights reserved.

Immunogenicity of 23-Valent Pneumococcal Vaccine in Children with Systemic Lupus Erythematosus.

PubMed

Alyasin, Soheila; Adab, Marzieh; Hosseinpour, Asieh; Amin, Reza; Babaei, Maryam

2016-09-01

Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease which is characterized by B-cell abnormality and auto-antibody generation. Since bacterial infections are the most important causes of mortality in these patients, pneumococcal vaccination is recommended for children with SLE. To investigate humoral immunity and specific-antibody formation in response to a 23-valent polysaccharide pneumococcal vaccination in SLE children and asthmatic control group. The case and control groups consisted of 30 children with the mean age of 13 years who were matched by sex and age. Anti-pneumococcal antibody titers were determined using Enzyme-Linked Immunosorbent Assay (ELISA) before the vaccination with the 23-valent pneumococcal vaccine and 3 weeks later in both groups. Also the correlation between anti-pneumococcal antibody titer and different factors including age, sex, lupus activity, disease duration, medications, history of recurrent infections, and laboratory data were investigated. Both groups showed significant increases in anti-pneumococcal antibody level after vaccination (p≤0.001). The increase in antibody level were almost the same in both groups (p≥0.05) such that 77.7% of SLE children and 86.2% of control children showed at least 2-fold increase in anti-pneumococcal antibody titer following immunization. Significant correlations were seen between the level of post-immunization anti-pneumococcal antibody with the age of children with SLE (p=0.02) and their age of disease onset (p=0.02). It is concluded that pneumococcal vaccination is generally immunogenic in children with SLE. However, a small group of patients show impaired response to the vaccine.

Protein carriers of conjugate vaccines

PubMed Central

Pichichero, Michael E

2013-01-01

The immunogenicity of polysaccharides as human vaccines was enhanced by coupling to protein carriers. Conjugation transformed the T cell-independent polysaccharide vaccines of the past to T cell-dependent antigenic vaccines that were much more immunogenic and launched a renaissance in vaccinology. This review discusses the conjugate vaccines for prevention of infections caused by Hemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis. Specifically, the characteristics of the proteins used in the construction of the vaccines including CRM, tetanus toxoid, diphtheria toxoid, Neisseria meningitidis outer membrane complex, and Hemophilus influenzae protein D are discussed. The studies that established differences among and key features of conjugate vaccines including immunologic memory induction, reduction of nasopharyngeal colonization and herd immunity, and antibody avidity and avidity maturation are presented. Studies of dose, schedule, response to boosters, of single protein carriers with single and multiple polysaccharides, of multiple protein carriers with multiple polysaccharides and conjugate vaccines administered concurrently with other vaccines are discussed along with undesirable consequences of conjugate vaccines. The clear benefits of conjugate vaccines in improving the protective responses of the immature immune systems of young infants and the senescent immune systems of the elderly have been made clear and opened the way to development of additional vaccines using this technology for future vaccine products. PMID:23955057

Examining dog owners' beliefs regarding rabies vaccination during government-funded vaccine clinics in Grenada to improve vaccine coverage rates.

PubMed

Thomas, D; Delgado, A; Louison, B; Lefrancois, T; Shaw, J

2013-07-01

Vaccination of domestic pets is an important component of rabies control and prevention in countries where the disease is maintained in a wildlife reservoir. In Grenada, vaccine coverage rates were low, despite extensive public education and advertising of government-sponsored vaccine clinics where rabies vaccine is administered to animals at no cost to animal owners. Information was needed on reasons for decreased dog owner participation in government-funded rabies vaccination clinics. A total of 120 dog owners from 6 different parishes were asked to complete a questionnaire assessing their currently held beliefs about rabies vaccination and perception of the risk posed by rabies. Over 70% of respondents believed that problems in the organization and management of clinic sites could allow for fighting between dogs or disease spread among dogs, while 35% of owners did not believe that they had the ability or adequate help to bring their dogs to the clinic sites. Recommendations for improving vaccine coverage rates included: improved scheduling of clinic sites and dates; increased biosecurity at clinic locations; focused advertising on the availability of home visits, particularly for aggressive dogs or dogs with visible skin-related diseases such as mange; and the recruitment of community volunteers to assist with bringing dogs to the clinic sites. Copyright © 2013. Published by Elsevier B.V.

Application of “Systems Vaccinology” to Evaluate Inflammation and Reactogenicity of Adjuvanted Preventative Vaccines

PubMed Central

Lewis, David J. M.; Lythgoe, Mark P.

2015-01-01

Advances in “omics” technology (transcriptomics, proteomics, metabolomics, genomics/epigenomics, etc.) allied with statistical and bioinformatics tools are providing insights into basic mechanisms of vaccine and adjuvant efficacy or inflammation/reactogenicity. Predictive biomarkers of relatively frequent inflammatory reactogenicity may be identified in systems vaccinology studies involving tens or hundreds of participants and used to screen new vaccines and adjuvants in in vitro, ex vivo, animal, or human models. The identification of rare events (such as those observed with initial rotavirus vaccine or suspected autoimmune complications) will require interrogation of large data sets and population-based research before application of systems vaccinology. The Innovative Medicine Initiative funded public-private project BIOVACSAFE is an initial attempt to systematically identify biomarkers of relatively common inflammatory events after adjuvanted immunization using human, animal, and population-based models. Discriminatory profiles or biomarkers are being identified, which require validation in large trials involving thousands of participants before they can be generalized. Ultimately, it is to be hoped that the knowledge gained from such initiatives will provide tools to the industry, academia, and regulators to select optimal noninflammatory but immunogenic and effective vaccine adjuvant combinations, thereby shortening product development cycles and identifying unsuitable vaccine candidates that would fail in expensive late stage development or postmarketing. PMID:26380327

Vaccine hesitancy and healthcare providers.

PubMed

Paterson, Pauline; Meurice, François; Stanberry, Lawrence R; Glismann, Steffen; Rosenthal, Susan L; Larson, Heidi J

2016-12-20

While most people vaccinate according to the recommended schedule, this success is challenged by individuals and groups who delay or refuse vaccines. The aim of this article is to review studies on vaccine hesitancy among healthcare providers (HCPs), and the influences of their own vaccine confidence and vaccination behaviour on their vaccination recommendations to others. The search strategy was developed in Medline and then adapted across several multidisciplinary mainstream databases including Embase Classic & Embase, and PschInfo. All foreign language articles were included if the abstract was available in English. A total of 185 articles were included in the literature review. 66% studied the vaccine hesitancy among HCPs, 17% analysed concerns, attitudes and/or behaviour of HCPs towards vaccinating others, and 9% were about evaluating intervention(s). Overall, knowledge about particular vaccines, their efficacy and safety, helped to build HCPs own confidence in vaccines and their willingness to recommend vaccines to others. The importance of societal endorsement and support from colleagues was also reported. In the face of emerging vaccine hesitancy, HCPs still remain the most trusted advisor and influencer of vaccination decisions. The capacity and confidence of HCPs, though, are stretched as they are faced with time constraints, increased workload and limited resources, and often have inadequate information or training support to address parents' questions. Overall, HCPs need more support to manage the quickly evolving vaccine environment as well as changing public, especially those who are reluctant or refuse vaccination. Some recommended strategies included strengthening trust between HCPs, health authorities and policymakers, through more shared involvement in the establishment of vaccine recommendations. Copyright © 2016. Published by Elsevier Ltd.

Modular vaccine packaging increases packing efficiency

PubMed Central

Norman, Bryan A.; Rajgopal, Jayant; Lim, Jung; Gorham, Katrin; Haidari, Leila; Brown, Shawn T.; Lee, Bruce Y.

2015-01-01

Background Within a typical vaccine supply chain, vaccines are packaged into individual cylindrical vials (each containing one or more doses) that are bundled together in rectangular “inner packs” for transport via even larger groupings such as cold boxes and vaccine carriers. The variability of vaccine inner pack and vial size may hinder efficient vaccine distribution because it constrains packing of cold boxes and vaccine carriers to quantities that are often inappropriate or suboptimal in the context of country-specific vaccination guidelines. Methods We developed in Microsoft Excel (Microsoft Corp., Redmond, WA) a spreadsheet model that evaluated the impact of different packing schemes for the Benin routine regimen plus the introduction of the Rotarix vaccine. Specifically, we used the model to compare the current packing scheme to that of a proposed modular packing scheme. Results Conventional packing of a Dometic RCW25 that aims to maximize fully-immunized children (FICs) results in 123 FICs and a packing efficiency of 81.93% compared to a maximum of 155 FICs and 94.1% efficiency for an alternative modular packaging system. Conclusions Our analysis suggests that modular packaging systems could offer significant advantages over conventional vaccine packaging systems with respect to space efficiency and potential FICs, when they are stored in standard vaccine carrying devices. This allows for more vaccines to be stored within the same volume while also simplifying the procedures used by field workers to pack storage devices. Ultimately, modular packaging systems could be a simple way to help increase vaccine coverage worldwide. PMID:25957666

Nanodelivery Systems as New Tools for Immunostimulant or Vaccine Administration: Targeting the Fish Immune System

PubMed Central

Ji, Jie; Torrealba, Debora; Ruyra, Àngels; Roher, Nerea

2015-01-01

Fish disease treatments have progressed significantly over the last few years and have moved from the massive use of antibiotics to the development of vaccines mainly based on inactivated bacteria. Today, the incorporation of immunostimulants and antigens into nanomaterials provide us with new tools to enhance the performance of immunostimulation. Nanoparticles are dispersions or solid particles designed with specific physical properties (size, surface charge, or loading capacity), which allow controlled delivery and therefore improved targeting and stimulation of the immune system. The use of these nanodelivery platforms in fish is in the initial steps of development. Here we review the advances in the application of nanoparticles to fish disease prevention including: the type of biomaterial, the type of immunostimulant or vaccine loaded into the nanoparticles, and how they target the fish immune system. PMID:26492276

Immunomodulatory properties of vitamins, flavonoids and plant oils and their potential as vaccine adjuvants and delivery systems.

PubMed

Vajdy, Michael

2011-11-01

During the past century, vaccinologists have attempted to mimic pathogens in their immune-enhancing capacity. This led to the development of life-saving vaccines based on live attenuated viruses, bacteria and toxoids. Hence, intense research in vaccine adjuvant discovery has focused on toll like receptors, mutant toxins and viral and bacterial vectors. Nutritive components such as vitamins and select polyphenols also possess immunomodulating properties without the potential toxic and adverse side effects of agents that mimic danger signals. This review pertains to immunomodulatory properties of nutritive components, that is vitamins A, C, D, E, flavonoids and plant oils, as potential vaccine adjuvants and delivery systems, covering Pubmed publication searches from 1980 through 2011. This relatively unexplored field of the potential of nutritive components as vaccine adjuvants holds great promise to promote the development of effective and above all safe vaccines. Hence the future focus should be placed on enhancing their efficacy, mainly through novel approaches in designing structural derivatives, formulations, delivery systems and routes of administration. As safety has been the major issue in development of novel vaccines, this new approach will probably result in new discoveries in designing safe and effective vaccines.

User evaluation of photovoltaic-powered vaccine refrigerator/freezer systems

NASA Technical Reports Server (NTRS)

Ratajczak, Anthony F.

1987-01-01

The NASA Lewis Research Center has concluded a project to develop and field test photovoltaic-powered refrigerator/freezers for vaccine storage in remote areas of developing countries. As a conclusion to this project, questionnaires were sent to the in-country administrators for each test site probing user acceptance of the systems and attitudes regarding procurement of additional systems. Responses indicate that the systems had a positive effect on the local communities, that they made a positive impression on the local health authorities, and that system cost and scarcity of funds are the major barriers to procurements of additional systems.

User evaluation of photovoltaic-powered vaccine refrigerator/freezer systems

NASA Astrophysics Data System (ADS)

Ratajczak, Anthony F.

1987-03-01

The NASA Lewis Research Center has concluded a project to develop and field test photovoltaic-powered refrigerator/freezers for vaccine storage in remote areas of developing countries. As a conclusion to this project, questionnaires were sent to the in-country administrators for each test site probing user acceptance of the systems and attitudes regarding procurement of additional systems. Responses indicate that the systems had a positive effect on the local communities, that they made a positive impression on the local health authorities, and that system cost and scarcity of funds are the major barriers to procurements of additional systems.

Accuracy of parent-reported measles-containing vaccination status of children with measles.

PubMed

Liu, G; Liao, Z; Xu, X; Liang, Y; Xiong, Y; Ni, J

2017-03-01

The validity of parent-reported measles-containing vaccination history in children with measles has not been assessed. This study evaluated the accuracy of parental recall of measles-containing vaccination histories in Shenzhen, China. A retrospective study was performed to compare the data from the electronic records with parental recall. The electronic records were regarded as accurate data about the children's measles-containing vaccination status. We collected data from the National Notifiable Diseases Surveillance System and the Immunization Program Information Management System in Shenzhen city, China. Between 2009 and 2014, there were 163 children with measles who had electronic vaccination records; the vaccination status of these cases was reported by the parents in the field epidemiological investigation. We validated parental recall with electronic records. The agreement between parental recall and electronic records was 78.7%. The kappa value was 0.57. The parent-reported measles-containing vaccination rate was higher than the electronic record (48.5% vs 41.7%, χ 2  = 53.64, P < 0.001). The true positive rate for parental recall was 82.4%, and the true negative rate was 75.8%. The positive predictive value was 70.9%, and the negative predictive value was 76.6%. In children with measles, parental recall slightly overestimated the measles vaccination rate, and the vaccination status recalled by parents was in moderate agreement with the electronic record. Copyright © 2016 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

Rice-based mucosal vaccine as a global strategy for cold-chain- and needle-free vaccination

PubMed Central

Nochi, Tomonori; Takagi, Hidenori; Yuki, Yoshikazu; Yang, Lijun; Masumura, Takehiro; Mejima, Mio; Nakanishi, Ushio; Matsumura, Akiko; Uozumi, Akihiro; Hiroi, Takachika; Morita, Shigeto; Tanaka, Kunisuke; Takaiwa, Fumio; Kiyono, Hiroshi

2007-01-01

Capable of inducing antigen-specific immune responses in both systemic and mucosal compartments without the use of syringe and needle, mucosal vaccination is considered ideal for the global control of infectious diseases. In this study, we developed a rice-based oral vaccine expressing cholera toxin B subunit (CTB) under the control of the endosperm-specific expression promoter 2.3-kb glutelin GluB-1 with codon usage optimization for expression in rice seed. An average of 30 μg of CTB per seed was stored in the protein bodies, which are storage organelles in rice. When mucosally fed, rice seeds expressing CTB were taken up by the M cells covering the Peyer's patches and induced CTB-specific serum IgG and mucosal IgA antibodies with neutralizing activity. When expressed in rice, CTB was protected from pepsin digestion in vitro. Rice-expressed CTB also remained stable and thus maintained immunogenicity at room temperature for >1.5 years, meaning that antigen-specific mucosal immune responses were induced at much lower doses than were necessary with purified recombinant CTB. Because they require neither refrigeration (cold-chain management) nor a needle, these rice-based mucosal vaccines offer a highly practical and cost-effective strategy for orally vaccinating large populations against mucosal infections, including those that may result from an act of bioterrorism. PMID:17573530

Vaccines Cold Chain Monitoring: A Cross Sectional Study at Three District In Indonesia

NASA Astrophysics Data System (ADS)

Saraswati, L. D.; Ginandjar, P.; Budiyono; Martini; Udiyono, A.; Kairul

2018-02-01

Vaccine cold chain is a procedure that is used to keep vaccines at a certain temperature. The aim was to describe the vaccine cold chain management of basic immunization program in health centers district. The study design descriptive observational. The samples was Health Centers (HCs); 12 HCs in Sarolangun Jambi Province, 16 HCs in Brebes Central Java Province, and 24 HCs in Temanggung Central Java Provice. Basic immunization vaccines were BCG, DPT-HB-HIB, Polio, and Measles. The results showed proportion of officers graduated from college in Sorolangun, Brebes, and Temanggung were 66.7%, 81.3%, and 52.0% respectively. Proportion of HC that did not have thermometer and fridge freeze was mostly found in Temanggung (52%) and in Sorolangun (91.7%). The heat-sensitive vaccines arranged near the evaporator mostly found in Temanggung (88%), while freeze-sensitive vaccines prepared away of the evaporator mostly in Brebes (100%). Freezer temperature recording chart is not available mostly found in Sorolangun and Brebes (50%), In Sorolangun 41.7% of the officers monitoring 2 times a day and mostly (91.7%) the refrigerator thermostat tape was not isolated. The officers did not perform daily maintenance (50%), weekly (66.7%), and montly (33.3%) mostly found in Sorolangun. From this study we can conclude there is no vaccine immunization program management in Sarolangun, Brebes, and Temanggung that managed according to Ministry of Health Regulations number 42/2013 on the Implementation of immunization. Improvement oversight, control over management of vaccine and management personal, also managing the temperature of the vaccine were recommended.

New South Wales annual vaccine-preventable disease report, 2012

PubMed Central

Spokes, Paula; Gilmour, Robin

2014-01-01

We aim to describe the epidemiology of selected vaccine-preventable diseases in New South Wales (NSW) for 2012. Data from the NSW Notifiable Conditions Information Management System were analysed by: local health district of residence, age, Aboriginality, vaccination status and organism, where available. Risk factor and vaccination status data were collected by public health units for cases following notification under the NSW Public Health Act 2010. The largest outbreak of measles since 1998 was reported in 2012. Pacific Islander and Aboriginal people were at higher risk as were infants less than 12 months of age. Notifications of invasive pneumococcal disease (IPD) in children less than five years declined; however, the overall number of notifications for IPD increased. Mumps case notifications were also elevated. There were no Haemophilus influenzae type b case notifications in children less than five years of age for the first time since the vaccine was introduced. Invasive meningococcal disease case notifications were at their lowest rates since case notification began in 1991. Case notification rates for other selected vaccine-preventable diseases remained stable. Vaccine-preventable disease control is continually strengthening in NSW with notable successes in invasive bacterial infections. However, strengthening measles immunization in Pacific Islander and Aboriginal communities remains essential to maintain measles elimination. PMID:25077033

New South Wales annual vaccine-preventable disease report, 2012.

PubMed

Rosewell, Alexander; Spokes, Paula; Gilmour, Robin

2014-01-01

We aim to describe the epidemiology of selected vaccine-preventable diseases in New South Wales (NSW) for 2012. Data from the NSW Notifiable Conditions Information Management System were analysed by: local health district of residence, age, Aboriginality, vaccination status and organism, where available. Risk factor and vaccination status data were collected by public health units for cases following notification under the NSW Public Health Act 2010. The largest outbreak of measles since 1998 was reported in 2012. Pacific Islander and Aboriginal people were at higher risk as were infants less than 12 months of age. Notifications of invasive pneumococcal disease (IPD) in children less than five years declined; however, the overall number of notifications for IPD increased. Mumps case notifications were also elevated. There were no Haemophilus influenzae type b case notifications in children less than five years of age for the first time since the vaccine was introduced. Invasive meningococcal disease case notifications were at their lowest rates since case notification began in 1991. Case notification rates for other selected vaccine-preventable diseases remained stable. Vaccine-preventable disease control is continually strengthening in NSW with notable successes in invasive bacterial infections. However, strengthening measles immunization in Pacific Islander and Aboriginal communities remains essential to maintain measles elimination.

Vaccine supply chains need to be better funded and strengthened, or lives will be at risk.

PubMed

Kaufmann, Judith R; Miller, Roger; Cheyne, James

2011-06-01

In the next decade, at least twelve additional vaccines that target such diseases as typhoid, malaria, and dengue will become available to lower- and middle-income countries. These vaccines must travel along what are called supply chains, which include all personnel, systems, equipment, and activities involved in ensuring that vaccines are effectively delivered from the point of production to the people who need them. But for various reasons, supply chains are already strained in many developing countries, and the potential inability to distribute new vaccines will place lives at risk. Among the many steps needed to strengthen the global vaccine supply chain, we suggest that the international community pursue improved coordination between organizations that donate and ship vaccines and the host-country officials who receive and distribute the vaccines, as well as better training for supply-chain managers.

Maternal vaccination: moving the science forward

PubMed Central

Faucette, Azure N.; Unger, Benjamin L.; Gonik, Bernard; Chen, Kang

2015-01-01

BACKGROUND Infections remain one of the leading causes of morbidity in pregnant women and newborns, with vaccine-preventable infections contributing significantly to the burden of disease. In the past decade, maternal vaccination has emerged as a promising public health strategy to prevent and combat maternal, fetal and neonatal infections. Despite a number of universally recommended maternal vaccines, the development and evaluation of safe and effective maternal vaccines and their wide acceptance are hampered by the lack of thorough understanding of the efficacy and safety in the pregnant women and the offspring. METHODS An outline was synthesized based on the current status and major gaps in the knowledge of maternal vaccination. A systematic literature search in PUBMED was undertaken using the key words in each section title of the outline to retrieve articles relevant to pregnancy. Articles cited were selected based on relevance and quality. On the basis of the reviewed information, a perspective on the future directions of maternal vaccination research was formulated. RESULTS Maternal vaccination can generate active immune protection in the mother and elicit systemic immunoglobulin G (IgG) and mucosal IgG, IgA and IgM responses to confer neonatal protection. The maternal immune system undergoes significant modulation during pregnancy, which influences responsiveness to vaccines. Significant gaps exist in our knowledge of the efficacy and safety of maternal vaccines, and no maternal vaccines against a large number of old and emerging pathogens are available. Public acceptance of maternal vaccination has been low. CONCLUSIONS To tackle the scientific challenges of maternal vaccination and to provide the public with informed vaccination choices, scientists and clinicians in different disciplines must work closely and have a mechanistic understanding of the systemic, reproductive and mammary mucosal immune responses to vaccines. The use of animal models should be

Utilizing population variation, vaccination, and systems biology to study human immunology

PubMed Central

Tsang, John S.

2016-01-01

The move toward precision medicine has highlighted the importance of understanding biological variability within and across individuals in the human population. In particular, given the prevalent involvement of the immune system in diverse pathologies, an important question is how much and what information about the state of the immune system is required to enable accurate prediction of future health and response to medical interventions. Towards addressing this question, recent studies using vaccination as a model perturbation and systems-biology approaches are beginning to provide a glimpse of how natural population variation together with multiplexed, high-throughput measurement and computational analysis can be used to uncover predictors of immune response quality in humans. Here I discuss recent developments in this emerging field, with emphasis on baseline correlates of vaccination responses, sources of immune-state variability, as well as relevant features of study design, data generation, and computational analysis. PMID:26187853

Canadian Adverse Events Following Immunization Surveillance System (CAEFISS): Annual report for vaccines administered in 2012

PubMed Central

Law, BJ; Laflèche, J; Ahmadipour, N; Anyoti, H

2014-01-01

Background To describe the adverse event following immunization (AEFI) reporting profile for vaccines administered in Canada during 2012 and surveillance trends relative to reports for vaccines administered from 2005 through 2011. Methods Analysis of data based on AEFI reports received by the Public Health Agency of Canada by April 30, 2013, for vaccines marketed in Canada and administered from January 1, 2005, through December 31, 2012. Results The AEFI reporting rate was 10.1 per 100,000 population in Canada for vaccines administered in 2012 and was inversely proportional to age. There was a trend of declining rates from 2005 (14.8) to 2012 overall and by age group. The vast majority of reports (94%−95%) were non-serious involving reactions at or near the vaccination site, rash and febrile events. Conclusion Canada has a strong pharmacovigilance system for vaccines with one of the highest AEFI reporting rates in developed countries. Vaccines marketed in Canada have a very good safety profile. This report enables comparisons across jurisdictions in Canada and globally. PMID:29769908

Bringing influenza vaccines into the 21st century

PubMed Central

Settembre, Ethan C; Dormitzer, Philip R; Rappuoli, Rino

2014-01-01

The recent H7N9 influenza outbreak in China highlights the need for influenza vaccine production systems that are robust and can quickly generate substantial quantities of vaccines that target new strains for pandemic and seasonal immunization. Although the influenza vaccine system, a public-private partnership, has been effective in providing vaccines, there are areas for improvement. Technological advances such as mammalian cell culture production and synthetic vaccine seeds provide a means to increase the speed and accuracy of targeting new influenza strains with mass-produced vaccines by dispensing with the need for egg isolation, adaptation, and reassortment of vaccine viruses. New influenza potency assays that no longer require the time-consuming step of generating sheep antisera could further speed vaccine release. Adjuvants that increase the breadth of the elicited immune response and allow dose sparing provide an additional means to increase the number of available vaccine doses. Together these technologies can improve the influenza vaccination system in the near term. In the longer term, disruptive technologies, such as RNA-based flu vaccines and ‘universal’ flu vaccines, offer a promise of a dramatically improved influenza vaccine system. PMID:24378716

Bringing influenza vaccines into the 21st century.

PubMed

Settembre, Ethan C; Dormitzer, Philip R; Rappuoli, Rino

2014-01-01

The recent H7N9 influenza outbreak in China highlights the need for influenza vaccine production systems that are robust and can quickly generate substantial quantities of vaccines that target new strains for pandemic and seasonal immunization. Although the influenza vaccine system, a public-private partnership, has been effective in providing vaccines, there are areas for improvement. Technological advances such as mammalian cell culture production and synthetic vaccine seeds provide a means to increase the speed and accuracy of targeting new influenza strains with mass-produced vaccines by dispensing with the need for egg isolation, adaptation, and reassortment of vaccine viruses. New influenza potency assays that no longer require the time-consuming step of generating sheep antisera could further speed vaccine release. Adjuvants that increase the breadth of the elicited immune response and allow dose sparing provide an additional means to increase the number of available vaccine doses. Together these technologies can improve the influenza vaccination system in the near term. In the longer term, disruptive technologies, such as RNA-based flu vaccines and 'universal' flu vaccines, offer a promise of a dramatically improved influenza vaccine system.

Acellular vaccines for preventing whooping cough in children.

PubMed

Zhang, Linjie; Prietsch, Sílvio Om; Axelsson, Inge; Halperin, Scott A

2011-01-19

Routine use of whole-cell pertussis vaccines was suspended in some countries in the 1970s/1980s because of concerns about adverse effects. There was a resurgence of whooping cough. Acellular pertussis vaccines (containing purified or recombinant Bordetella pertussis antigens) were developed in the hope that they would be as effective but less reactogenic than the whole-cell vaccines. To assess the efficacy and safety of acellular pertussis vaccines in children. We searched the Cochrane Register of Controlled Trials (CENTRAL) (The Cochrane Library 2009, issue 2) which contains the Acute Respiratory Infections Group's Specialised Register; MEDLINE (1950 to April week 2 2009) and EMBASE (1974 to April 2009). Double-blind randomised efficacy and safety trials of acellular pertussis vaccines in children up to six years old, with active follow-up of participants and laboratory verification of pertussis cases. Two review authors independently performed data extraction and study quality assessment. Differences in trial design precluded pooling of the efficacy data. The safety data from individual trials were pooled using the Cochrane statistical package Review Manager 5. Six efficacy trials and 52 safety trials were included. The efficacy of multi-component (≥ 3) vaccines varied from 84% to 85% in preventing typical whooping cough, and from 71% to 78% in preventing mild pertussis disease. In contrast, the efficacy of one- and two-component vaccines varied from 59% to 75% against typical whooping cough, and from 13% to 54% against mild pertussis disease. Multi-component acellular vaccines is more effective than low-efficacy whole-cell vaccines, but may be less effective than the highest-efficacy whole-cell vaccines. Most systemic and local adverse events were significantly less common with acellular than with whole-cell pertussis vaccines for the primary series as well as for the booster dose. Multi-component acellular pertussis vaccines are effective, and show less

Impact of piglet oral vaccination against tuberculosis in endemic free-ranging wild boar populations.

PubMed

Díez-Delgado, Iratxe; Sevilla, Iker A; Romero, Beatriz; Tanner, Eleanor; Barasona, Jose A; White, Andrew R; Lurz, Peter W W; Boots, Mike; de la Fuente, José; Dominguez, Lucas; Vicente, Joaquin; Garrido, Joseba M; Juste, Ramón A; Aranaz, Alicia; Gortazar, Christian

2018-07-01

The Eurasian wild boar (Sus scrofa) is the main wild reservoir of the Mycobacterium tuberculosis complex in Mediterranean woodlands and a key risk factor for cattle tuberculosis (TB) breakdowns. Wild boar vaccination therefore has the potential to be a valuable tool for TB control. We tested two orally delivered vaccines, heat-inactivated Mycobacterium bovis (IV) and BCG, in four sites (two per vaccine type: one Managed and one Natural or unmanaged) during four years. TB was also monitored in 15 unvaccinated sites (spatial control), as well as in all sites from one year prior to intervention (temporal control). The rationale is that by vaccinating 2-6 month old wild boar piglets we can reduce disease at the population level during the study period. This is achievable due to the fast turnover of wild boar populations. Vaccine baits were deployed using selective piglet feeders and this method proved highly successful with uptake rates of 50 to 74% in Natural sites and 89 to 92% in Managed sites. This is relevant for the potential delivery of vaccines to control other diseases, too. Local wild boar TB prevalence at the beginning of the study was already high ranging from 50 to 100%. TB prevalence increased in unvaccinated sites (6%), while a significant decline occurred in the Managed IV site (34%). Changes recorded in the remaining sites were not significant. The short-term impact of vaccination observed in the field was complemented by mathematical modelling, representative of the field system, which examined the long-term impact and showed that vaccination of piglets reduced prevalence and increased abundance at the population level. We conclude that IV could become part of integrated TB control schemes, although its application must be tailored for each specific site. Copyright © 2018 Elsevier B.V. All rights reserved.

Physicians', Nurses', and Medical Assistants' Perceptions of the Human Papillomavirus Vaccine in a Large Integrated Health Care System.

PubMed

Mills, Jordan; Van Winkle, Patrick; Shen, Macy; Hong, Christina; Hudson, Sharon

2016-01-01

Vaccination against the human papillomavirus (HPV) decreases risks of cancer and genital warts and the need for gynecologic procedures, yet nationwide vaccination rates are low. Previous surveys exploring this phenomenon have not included input from nurses and medical assistants, who play integral roles in HPV vaccine delivery. To understand perceptions of HPV vaccine delivery among physicians, nurses, and medical assistants in a large integrated health care system in Southern California. Online surveys were sent to 13 nurse administrators and 75 physicians. Physicians were instructed to forward the survey to nurses and medical assistants with whom they work. A total of 76 surveys were completed, consisting of 52 physicians, 16 clinical nurses and medical assistants, and 8 nurse administrators. Physicians' perceptions of vaccine safety or strength of recommendation did not differ by specialty department. Physicians reportedly perceived the HPV vaccine as safer than did clinical nurses and medical assistants (p < 0.001), who indicated they wanted more education on the safety and efficacy of the vaccine before being comfortable strongly recommending it. Respondents advised that all clinicians could improve in their roles as HPV vaccine advocates through patient counseling and providing informational literature and that workflow standardization was needed to minimize missed vaccination opportunities. Physicians reportedly perceive the HPV vaccine as safer compared with nurses and medical assistants. Both groups think that more education of nonphysician staff is needed. Having proper systems in place is also vital to improving vaccination compliance.

Physicians’, Nurses’, and Medical Assistants’ Perceptions of the Human Papillomavirus Vaccine in a Large Integrated Health Care System

PubMed Central

Mills, Jordan; Van Winkle, Patrick; Shen, Macy; Hong, Christina; Hudson, Sharon

2016-01-01

Context Vaccination against the human papillomavirus (HPV) decreases risks of cancer and genital warts and the need for gynecologic procedures, yet nationwide vaccination rates are low. Previous surveys exploring this phenomenon have not included input from nurses and medical assistants, who play integral roles in HPV vaccine delivery. Objective To understand perceptions of HPV vaccine delivery among physicians, nurses, and medical assistants in a large integrated health care system in Southern California. Design Online surveys were sent to 13 nurse administrators and 75 physicians. Physicians were instructed to forward the survey to nurses and medical assistants with whom they work. Results A total of 76 surveys were completed, consisting of 52 physicians, 16 clinical nurses and medical assistants, and 8 nurse administrators. Physicians’ perceptions of vaccine safety or strength of recommendation did not differ by specialty department. Physicians reportedly perceived the HPV vaccine as safer than did clinical nurses and medical assistants (p < 0.001), who indicated they wanted more education on the safety and efficacy of the vaccine before being comfortable strongly recommending it. Respondents advised that all clinicians could improve in their roles as HPV vaccine advocates through patient counseling and providing informational literature and that workflow standardization was needed to minimize missed vaccination opportunities. Conclusion Physicians reportedly perceive the HPV vaccine as safer compared with nurses and medical assistants. Both groups think that more education of nonphysician staff is needed. Having proper systems in place is also vital to improving vaccination compliance. PMID:27643974

Specific IgE and IgG to gelatin in children with systemic cutaneous reactions to Japanese encephalitis vaccines.

PubMed

Sakaguchi, M; Miyazawa, H; Inouye, S

2001-06-01

Systemic allergic reactions to Japanese encephalitis (JE) vaccine that include urticaria, angioedema, and rash have been reported. In Japan, children who suffered from allergic immediate-type reactions to JE vaccine had antigelatin IgE in their sera. However, the immunologic mechanism of allergic nonimmediate-type reactions that consist of cutaneous signs appearing several hours or more after JE vaccination has not been defined. Serum samples were taken from 28 children who showed allergic nonimmediate-type cutaneous reactions to JE vaccine. Furthermore, serum samples were taken from 10 children who showed allergic immediate-type reactions with cutaneous signs and/or respiratory symptoms to JE vaccine. We have defined an immediate-type reaction as one occurring within 1 h after vaccination. Of 10 children who showed immediate-type reactions, all had antigelatin IgE and IgG. Of 28 children who showed systemic nonimmediate-type reactions, one had antigelatin IgE and nine (32%) had antigelatin IgG. The child who had antigelatin IgE showed urticaria 2 h after JE vaccination. These results suggest that some children who showed allergic nonimmediate-type reactions to JE vaccine were sensitized to gelatin.

Vaccines against biologic agents: uses and developments.

PubMed

Ales, Noel C; Katial, Rohit K

2004-03-01

Although the Geneva protocol that prohibits the use of chemical and biologic weapons was ratified in 1925, many countries failed to accept this protocol: others stipulated retaliation, and some, like the United States, did not ratify the protocol for decades. This delay allowed the continued development of chemical and biologic agents. Members of the health care community are responsible for determining the best way to protect society from the potentially devastating effects of these biologic agents. Ideally,these diseases would be prevented from ever developing into systemic illnesses. In the past, vaccination has been a successful means of eradicating disease. Vaccines remain a hopeful therapy for the future, but time is short,and there are many obstacles.Information regarding bioterrorism agents and their treatments comes mainly from dated data or from in vitro or animal studies that may not apply to human treatment and disease. Additionally, the current threat of bioterrorism does not allow enough time for accurate, well-designed,controlled studies in humans before the release of investigational vaccines. Furthermore, some human studies would not be safe or ethical. Finally,many members of society suffer from illnesses that would put them at high risk to receive prophylactic vaccination. It is therefore naive to believe that vaccines would be the ultimate protection from these agents. In addition to vaccine development, there must be concurrent investigations into disease management and treatment. Even in instances in which vaccination is known to be an effective means of disease protection. biologic agents may be presented in a manner that renders vaccines ineffective. Virulent strains of organisms may be used, more than one organism may be used in tandem to increase virulence, and strains may be selected for antibiotic and vaccine resistance. Genetically engineered strains may use virulence factors other than those targeted in vaccines, and high

Post-licensure safety monitoring of quadrivalent human papillomavirus vaccine in the Vaccine Adverse Event Reporting System (VAERS), 2009-2015.

PubMed

Arana, Jorge E; Harrington, Theresa; Cano, Maria; Lewis, Paige; Mba-Jonas, Adamma; Rongxia, Li; Stewart, Brock; Markowitz, Lauri E; Shimabukuro, Tom T

2018-03-20

The Food and Drug Administration (FDA) approved quadrivalent human papillomavirus vaccine (4vHPV) for use in females and males aged 9-26 years, since 2006 and 2009 respectively. We characterized reports to the Vaccine Adverse Event Reporting System (VAERS), a US spontaneous reporting system, in females and males who received 4vHPV vaccination. We searched VAERS for US reports of adverse events (AEs) following 4vHPV from January 2009 through December 2015. Signs and symptoms were coded using Medical Dictionary for Regulatory Activities (MedDRA). We calculated reporting rates and conducted empirical Bayesian data mining to identify disproportional reports. Clinicians reviewed available information, including medical records, and reports of selected pre-specified conditions. VAERS received 19,760 reports following 4vHPV; 60.2% in females, 17.2% in males, and in 22.6% sex was missing. Overall, 94.2% of reports were non-serious; dizziness, syncope and injection site reactions were commonly reported in both males and females. Headache, fatigue and nausea were commonly reported serious AEs. More than 60 million 4vHPV doses were distributed during the study period. Crude AE reporting rates were 327 reports per million 4vHPV doses distributed for all reports, and 19 per million for serious reports. Among 29 verified reports of death, there was no pattern of clustering of deaths by diagnosis, co-morbidities, age, or interval from vaccination to death. No new or unexpected safety concerns or reporting patterns of 4vHPV with clinically important AEs were detected. Safety profile of 4vHPV is consistent with data from pre-licensure trials and postmarketing safety data. Published by Elsevier Ltd.

Autodisplay: Development of an Efficacious System for Surface Display of Antigenic Determinants in Salmonella Vaccine Strains

PubMed Central

Kramer, Uwe; Rizos, Konstantin; Apfel, Heiko; Autenrieth, Ingo B.; Lattemann, Claus T.

2003-01-01

To optimize antigen delivery by Salmonella vaccine strains, a system for surface display of antigenic determinants was established by using the autotransporter secretion pathway of gram-negative bacteria. A modular system for surface display allowed effective targeting of heterologous antigens or fragments thereof to the bacterial surface by the autotransporter domain of AIDA-I, the Escherichia coli adhesin involved in diffuse adherence. A major histocompatibility complex class II-restricted epitope, comprising amino acids 74 to 86 of the Yersinia enterocolitica heat shock protein Hsp60 (Hsp6074-86), was fused to the AIDA-I autotransporter domain, and the resulting fusion protein was expressed at high levels on the cell surface of E. coli and Salmonella enterica serovar Typhimurium. Colonization studies in mice vaccinated with Salmonella strains expressing AIDA-I fusion proteins demonstrated high genetic stability of the generated vaccine strain in vivo. Furthermore, a pronounced T-cell response against Yersinia Hsp6074-86 was induced in mice vaccinated with a Salmonella vaccine strain expressing the Hsp6074-86-AIDA-I fusion protein. This was shown by monitoring Yersinia Hsp60-stimulated IFN-γ secretion and proliferation of splenic T cells isolated from vaccinated mice. These results demonstrate that the surface display of antigenic determinants by the autotransporter pathway deserves special attention regarding the application in live attenuated Salmonella vaccine strains. PMID:12654812

Autodisplay: development of an efficacious system for surface display of antigenic determinants in Salmonella vaccine strains.

PubMed

Kramer, Uwe; Rizos, Konstantin; Apfel, Heiko; Autenrieth, Ingo B; Lattemann, Claus T

2003-04-01

To optimize antigen delivery by Salmonella vaccine strains, a system for surface display of antigenic determinants was established by using the autotransporter secretion pathway of gram-negative bacteria. A modular system for surface display allowed effective targeting of heterologous antigens or fragments thereof to the bacterial surface by the autotransporter domain of AIDA-I, the Escherichia coli adhesin involved in diffuse adherence. A major histocompatibility complex class II-restricted epitope, comprising amino acids 74 to 86 of the Yersinia enterocolitica heat shock protein Hsp60 (Hsp60(74-86)), was fused to the AIDA-I autotransporter domain, and the resulting fusion protein was expressed at high levels on the cell surface of E. coli and Salmonella enterica serovar Typhimurium. Colonization studies in mice vaccinated with Salmonella strains expressing AIDA-I fusion proteins demonstrated high genetic stability of the generated vaccine strain in vivo. Furthermore, a pronounced T-cell response against Yersinia Hsp60(74-86) was induced in mice vaccinated with a Salmonella vaccine strain expressing the Hsp60(74-86)-AIDA-I fusion protein. This was shown by monitoring Yersinia Hsp60-stimulated IFN-gamma secretion and proliferation of splenic T cells isolated from vaccinated mice. These results demonstrate that the surface display of antigenic determinants by the autotransporter pathway deserves special attention regarding the application in live attenuated Salmonella vaccine strains.

Vaccines in a hurry.

PubMed

Søborg, Christian; Mølbak, Kåre; Doherty, T Mark; Ulleryd, Peter; Brooks, Tim; Coenen, Claudine; van der Zeijst, Ben

2009-05-26

Preparing populations for health threats, including threats from new or re-emerging infectious diseases is recognised as an important public health priority. The development, production and application of emergency vaccinations are the important measures against such threats. Vaccines are cost-effective tools to prevent disease, and emergency vaccines may be the only means to prevent a true disaster for global society in the event of a new pandemic with potential to cause morbidity and mortality comparable to the Spanish flu, the polio epidemics in the 1950s, or the SARS outbreak in 2003 if its spread had not been contained in time. Given the early recognition of a new threat, and given the advances of biotechnology, vaccinology and information systems, it is not an unrealistic goal to have promising prototype vaccine candidates available in a short time span following the identification of a new infectious agent; this is based on the assumption that the emerging infection is followed by natural immunity. However, major bottlenecks for the deployment of emergency vaccine are lack of established systems for fast-track regulatory approval of such candidates and limited international vaccine production capacity. In the present discussion paper, we propose mechanisms to facilitate development of emergency vaccines in Europe by focusing on public-private scientific partnerships, fast-track approval of emergency vaccine by regulatory agencies and proposing incentives for emergency vaccine production in private vaccine companies.

[History of Smallpox Vaccination and of the Vaccine Supply in Hungary, up to 1890].

PubMed

Kiss, László

2015-01-01

One of the preconditions for the spread of vaccination against pox diseases was making vaccination available. The first vaccinations were carried out using original cowpox lymph sent by Jenner. For further vaccinations the vaccine was extracted from the blisters of those who had been successfully inoculated. In order to provide vaccine continuously six vaccine centres were set up in 1804 in the following cities: Pest, Buda, Kassa, Gyula, Pozsony and Zágráb (Croatia). Detailed information is available only about the centre in Pest which operated in Rókus Hospital under the leadership of the hospital director András Bossányi. Besides regular vaccination they also provided vaccine for the countryside. From 1824 the vaccine was relocated to the medical faculty of the university in Pest and Ferenc Gebhardt, an instructor of surgeons, became its head. The centre operated in the building of the medical faculty and vaccinations were given on Thursdays and Sundays. After the retirement of Gebhardt in 1860, the centre was taken over by the dermatologist Ferenc Poor for a short time, then by Ignác Semmelweis. From 1863 Gergely Patrubány was responsible for managing the centre. In 1874 the central vaccine institution moved to the Hospital for Poor Children in Pest where it was led first by Lázár Wittman, then by Géza Hainiss. In the 1880s private institutions appeared, the best known were Dani Pécsi's centre in Pest and Béla Intze's one in Tirgu Lapus (Romania). Between 1873 an 1889 András Kreichel ran a vaccine centre in Nálepkovo (Slovakia).

Vaccine preventable meningitis in Malaysia: epidemiology and management.

PubMed

McNeil, Hannah C; Jefferies, Johanna M C; Clarke, Stuart C

2015-06-01

Worldwide bacterial meningitis accounts for more than one million cases and 135,000 deaths annually. Profound, lasting neurological complications occur in 9-25% of cases. This review confirms the greatest risk from bacterial meningitis is in early life in Malaysia. Much of the disease burden can be avoided by immunization, particularly against Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae. Despite inclusion of the Hib vaccine in the National Immunisation Programme and the licensure of pneumococcal vaccines, these two species are the main contributors to bacterial meningitis in Malaysia, with Neisseria meningitidis and Mycobacterium tuberculosis, causing a smaller proportion of disease. The high Hib prevalence may partly be due to dated, small-scale studies limiting the understanding of the current epidemiological situation. This highlights the need for larger, better quality surveillance from Malaysia to evaluate the success of Hib immunization and to help guide immunization policy for vaccines against S. pneumoniae and N. meningitidis.

[The National Vaccine Injury Compensation Program in Japan].

PubMed

Ihara, Toshiaki

2011-09-01

Two vaccination systems have been employed in Japan, the routine vaccination and the voluntary vaccination. The National Vaccine Injury Compensation Program in Japan is no-fault system. Claims after the routine vaccination are demanded to the Ministry of Health, Labour and Welfare through local governments, and compensation is more expenses. Meanwhile, claims after the voluntary vaccination are demanded to the Pharmaceuticals and Medical Device Agency directly, and compensation is less compared with the routine vaccination.

Reducing the dose of smallpox vaccine reduces vaccine-associated morbidity without reducing vaccination success rates or immune responses.

PubMed

Couch, Robert B; Winokur, Patricia; Edwards, Kathryn M; Black, Steven; Atmar, Robert L; Stapleton, Jack T; Kissner, Jennifer M; Shinefield, Henry; Denny, Thomas N; Bybel, Michael J; Newman, Frances K; Yan, Lihan

2007-03-15

When the decision was made to prepare for a deliberate release of smallpox, the United States had approximately 15 million doses of Wyeth Dryvax vaccine, which was known to induce significant morbidity when used undiluted; Sanofi Pasteur, Inc., later identified approximately 85 million additional doses in storage. Eleven vaccine-dose groups, each with 30 vaccinia-naive subjects, were given diluted Dryvax vaccine or 1 of 2 lots of Sanofi Pasteur smallpox vaccine and were evaluated for vaccination success rates, morbidity, and immune responses. Estimated doses of 10(6.6)-10(8.2) pfu of virus/mL induced major reactions (or "takes") in 93%-100% of subjects in each dose group. No differences in vaccination take rates, lesion size, erythema, and induration or in serum neutralizing-antibody response were detected between the groups. However, systemic reactogenicity and missed activities were significantly lower for the vaccine groups given doses of 10(6.6)-10(7.2) pfu/mL than for those given doses of 10(7.6)-10(8.2) pfu/mL. These findings support the use of a higher dilution of Wyeth Dryvax vaccine and Sanofi Pasteur smallpox vaccine, given that the resulting morbidity should be significantly lower without loss of vaccine effectiveness. A plan for use of higher dilutions would create an enormous stockpile of vaccine.

Electronic patient registration and tracking at mass vaccination clinics: a clinical study.

PubMed

Billittier, Anthony J; Lupiani, Patrick; Masterson, Gary; Masterson, Tim; Zak, Christopher

2003-01-01

To protect the citizens of the United States from the use of dangerous biological agents, the Center for Disease Control and Prevention (CDC) has been actively preparing to deal with the consequences of such an attack. Their plans include the deployment of mass immunization clinics to handle postevent vaccinations. As part of the planning efforts by the Western New York Public Health Alliance, a Web-based electronic patient registration and tracking system was developed and tested at a recent trial smallpox vaccination clinic. Initial goals were to determine what the pitfalls and benefits of using such a system might be in comparison to other methods of data collection. This exercise proved that use of an electronic system capable of scanning two-dimensional bar codes was superior to both paper-based and optical character recognition (OCR) methods of data collection and management. Major improvements in speed and/or accuracy were evident in all areas of the clinic, especially in patient registration, vaccine tracking and postclinic data analysis.

Post-Marketing Surveillance of Human Rabies Diploid Cell Vaccine (Imovax) in the Vaccine Adverse Event Reporting System (VAERS) in the United States, 1990‒2015

PubMed Central

Moro, Pedro L.; Woo, Emily Jane; Paul, Wendy; Lewis, Paige; Petersen, Brett W.; Cano, Maria

2016-01-01

Background In 1980, human diploid cell vaccine (HDCV, Imovax Rabies, Sanofi Pasteur), was licensed for use in the United States. Objective To assess adverse events (AEs) after HDCV reported to the US Vaccine Adverse Event Reporting System (VAERS), a spontaneous reporting surveillance system. Methods We searched VAERS for US reports after HDCV among persons vaccinated from January 1, 1990–July 31, 2015. Medical records were requested for reports classified as serious (death, hospitalization, prolonged hospitalization, disability, life-threatening-illness), and those suggesting anaphylaxis and Guillain-Barré syndrome (GBS). Physicians reviewed available information and assigned a primary clinical category to each report using MedDRA system organ classes. Empirical Bayesian (EB) data mining was used to identify disproportional AE reporting after HDCV. Results VAERS received 1,611 reports after HDCV; 93 (5.8%) were serious. Among all reports, the three most common AEs included pyrexia (18.2%), headache (17.9%), and nausea (16.5%). Among serious reports, four deaths appeared to be unrelated to vaccination. Conclusions This 25-year review of VAERS did not identify new or unexpected AEs after HDCV. The vast majority of AEs were non-serious. Injection site reactions, hypersensitivity reactions, and non-specific constitutional symptoms were most frequently reported, similar to findings in pre-licensure studies. PMID:27410239

Post-Marketing Surveillance of Human Rabies Diploid Cell Vaccine (Imovax) in the Vaccine Adverse Event Reporting System (VAERS) in the United States, 1990‒2015.

PubMed

Moro, Pedro L; Woo, Emily Jane; Paul, Wendy; Lewis, Paige; Petersen, Brett W; Cano, Maria

2016-07-01

In 1980, human diploid cell vaccine (HDCV, Imovax Rabies, Sanofi Pasteur), was licensed for use in the United States. To assess adverse events (AEs) after HDCV reported to the US Vaccine Adverse Event Reporting System (VAERS), a spontaneous reporting surveillance system. We searched VAERS for US reports after HDCV among persons vaccinated from January 1, 1990-July 31, 2015. Medical records were requested for reports classified as serious (death, hospitalization, prolonged hospitalization, disability, life-threatening-illness), and those suggesting anaphylaxis and Guillain-Barré syndrome (GBS). Physicians reviewed available information and assigned a primary clinical category to each report using MedDRA system organ classes. Empirical Bayesian (EB) data mining was used to identify disproportional AE reporting after HDCV. VAERS received 1,611 reports after HDCV; 93 (5.8%) were serious. Among all reports, the three most common AEs included pyrexia (18.2%), headache (17.9%), and nausea (16.5%). Among serious reports, four deaths appeared to be unrelated to vaccination. This 25-year review of VAERS did not identify new or unexpected AEs after HDCV. The vast majority of AEs were non-serious. Injection site reactions, hypersensitivity reactions, and non-specific constitutional symptoms were most frequently reported, similar to findings in pre-licensure studies.

A systems approach to designing next generation vaccines: combining α-galactose modified antigens with nanoparticle platforms

NASA Astrophysics Data System (ADS)

Phanse, Yashdeep; Carrillo-Conde, Brenda R.; Ramer-Tait, Amanda E.; Broderick, Scott; Kong, Chang Sun; Rajan, Krishna; Flick, Ramon; Mandell, Robert B.; Narasimhan, Balaji; Wannemuehler, Michael J.

2014-01-01

Innovative vaccine platforms are needed to develop effective countermeasures against emerging and re-emerging diseases. These platforms should direct antigen internalization by antigen presenting cells and promote immunogenic responses. This work describes an innovative systems approach combining two novel platforms, αGalactose (αGal)-modification of antigens and amphiphilic polyanhydride nanoparticles as vaccine delivery vehicles, to rationally design vaccine formulations. Regimens comprising soluble αGal-modified antigen and nanoparticle-encapsulated unmodified antigen induced a high titer, high avidity antibody response with broader epitope recognition of antigenic peptides than other regimen. Proliferation of antigen-specific CD4+ T cells was also enhanced compared to a traditional adjuvant. Combining the technology platforms and augmenting immune response studies with peptide arrays and informatics analysis provides a new paradigm for rational, systems-based design of next generation vaccine platforms against emerging and re-emerging pathogens.

Fate of Systemically Administered Cocaine in Nonhuman Primates Treated with the dAd5GNE Anticocaine Vaccine

PubMed Central

Hicks, Martin J.; Kaminsky, Stephen M.; De, Bishnu P.; Rosenberg, Jonathan B.; Evans, Suzette M.; Foltin, Richard W.; Andrenyak, David M.; Moody, David E.; Koob, George F.; Janda, Kim D.; Ricart Arbona, Rodolfo J.; Lepherd, Michelle L.

2014-01-01

Abstract Cocaine use disorders are mediated by the cocaine blockade of the dopamine transporter in the central nervous system (CNS). On the basis of the concept that these effects could be obviated if cocaine were prevented from reaching its cognate receptors in the CNS, we have developed an anticocaine vaccine, dAd5GNE, based on a cocaine analog covalently linked to capsid proteins of an E1−E3− serotype 5 adenovirus. While the vaccine effectively blocks systemically administered cocaine from reaching the brain by mediating sequestration of the cocaine in the blood, the fact that cocaine also has significant peripheral effects raises concerns that vaccination-mediated redistribution could lead to adverse effects in the visceral organs. The distribution of systemically administered cocaine at a weight-adjusted typical human dose was evaluated along with cocaine metabolites in both dAd5GNE-vaccinated and control nonhuman primates. dAd5GNE sequestration of cocaine to the blood not only prevented cocaine access to the CNS, but also limited access of both the drug and its metabolites to other cocaine-sensitive organs. The levels of cocaine in the blood of vaccinated animals rapidly decreased, suggesting that while the antibody limits access of the drug and its active metabolites to the brain and sensitive organs of the periphery, it does not prolong drug levels in the blood compartment. Gross and histopathology of major organs found no vaccine-mediated untoward effects. These results build on our earlier measures of efficacy and demonstrate that the dAd5GNE vaccine-mediated redistribution of administered cocaine is not likely to impact the vaccine safety profile. PMID:24649839

A cell-based systems biology assessment of human blood to monitor immune responses after influenza vaccination.

PubMed

Hoek, Kristen L; Samir, Parimal; Howard, Leigh M; Niu, Xinnan; Prasad, Nripesh; Galassie, Allison; Liu, Qi; Allos, Tara M; Floyd, Kyle A; Guo, Yan; Shyr, Yu; Levy, Shawn E; Joyce, Sebastian; Edwards, Kathryn M; Link, Andrew J

2015-01-01

Systems biology is an approach to comprehensively study complex interactions within a biological system. Most published systems vaccinology studies have utilized whole blood or peripheral blood mononuclear cells (PBMC) to monitor the immune response after vaccination. Because human blood is comprised of multiple hematopoietic cell types, the potential for masking responses of under-represented cell populations is increased when analyzing whole blood or PBMC. To investigate the contribution of individual cell types to the immune response after vaccination, we established a rapid and efficient method to purify human T and B cells, natural killer (NK) cells, myeloid dendritic cells (mDC), monocytes, and neutrophils from fresh venous blood. Purified cells were fractionated and processed in a single day. RNA-Seq and quantitative shotgun proteomics were performed to determine expression profiles for each cell type prior to and after inactivated seasonal influenza vaccination. Our results show that transcriptomic and proteomic profiles generated from purified immune cells differ significantly from PBMC. Differential expression analysis for each immune cell type also shows unique transcriptomic and proteomic expression profiles as well as changing biological networks at early time points after vaccination. This cell type-specific information provides a more comprehensive approach to monitor vaccine responses.

Vaccine stockouts around the world: Are essential vaccines always available when needed?

PubMed

Lydon, Patrick; Schreiber, Benjamin; Gasca, Aurelia; Dumolard, Laure; Urfer, Daniela; Senouci, Kamel

2017-04-19

As countries rise to the challenge of implementing the priorities of this "Decade of Vaccine" and their commitments delineated in the Global Vaccine Action Plan (GVAP), many continue to face important challenges of securing a continuous supply of essential vaccine for their national immunization programme. This study provides evidence on the incidence of vaccine stockouts in countries, their root causes and their potential impact on service delivery. Vaccine stockout indicators collected from the WHO-UNICEF Joint Reporting Form (JRF) and UNICEF's Vaccine Forecasting Tool were analysed for the years covering the first half of the GVAP (2011 to 2015) and using 2010 as the baseline year. While the JRF collects annual information on national and subnational stockouts by vaccine, the UNICEF Vaccine Forecasting Tool has the advantage of requesting UNICEF procuring countries to report on the reasons underpinning any stockouts. Every year on average, one in every three WHO Member States experiences at least one stockout of at least one vaccine for at least one month. The incidence is most pronounced in Sub-Saharan Africa where 38% of countries in this area of the world report national-level stockouts. The vaccines most affected are DTP containing vaccines (often combined with HepB and Hib) and BCG. They account for respectively 43% and 31% of stockout events reported. While national level vaccine stockouts occur in countries of all income groups, middle income countries are the most affected. In 80% of cases, national level stockouts were due to reasons internal to countries. More specifically, 39% of stockouts were attributable to government funding delays, 23% were caused by delays in the procurement processes, and poor forecasting and stock management at country level accounted for an additional 18%. When a national level stockout of vaccines occurs, there is an 89% chance that a subnational stockout will occur at district level. More concerning is that if a district

Biosafety of parenteral Brucella abortus RB51 vaccine in bison calves

USGS Publications Warehouse

Roffe, T.J.; Olsen, S.C.; Gidlewski, T.; Jensen, A.E.; Palmer, M.V.; Huber, R.

1999-01-01

Vaccination is considered among the primary management tools for reducing brucellosis prevalence in Greater Yellowstone Area (GYA) ungulates. Before their use, however, vaccine safety and efficacy must be demonstrated. Twenty-seven female bison (Bison bison) calves (approx 5 months old) were vaccinated with Brucella abortus Strain RB51 (1.5 x 1010 colony forming units [CFU], subcutaneously) as part of routine management. We assessed the persistence, pathology, shedding, and transmission associated with RB51 by serial necropsy, bacteriology, histopathology, and serology of 20 of these 27 vaccinated calves, and RB51 serology of 10 nonvaccinated, commingling adult females. With the exception of 1 calf, RB51 dot-blot titers at necropsy were <1:80. Strain RB51 was cultured from lymph nodes in 4 of 4 calves at 14 weeks postvaccination (PV), 4 of 4 calves at 18 weeks PV, 1 of 4 calves at 22 weeks PV, 3 of 4 at 26 weeks PV, and 0 of 4 calves at 30 weeks PV. No gross lesions were observed. Mild histologic changes occurred only in a few draining lymph nodes early in sampling. Adverse clinical effects were not observed in vaccinates. Swabs from nasopharynx, conjunctiva, rectum, and vagina were uniformly culture negative for RB51. Strain RB51 dot-blot assays of bison cows were negative at a 1:20 dilution at 26 weeks PV. Our results suggest that RB51 persists longer in bison calves than in domestic cattle and is systemically distributed within lymphatic tissues. However, bison apparently clear the RB51 vaccine strain without shedding, transmission, or significant adverse reactions.

The Case for Adolescent HIV Vaccination in South Africa: A Cost-Effectiveness Analysis.

PubMed

Moodley, Nishila; Gray, Glenda; Bertram, Melanie

2016-01-01

Despite comprising 0.7% of the world population, South Africa is home to 18% of the global human immunodeficiency virus (HIV) prevalence. Unyielding HIV subepidemics among adolescents threaten national attempts to curtail the disease burden. Should an HIV vaccine become available, establishing its point of entry into the health system becomes a priority. This study assesses the impact of school-based HIV vaccination and explores how variations in vaccine characteristics affect cost-effectiveness. The cost per quality adjusted life year (QALY) gained associated with school-based adolescent HIV vaccination services was assessed using Markov modeling that simulated annual cycles based on national costing data. The estimation was based on a life expectancy of 70 years and employs the health care provider perspective. The simultaneous implementation of HIV vaccination services with current HIV management programs would be cost-effective, even at relatively higher vaccine cost. At base vaccine cost of US$ 12, the incremental cost effectiveness ratio (ICER) was US$ 43 per QALY gained, with improved ICER values yielded at lower vaccine costs. The ICER was sensitive to duration of vaccine mediated protection and variations in vaccine efficacy. Data from this work demonstrate that vaccines offering longer duration of protection and at lower cost would result in improved ICER values. School-based HIV vaccine services of adolescents, in addition to current HIV prevention and treatment health services delivered, would be cost-effective.

Neurologic complications of vaccinations.

PubMed

Miravalle, Augusto A; Schreiner, Teri

2014-01-01

This chapter reviews the most common neurologic disorders associated with common vaccines, evaluates the data linking the disorder with the vaccine, and discusses the potential mechanism of disease. A literature search was conducted in PubMed using a combination of the following terms: vaccines, vaccination, immunization, and neurologic complications. Data were also gathered from publications of the American Academy of Pediatrics Committee on Infectious Diseases, the World Health Organization, the US Centers for Disease Control and Prevention, and the Vaccine Adverse Event Reporting System. Neurologic complications of vaccination are rare. Many associations have been asserted without objective data to support a causal relationship. Rarely, patients with a neurologic complication will have a poor outcome. However, most patients recover fully from the neurologic complication. Vaccinations have altered the landscape of infectious disease. However, perception of risk associated with vaccinations has limited the success of disease eradication measures. Neurologic complications can be severe, and can provoke fear in potential vaccines. Evaluating whether there is causal link between neurologic disorders and vaccinations, not just temporal association, is critical to addressing public misperception of risk of vaccination. Among the vaccines available today, the cost-benefit analysis of vaccinations and complications strongly argues in favor of vaccination. © 2014 Elsevier B.V. All rights reserved.

Utilizing population variation, vaccination, and systems biology to study human immunology.

PubMed

Tsang, John S

2015-08-01

The move toward precision medicine has highlighted the importance of understanding biological variability within and across individuals in the human population. In particular, given the prevalent involvement of the immune system in diverse pathologies, an important question is how much and what information about the state of the immune system is required to enable accurate prediction of future health and response to medical interventions. Towards addressing this question, recent studies using vaccination as a model perturbation and systems-biology approaches are beginning to provide a glimpse of how natural population variation together with multiplexed, high-throughput measurement and computational analysis can be used to uncover predictors of immune response quality in humans. Here I discuss recent developments in this emerging field, with emphasis on baseline correlates of vaccination responses, sources of immune-state variability, as well as relevant features of study design, data generation, and computational analysis. Copyright © 2015 The Author. Published by Elsevier Ltd.. All rights reserved.

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

PubMed

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

2015-07-09

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

Systemic immune response and virus persistence after foot-and-mouth disease virus infection of naïve cattle and cattle vaccinated with a homologous adenovirus-vectored vaccine

USDA-ARS?s Scientific Manuscript database

In order to investigate host factors associated with the establishment of persistent foot-and-mouth disease virus (FMDV) infection, the systemic immune response to vaccination and challenge was studied in 47 Holstein steers. Eighteen steers which had received one dose of recombinant FMDV A vaccine t...

Flying vaccinator; a transgenic mosquito delivers a Leishmania vaccine via blood feeding.

PubMed

Yamamoto, D S; Nagumo, H; Yoshida, S

2010-06-01

'Flying vaccinator' is the concept of using genetically engineered hematophagous insects to deliver vaccines. Here we show the generation of a transgenic anopheline mosquito that expresses the Leishmania vaccine candidate, SP15, fused to monomeric red fluorescent protein (mDsRed) in its salivary glands. Importantly, mice bitten repeatedly by the transgenic mosquitoes raised anti-SP15 antibodies, indicating delivery of SP15 via blood feeding with its immunogenicity intact. Thus, this technology makes possible the generation of transgenic mosquitoes that match the original concept of a 'flying vaccinator'. However, medical safety issues and concerns about informed consent mitigate the use of the 'flying vaccinator' as a method to deliver vaccines. We propose that this expression system could be applied to elucidate saliva-malaria sporozoite interactions.

System factors to explain H1N1 state vaccination rates for adults in US emergency response to pandemic.

PubMed

Davila-Payan, Carlo; Swann, Julie; Wortley, Pascale M

2014-05-23

During the 2009-2010 H1N1 pandemic, vaccine in short supply was allocated to states pro rata by population, yet the vaccination rates of adults differed by state. States also differed in their campaign processes and decisions. Analyzing the campaign provides an opportunity to identify specific approaches that may result in higher vaccine uptake in a future event of this nature. To determine supply chain and system factors associated with higher state H1N1 vaccination coverage for adults in a system where vaccine was in short supply. Regression analysis of factors predicting state-specific H1N1 vaccination coverage in adults. Independent variables included state campaign information, demographics, preventive or health-seeking behavior, preparedness funding, providers, state characteristics, and H1N1-specific state data. The best model explained the variation in state-specific adult vaccination coverage with an adjusted R-squared of 0.76. We found that higher H1N1 coverage of adults is associated with program aspects including shorter lead-times (i.e., the number of days between when doses were allocated to a state and were shipped, including the time for states to order the doses) and less vaccine directed to specialist locations. Higher vaccination coverage is also positively associated with the maximum number of ship-to locations, past seasonal influenza vaccination coverage, the percentage of women with a Pap smear, the percentage of the population that is Hispanic, and negatively associated with a long duration of the epidemic peak. Long lead-times may be a function of system structure or of efficiency and may suggest monitoring or redesign of distribution processes. Sending vaccine to sites with broad access could be useful when covering a general population. Existing infrastructure may be reflected in the maximum number of ship-to locations, so strengthening routine influenza vaccination programs may help during emergency vaccinations also. Future research

Factors affecting vaccine handling and storage practices among immunization service providers in Ibadan, Oyo State, Nigeria.

PubMed

Dairo, David M; Osizimete, Oyarebu E

2016-06-01

Improper handling has been identified as one of the major reasons for the decline in vaccine potency at the time of administration. Loss of potency becomes evident when immunised individuals contract the diseases the vaccines were meant to prevent. Assessing the factors associated with vaccine handling and storage practices. This was a cross-sectional study. Three-stage sampling was used to recruit 380 vaccine handlers from 273 health facilities from 11 Local Government areas in Ibadan. Data was analysed using SPSS version 16. Seventy-three percent were aware of vaccine handling and storage guidelines with 68.4% having ever read such guidelines. Only 15.3% read a guideline less than 1 month prior to the study. About 65.0% had received training on vaccine management. Incorrect handling practices reported included storing injections with vaccines (13.7%) and maintaining vaccine temperature using ice blocks (7.6%). About 43.0% had good knowledge of vaccine management, while 66.1% had good vaccine management practices. Respondents who had good knowledge of vaccine handling and storage [OR=10.0, 95%CI (5.28 - 18.94), p < 0.001] and had received formal training on vaccine management [OR=5.3, 95%CI (2.50 - 11.14), p< 0.001] were more likely to have good vaccine handling and storage practices. Regular training is recommended to enhance vaccine handling and storage practices.

Post-licensure safety surveillance of zoster vaccine live (Zostavax®) in the United States, Vaccine Adverse Event Reporting System (VAERS), 2006-2015.

PubMed

Miller, Elaine R; Lewis, Paige; Shimabukuro, Tom T; Su, John; Moro, Pedro; Woo, Emily Jane; Jankosky, Christopher; Cano, Maria

2018-03-26

Herpes zoster (HZ), or shingles, is caused by reactivation of varicella-zoster virus in latently infected individuals. Live-attenuated HZ vaccine (zoster vaccine live, ZVL) is approved in the United States for persons aged ≥50 years and recommended by the CDC for persons ≥60 years. We analyzed U.S. reports of adverse events (AEs) following ZVL submitted to the Vaccine Adverse Event Reporting System (VAERS), a spontaneous reporting system to monitor vaccine safety, for persons vaccinated May 1, 2006, through January 31, 2015. We conducted descriptive analysis, clinical reviews of reports with selected pre-specified conditions, and empirical Bayesian data mining. VAERS received 23,092 reports following ZVL, of which 22,120 (96%) were classified as non-serious. Of reports where age was documented (n = 18,817), 83% were in persons aged ≥60 years. Reporting rates of AEs were 106 and 4.4 per 100,000 ZVL doses distributed for all reports and serious reports, respectively. When ZVL was administered alone among persons aged ≥50 years, injection site erythema (27%), HZ (17%), injection site swelling (17%), and rash (14%) were the most commonly reported symptoms among non-serious reports; HZ (29%), pain (18%), and rash (16%) were the most commonly reported symptoms among serious reports. Six reports included laboratory evidence of vaccine-strain varicella-zoster virus (Oka/Merck strain) infection; AEs included HZ, HZ- or varicella-like illness, and local reaction with vesicles. In our review of reports of death with sufficient information to determine cause (n = 46, median age 75 years), the most common causes were heart disease (n = 28), sepsis (n = 4), and stroke (n = 3). Empirical Bayesian data mining did not detect new or unexpected safety signals. Findings from our safety review of ZVL are consistent with those from pre-licensure clinical trials and other post-licensure assessments. Transient injection-site reactions, HZ, and rashes were most frequently

Strengthening capacity for AIDS vaccine research: analysis of the Pfizer Global Health Fellows Program and the International AIDS Vaccine Initiative

PubMed Central

2013-01-01

Background Industry partnerships can help leverage resources to advance HIV/AIDS vaccine research, service delivery, and policy advocacy goals. This often involves capacity building for international and local non-governmental organizations (NGOs). International volunteering is increasingly being used as a capacity building strategy, yet little is known about how corporate volunteers help to improve performance of NGOs in the fight against HIV/AIDS. Methods This case study helps to extend our understanding by analyzing how the Pfizer Global Health Fellows (GHF) program helped develop capacity of the International AIDS Vaccine Initiative (IAVI), looking specifically at Fellowship activities in South Africa, Kenya, and Uganda. From 2005–2009, 8 Pfizer GHF worked with IAVI and local research centers to strengthen capacity to conduct and monitor vaccine trials to meet international standards and expand trial activities. Data collection for the case study included review of Fellow job descriptions, online journals, evaluation reports, and interviews with Fellows and IAVI staff. Qualitative methods were used to analyze factors which influenced the process and outcomes of capacity strengthening. Results Fellows filled critical short-term expert staffing needs at IAVI as well as providing technical assistance and staff development activities. Capacity building included assistance in establishing operating procedures for the start-up period of research centers; training staff in Good Clinical Practice (GCP); developing monitoring capacity (staff and systems) to assure that centers are audit-ready at all times; and strategic planning for data management systems. Factors key to the success of volunteering partnerships included similarities in mission between the corporate and NGO partners, expertise and experience of Fellows, and attitudes of partner organization staff. Conclusion By developing standard operating procedures, ensuring that monitoring and regulatory

Strengthening capacity for AIDS vaccine research: analysis of the Pfizer Global Health Fellows program and the International AIDS Vaccine Initiative.

PubMed

Vian, Taryn; Koseki, Sayaka; Feeley, Frank G; Beard, Jennifer

2013-10-02

Industry partnerships can help leverage resources to advance HIV/AIDS vaccine research, service delivery, and policy advocacy goals. This often involves capacity building for international and local non-governmental organizations (NGOs). International volunteering is increasingly being used as a capacity building strategy, yet little is known about how corporate volunteers help to improve performance of NGOs in the fight against HIV/AIDS. This case study helps to extend our understanding by analyzing how the Pfizer Global Health Fellows (GHF) program helped develop capacity of the International AIDS Vaccine Initiative (IAVI), looking specifically at Fellowship activities in South Africa, Kenya, and Uganda. From 2005-2009, 8 Pfizer GHF worked with IAVI and local research centers to strengthen capacity to conduct and monitor vaccine trials to meet international standards and expand trial activities. Data collection for the case study included review of Fellow job descriptions, online journals, evaluation reports, and interviews with Fellows and IAVI staff. Qualitative methods were used to analyze factors which influenced the process and outcomes of capacity strengthening. Fellows filled critical short-term expert staffing needs at IAVI as well as providing technical assistance and staff development activities. Capacity building included assistance in establishing operating procedures for the start-up period of research centers; training staff in Good Clinical Practice (GCP); developing monitoring capacity (staff and systems) to assure that centers are audit-ready at all times; and strategic planning for data management systems. Factors key to the success of volunteering partnerships included similarities in mission between the corporate and NGO partners, expertise and experience of Fellows, and attitudes of partner organization staff. By developing standard operating procedures, ensuring that monitoring and regulatory compliance systems were in place, training

Quantifying the Value of Perfect Information in Emergency Vaccination Campaigns.

PubMed

Bradbury, Naomi V; Probert, William J M; Shea, Katriona; Runge, Michael C; Fonnesbeck, Christopher J; Keeling, Matt J; Ferrari, Matthew J; Tildesley, Michael J

2017-02-01

Foot-and-mouth disease outbreaks in non-endemic countries can lead to large economic costs and livestock losses but the use of vaccination has been contentious, partly due to uncertainty about emergency FMD vaccination. Value of information methods can be applied to disease outbreak problems such as FMD in order to investigate the performance improvement from resolving uncertainties. Here we calculate the expected value of resolving uncertainty about vaccine efficacy, time delay to immunity after vaccination and daily vaccination capacity for a hypothetical FMD outbreak in the UK. If it were possible to resolve all uncertainty prior to the introduction of control, we could expect savings of £55 million in outbreak cost, 221,900 livestock culled and 4.3 days of outbreak duration. All vaccination strategies were found to be preferable to a culling only strategy. However, the optimal vaccination radius was found to be highly dependent upon vaccination capacity for all management objectives. We calculate that by resolving the uncertainty surrounding vaccination capacity we would expect to return over 85% of the above savings, regardless of management objective. It may be possible to resolve uncertainty about daily vaccination capacity before an outbreak, and this would enable decision makers to select the optimal control action via careful contingency planning.

Quantifying the Value of Perfect Information in Emergency Vaccination Campaigns

PubMed Central

Probert, William J. M.; Shea, Katriona; Fonnesbeck, Christopher J.; Ferrari, Matthew J.; Tildesley, Michael J.

2017-01-01

Foot-and-mouth disease outbreaks in non-endemic countries can lead to large economic costs and livestock losses but the use of vaccination has been contentious, partly due to uncertainty about emergency FMD vaccination. Value of information methods can be applied to disease outbreak problems such as FMD in order to investigate the performance improvement from resolving uncertainties. Here we calculate the expected value of resolving uncertainty about vaccine efficacy, time delay to immunity after vaccination and daily vaccination capacity for a hypothetical FMD outbreak in the UK. If it were possible to resolve all uncertainty prior to the introduction of control, we could expect savings of £55 million in outbreak cost, 221,900 livestock culled and 4.3 days of outbreak duration. All vaccination strategies were found to be preferable to a culling only strategy. However, the optimal vaccination radius was found to be highly dependent upon vaccination capacity for all management objectives. We calculate that by resolving the uncertainty surrounding vaccination capacity we would expect to return over 85% of the above savings, regardless of management objective. It may be possible to resolve uncertainty about daily vaccination capacity before an outbreak, and this would enable decision makers to select the optimal control action via careful contingency planning. PMID:28207777

Economics of animal vaccination.

PubMed

McLeod, A; Rushton, J

2007-08-01

This paper describes the steps that might be used in assessing the economic justification for using vaccination to control animal disease, and the way that vaccination is financed and administered. It describes decisions that have been taken with respect to preserving international trade, and issues related to protection of livelihoods. Regardless of the motivation for vaccination, its costs can usually be shared between the public and private sectors. Cost-effective vaccination requires methods of delivery to be adapted to livestock production systems. The paper concludes by suggesting questions around the use of vaccination that would merit further economic analysis.

Cost analysis of an integrated vaccine-preventable disease surveillance system in Costa Rica✩

PubMed Central

Toscano, C.M.; Vijayaraghavan, M.; Salazar-Bolaños, H.M.; Bolaños-Acuña, H.M.; Ruiz-González, A.I.; Barrantes-Solis, T.; Fernández-Vargas, I.; Panero, M.S.; de Oliveira, L.H.; Hyde, T.B.

2015-01-01

Introduction Following World Health Organization recommendations set forth in the Global Framework for Immunization Monitoring and Surveillance, Costa Rica in 2009 became the first country to implement integrated vaccine-preventable disease (iVPD) surveillance, with support from the U.S. Centers for Disease Control and Prevention (CDC) and the Pan American Health Organization (PAHO). As surveillance for diseases prevented by new vaccines is integrated into existing surveillance systems, these systems could cost more than routine surveillance for VPDs targeted by the Expanded Program on Immunization. Objectives We estimate the costs associated with establishing and subsequently operating the iVPD surveillance system at a pilot site in Costa Rica. Methods We retrospectively collected data on costs incurred by the institutions supporting iVPD surveillance during the preparatory (January 2007 through August 2009) and implementation (September 2009 through August 2010) phases of the iVPD surveillance project in Costa Rica. These data were used to estimate costs for personnel, meetings, infrastructure, office equipment and supplies, transportation, and laboratory facilities. Costs incurred by each of the collaborating institutions were also estimated. Results During the preparatory phase, the estimated total cost was 128,000 U.S. dollars (US$), including 64% for personnel costs. The preparatory phase was supported by CDC and PAHO. The estimated cost for 1 year of implementation was US$ 420,000, including 58% for personnel costs, 28% for laboratory costs, and 14% for meeting, infrastructure, office, and transportation costs combined. The national reference laboratory and the PAHO Costa Rica office incurred 64% of total costs, and other local institutions supporting iVPD surveillance incurred the remaining 36%. Conclusions Countries planning to implement iVPD surveillance will require adequate investments in human resources, laboratories, data management, reporting, and

Cost analysis of an integrated vaccine-preventable disease surveillance system in Costa Rica.

PubMed

Toscano, C M; Vijayaraghavan, M; Salazar-Bolaños, H M; Bolaños-Acuña, H M; Ruiz-González, A I; Barrantes-Solis, T; Fernández-Vargas, I; Panero, M S; de Oliveira, L H; Hyde, T B

2013-07-02

Following World Health Organization recommendations set forth in the Global Framework for Immunization Monitoring and Surveillance, Costa Rica in 2009 became the first country to implement integrated vaccine-preventable disease (iVPD) surveillance, with support from the U.S. Centers for Disease Control and Prevention (CDC) and the Pan American Health Organization (PAHO). As surveillance for diseases prevented by new vaccines is integrated into existing surveillance systems, these systems could cost more than routine surveillance for VPDs targeted by the Expanded Program on Immunization. We estimate the costs associated with establishing and subsequently operating the iVPD surveillance system at a pilot site in Costa Rica. We retrospectively collected data on costs incurred by the institutions supporting iVPD surveillance during the preparatory (January 2007 through August 2009) and implementation (September 2009 through August 2010) phases of the iVPD surveillance project in Costa Rica. These data were used to estimate costs for personnel, meetings, infrastructure, office equipment and supplies, transportation, and laboratory facilities. Costs incurred by each of the collaborating institutions were also estimated. During the preparatory phase, the estimated total cost was 128,000 U.S. dollars (US$), including 64% for personnel costs. The preparatory phase was supported by CDC and PAHO. The estimated cost for 1 year of implementation was US$ 420,000, including 58% for personnel costs, 28% for laboratory costs, and 14% for meeting, infrastructure, office, and transportation costs combined. The national reference laboratory and the PAHO Costa Rica office incurred 64% of total costs, and other local institutions supporting iVPD surveillance incurred the remaining 36%. Countries planning to implement iVPD surveillance will require adequate investments in human resources, laboratories, data management, reporting, and investigation. Our findings will be valuable for

Removal of gelatin from live vaccines and DTaP-an ultimate solution for vaccine-related gelatin allergy.

PubMed

Kuno-Sakai, Harumi; Kimura, Mikio

2003-12-01

From the early 1990s infants started to receive acellular pertussis vaccine combined with diphtheria and tetanus toxoids (DTaP) before live vaccines such as measles, rubella, and mumps vaccines, which contained gelatin as a stabilizer. Then, an increasing number of cases of anaphylactic/allergic reactions to those live vaccines were reported. Almost all these cases had a previous history of receiving three or four doses of DTaP containing gelatin.Anaphylactic/allergic reactions to live measles vaccine were analyzed using information obtained from the Reporting System, a retrospective study, as well as from the Monitoring System, a prospective study. Dramatic decreases in anaphylactic/allergic reactions to live measles vaccines were observed immediately after each manufacturer marketed gelatin-free or gelatin (hypo-allergic)-containing live measles vaccine, and since the end of 1998 reports on anaphylactic/allergic reactions to live measles vaccine have almost ceased.

International Consensus (ICON): allergic reactions to vaccines.

PubMed

Dreskin, Stephen C; Halsey, Neal A; Kelso, John M; Wood, Robert A; Hummell, Donna S; Edwards, Kathryn M; Caubet, Jean-Christoph; Engler, Renata J M; Gold, Michael S; Ponvert, Claude; Demoly, Pascal; Sanchez-Borges, Mario; Muraro, Antonella; Li, James T; Rottem, Menachem; Rosenwasser, Lanny J

2016-01-01

Routine immunization, one of the most effective public health interventions, has effectively reduced death and morbidity due to a variety of infectious diseases. However, allergic reactions to vaccines occur very rarely and can be life threatening. Given the large numbers of vaccines administered worldwide, there is a need for an international consensus regarding the evaluation and management of allergic reactions to vaccines. Following a review of the literature, and with the active participation of representatives from the World Allergy Organization (WAO), the European Academy of Allergy and Clinical Immunology (EAACI), the American Academy of Allergy, Asthma, and Immunology (AAAAI), and the American College of Allergy, Asthma, and Immunology (ACAAI), the final committee was formed with the purpose of having members who represented a wide-range of countries, had previously worked on vaccine safety, and included both allergist/immunologists as well as vaccinologists. Consensus was reached on a variety of topics, including: definition of immediate allergic reactions, including anaphylaxis, approaches to distinguish association from causality, approaches to patients with a history of an allergic reaction to a previous vaccine, and approaches to patients with a history of an allergic reaction to components of vaccines. This document provides comprehensive and internationally accepted guidelines and access to on-line documents to help practitioners around the world identify allergic reactions following immunization. It also provides a framework for the evaluation and further management of patients who present either following an allergic reaction to a vaccine or with a history of allergy to a component of vaccines.

Pathogen-mimicking vaccine delivery system designed with a bioactive polymer (inulin acetate) for robust humoral and cellular immune responses.

PubMed

Kumar, Sunny; Kesharwani, Siddharth S; Kuppast, Bhimanna; Bakkari, Mohammed Ali; Tummala, Hemachand

2017-09-10

New and improved vaccines are needed against challenging diseases such as malaria, tuberculosis, Ebola, influenza, AIDS, and cancer. The majority of existing vaccine adjuvants lack the ability to significantly stimulate the cellular immune response, which is required to prevent the aforementioned diseases. This study designed a novel particulate based pathogen-mimicking vaccine delivery system (PMVDS) to target antigen-presenting-cells (APCs) such as dendritic cells. The uniqueness of PMVDS is that the polymer used to prepare the delivery system, Inulin Acetate (InAc), activates the innate immune system. InAc was synthesized from the plant polysaccharide, inulin. PMVDS provided improved and persistent antigen delivery to APCs as an efficient vaccine delivery system, and simultaneously, activated Toll-Like Receptor-4 (TLR-4) on APCs to release chemokine's/cytokines as an immune-adjuvant. Through this dual mechanism, PMVDS robustly stimulated both the humoral (>32 times of IgG1 levels vs alum) and the cell-mediated immune responses against the encapsulated antigen (ovalbumin) in mice. More importantly, PMVDS stimulated both cytotoxic T cells and natural killer cells of cell-mediated immunity to provide tumor (B16-ova-Melanoma) protection in around 40% of vaccinated mice and significantly delayed tumor progression in rest of the mice. PMVDS is a unique bio-active vaccine delivery technology with broader applications for vaccines against cancer and several intracellular pathogens, where both humoral and cellular immune responses are desired. Copyright © 2017 Elsevier B.V. All rights reserved.

Global Foot-and-Mouth Disease Research Update and Gap Analysis: 3 - Vaccines.

PubMed

Robinson, L; Knight-Jones, T J D; Charleston, B; Rodriguez, L L; Gay, C G; Sumption, K J; Vosloo, W

2016-06-01

This study assessed research knowledge gaps in the field of FMDV (foot-and-mouth disease virus) vaccines. The study took the form of a literature review (2011-15) combined with research updates collected in 2014 from 33 institutes from across the world. Findings were used to identify priority areas for future FMD vaccine research. Vaccines play a vital role in FMD control, used both to limit the spread of the virus during epidemics in FMD-free countries and as the mainstay of disease management in endemic regions, particularly where sanitary controls are difficult to apply. Improvements in the performance or cost-effectiveness of FMD vaccines will allow more widespread and efficient disease control. FMD vaccines have changed little in recent decades, typically produced by inactivation of whole virus, the quantity and stability of the intact viral capsids in the final preparation being key for immunogenicity. However, these are exciting times and several promising novel FMD vaccine candidates have recently been developed. This includes the first FMD vaccine licensed for manufacture and use in the USA; this adenovirus-vectored FMD vaccine causes in vivo expression of viral capsids in vaccinated animals. Another promising vaccine candidate comprises stabilized empty FMDV capsids produced in vitro in a baculovirus expression system. Recombinant technologies are also being developed to improve otherwise conventionally produced inactivated vaccines, for example, by creating a chimeric vaccine virus to increase capsid stability and by inserting sequences into the vaccine virus for desired antigen expression. Other important areas of ongoing research include enhanced adjuvants, vaccine quality control procedures and predicting vaccine protection from immune correlates, thus reducing dependency on animal challenge studies. Globally, the degree of independent vaccine evaluation is highly variable, and this is essential for vaccine quality. Previously neglected, the

Anthrax vaccination strategies

PubMed Central

Cybulski, Robert J.; Sanz, Patrick; O'Brien, Alison D.

2009-01-01

The biological attack conducted through the U.S. postal system in 2001 broadened the threat posed by anthrax from one pertinent mainly to soldiers on the battlefield to one understood to exist throughout our society. The expansion of the threatened population placed greater emphasis on the reexamination of how we vaccinate against Bacillus anthracis. The currently-licensed Anthrax Vaccine, Adsorbed (AVA) and Anthrax Vaccine, Precipitated (AVP) are capable of generating a protective immune response but are hampered by shortcomings that make their widespread use undesirable or infeasible. Efforts to gain U.S. Food and Drug Administration (FDA) approval for licensure of a second generation recombinant protective antigen (rPA)-based anthrax vaccine are ongoing. However, this vaccine's reliance on the generation of a humoral immune response against a single virulence factor has led a number of scientists to conclude that the vaccine is likely not the final solution to optimal anthrax vaccine design. Other vaccine approaches, which seek a more comprehensive immune response targeted at multiple components of the B. anthracis organism, are under active investigation. This review seeks to summarize work that has been done to build on the current PA-based vaccine methodology and to evaluate the search for future anthrax prophylaxis strategies. PMID:19729034

Vaccination coverage and susceptibility against vaccine-preventable diseases of healthcare students in Athens, Greece.

PubMed

Karageorgou, Katerina; Katerelos, Panos; Efstathiou, Andreas; Theodoridou, Maria; Maltezou, Helena C

2014-09-03

Vaccination of healthcare students is important to protect them from acquiring and transmitting vaccine-preventable diseases (VPDs) to high-risk patients and other healthcare workers (HCWs). The aim of the current study was to estimate the vaccination coverage, the susceptibility against VPDs, the knowledge and attitudes toward vaccinations of healthcare students studying at the Athens Technological Educational Institute. The study was conducted during the academic year 2012-2013 using a standardized questionnaire. The mean knowledge score (correct answers) of healthcare students about the vaccines that are recommended by the Greek Ministry of Health for HCWs was 41%. Completed vaccination rates range from 19.6% for varicella to 80.2% for tetanus-diphtheria. A history of measles, mumps, rubella, varicella, hepatitis A, hepatitis B, or pertussis was reported by 8.2%, 4%, 5.4%, 70.4%, 1.5%, 0%, and 3% of students, respectively. Susceptibility rates were 20.5% against measles, 26.4% against mumps, 13.9% against rubella, 15.7% against varicella, 47.8% against hepatitis A, 17.3% against hepatitis B, and 19.8% against tetanus-diphtheria. Mandatory vaccination of HCWs was supported by 145 (96.7%) students. There are significant immunity gaps against all VPDs among healthcare students in Athens. A system to easily identify non-immune students should be established in association with efficient reminder systems. Education of healthcare students about VPDs and vaccines will improve their attitudes toward vaccinations and their vaccination coverage. Mandatory vaccinations should be considered for HCWs in order to promote safety within healthcare facilities. Copyright © 2014 Elsevier Ltd. All rights reserved.

Reasons for non-vaccination against HPV and future vaccination intentions among 19-26 year-old women.

PubMed

Zimet, Gregory D; Weiss, Thomas W; Rosenthal, Susan L; Good, Margaret B; Vichnin, Michelle D

2010-09-01

Despite CDC recommendations regarding universal catch-up vaccination against human papillomavirus (HPV), only about ten percent of young adult women in the United States have been vaccinated. The purpose of this study was to better understand reasons for non-vaccination among insured 19-26 year-old women and to evaluate future vaccination intentions. We used an administrative claims database from a large US managed care plan to identify women aged 19-26 for receipt of a mailed survey. From a sample of 1,375 women with no evidence of HPV vaccination from June 1, 2006 through April 30, 2007, 222 completed surveys were received, of which 185 were eligible for this analysis. The main outcome measures were unvaccinated women's attitudes and vaccine awareness, likelihood of future action regarding the vaccine, and reasons for inaction. Among the 185 non-vaccinees, 25.4% were married, 83.2% were white, and 89.2% had a college or higher level education. The vaccine was described as very important by 32.4% of subjects, and 30.1% had discussed the vaccine with a doctor and received a doctor's recommendation. Half or fewer of respondents were "very" or "extremely" likely to discuss the vaccine with their doctor (50.0%), do additional research on the vaccine (42.6%), ask a doctor to get the vaccine (37.5%), or make an appointment to get the vaccine (27.8%), while 48.0% were "somewhat", "very", or "extremely" likely to do nothing to get the vaccine. Among the latter, reasons for taking no action included being married or in a monogamous relationship (54.9%), belief that the vaccine is too new (35.4%), not having enough information about the vaccine (31.7%), concerns about side effects (24.4%), and uncertainty about insurance coverage (24.4%). Educational interventions may be needed to enhance HPV vaccination rates among 19-26 year-old women, particularly regarding information about vaccine safety, vaccine efficacy, insurance coverage, and the value of vaccination to women in

Reasons for non-vaccination against HPV and future vaccination intentions among 19-26 year-old women

PubMed Central

2010-01-01

Background Despite CDC recommendations regarding universal catch-up vaccination against human papillomavirus (HPV), only about ten percent of young adult women in the United States have been vaccinated. The purpose of this study was to better understand reasons for non-vaccination among insured 19-26 year-old women and to evaluate future vaccination intentions. Methods We used an administrative claims database from a large US managed care plan to identify women aged 19-26 for receipt of a mailed survey. From a sample of 1,375 women with no evidence of HPV vaccination from June 1, 2006 through April 30, 2007, 222 completed surveys were received, of which 185 were eligible for this analysis. The main outcome measures were unvaccinated women's attitudes and vaccine awareness, likelihood of future action regarding the vaccine, and reasons for inaction. Results Among the 185 non-vaccinees, 25.4% were married, 83.2% were white, and 89.2% had a college or higher level education. The vaccine was described as very important by 32.4% of subjects, and 30.1% had discussed the vaccine with a doctor and received a doctor's recommendation. Half or fewer of respondents were "very" or "extremely" likely to discuss the vaccine with their doctor (50.0%), do additional research on the vaccine (42.6%), ask a doctor to get the vaccine (37.5%), or make an appointment to get the vaccine (27.8%), while 48.0% were "somewhat", "very", or "extremely" likely to do nothing to get the vaccine. Among the latter, reasons for taking no action included being married or in a monogamous relationship (54.9%), belief that the vaccine is too new (35.4%), not having enough information about the vaccine (31.7%), concerns about side effects (24.4%), and uncertainty about insurance coverage (24.4%). Conclusions Educational interventions may be needed to enhance HPV vaccination rates among 19-26 year-old women, particularly regarding information about vaccine safety, vaccine efficacy, insurance coverage, and

Herpes zoster vaccine effectiveness and manifestations of herpes zoster and associated pain by vaccination status.

PubMed

Marin, Mona; Yawn, Barbara P; Hales, Craig M; Wollan, Peter C; Bialek, Stephanie R; Zhang, John; Kurland, Marge J; Harpaz, Rafael

2015-01-01

Options for managing herpes zoster (HZ)-related pain and complications have limited effectiveness, making HZ prevention through vaccination an important strategy. Limited data are available on HZ vaccine effectiveness against confirmed HZ and manifestations of HZ among vaccinated persons. We conducted a matched case-control study to assess HZ vaccine effectiveness for prevention of HZ and other HZ-related outcomes and a cohort study of persons with HZ to compare HZ-related outcomes by vaccination status. Cases were identified through active surveillance among persons age ≥ 60 years with HZ onset and health-care encounters during 2010-2011 in Southeastern Minnesota. Controls were age- and sex-matched to cases. Data were collected by medical record review and from participants via interviews and daily pain diaries. 266 HZ case-patients and 362 matched controls were enrolled in the vaccine effectiveness studies and 303 case-patients in the cohort study of HZ characteristics by vaccination status. Vaccination was associated with 54% (95% CI:32%-69%) reduction in HZ incidence, 58% (95% CI:31%-75%) reduction in HZ prodromal symptoms, and 70% (95% CI:33%-87%) reduction in medically-attended prodrome. HZ vaccine was statistically significant effective at preventing postherpetic neuralgia (PHN) measured at 30 d after rash onset, 61% (95% CI: 22%-80%). Among persons who developed HZ, no differences were found by vaccination status in severity or duration of HZ pain after rash onset. In this population-based study, HZ vaccination was associated with >50% reduction in HZ, HZ prodrome, and medically-attended prodrome.

Herpes zoster vaccine effectiveness and manifestations of herpes zoster and associated pain by vaccination status

PubMed Central

Marin, Mona; Yawn, Barbara P; Hales, Craig M; Wollan, Peter C; Bialek, Stephanie R; Zhang, John; Kurland, Marge J; Harpaz, Rafael

2015-01-01

Options for managing herpes zoster (HZ)-related pain and complications have limited effectiveness, making HZ prevention through vaccination an important strategy. Limited data are available on HZ vaccine effectiveness against confirmed HZ and manifestations of HZ among vaccinated persons. We conducted a matched case-control study to assess HZ vaccine effectiveness for prevention of HZ and other HZ-related outcomes and a cohort study of persons with HZ to compare HZ-related outcomes by vaccination status. Cases were identified through active surveillance among persons age ≥60 years with HZ onset and health-care encounters during 2010-2011 in Southeastern Minnesota. Controls were age- and sex-matched to cases. Data were collected by medical record review and from participants via interviews and daily pain diaries. 266 HZ case-patients and 362 matched controls were enrolled in the vaccine effectiveness studies and 303 case-patients in the cohort study of HZ characteristics by vaccination status. Vaccination was associated with 54% (95% CI:32%-69%) reduction in HZ incidence, 58% (95% CI:31%-75%) reduction in HZ prodromal symptoms, and 70% (95% CI:33%-87%) reduction in medically-attended prodrome. HZ vaccine was statistically significant effective at preventing postherpetic neuralgia (PHN) measured at 30 d after rash onset, 61% (95% CI: 22%-80%). Among persons who developed HZ, no differences were found by vaccination status in severity or duration of HZ pain after rash onset. In this population-based study, HZ vaccination was associated with >50% reduction in HZ, HZ prodrome, and medically-attended prodrome. PMID:25806911

Evaluating the promise of recombinant transmissible vaccines

PubMed Central

Basinski, Andrew J.; Varrelman, Tanner J.; Smithson, Mark W.; May, Ryan H.; Remien, Christopher H.; Nuismer, Scott L.

2018-01-01

Transmissible vaccines have the potential to revolutionize infectious disease control by reducing the vaccination effort required to protect a population against a disease. Recent efforts to develop transmissible vaccines focus on recombinant transmissible vaccine designs (RTVs) because they pose reduced risk if intra-host evolution causes the vaccine to revert to its vector form. However, the shared antigenicity of the vaccine and vector may confer vaccine-immunity to hosts infected with the vector, thwarting the ability of the vaccine to spread through the population. We build a mathematical model to test whether a RTV can facilitate disease management in instances where reversion is likely to introduce the vector into the population or when the vector organism is already established in the host population, and the vector and vaccine share perfect cross-immunity. Our results show that a RTV can autonomously eradicate a pathogen, or protect a population from pathogen invasion, when cross-immunity between vaccine and vector is absent. If cross-immunity between vaccine and vector exists, however, our results show that a RTV can substantially reduce the vaccination effort necessary to control or eradicate a pathogen only when continuously augmented with direct manual vaccination. These results demonstrate that estimating the extent of cross-immunity between vector and vaccine is a critical step in RTV design, and that herpesvirus vectors showing facile reinfection and weak cross-immunity are promising. PMID:29279283

Fish Vaccines: Current State and Future Trends

USDA-ARS?s Scientific Manuscript database

A vaccine is a preventive tool used in a health management strategy for the control of infectious diseases. For more than 100 years, vaccines have proved to be effective for preventing infectious disease outbreaks in humans, poultry and other food animals. In aquaculture, the development and use of...

Managing controversy through consultation: a qualitative study of communication and trust around MMR vaccination decisions

PubMed Central

McMurray, Robert; Cheater, Francine M; Weighall, Anna; Nelson, Carolyn; Schweiger, Martin; Mukherjee, Suzanne

2004-01-01

Background: Controversy over the measles, mumps, and rubella (MMR) vaccine has reduced uptake, raising concerns of a future disease epidemic. Aims: To explore parents' accounts of decision making relating to the MMR vaccine controversy, identifying uptake determinants and education needs. Design of study: Qualitative interviews analysed using the ‘framework’ approach. Setting: Five general practices in the Leeds area, 2002–2003. Method: Sixty-nine interviews conducted with parents of children aged between 4 and 5 years, and 12 interviews with primary care practitioners, managers and immunisation coordinators serving participating sites. Participants were interviewed one-to-one in a place of their choice. Results: The vaccination decision is primarily a function of parental assessments of the relative acceptability and likelihood of possible outcomes. For most parents the evidence of science and medicine plays little role in the decision. Although local general practitioners and health visitors are trusted information sources, the influence of primary care providers on the vaccination decision is limited by concerns over consultation legitimacy, discussion opportunity, and perceptions of financial and political partiality. Parents and practitioners identify a need for new approaches to support decisions and learning when faced with this and similar healthcare controversies. These include new collaborative approaches to information exchange designed to transform rather than supplant existing parent knowledge as part of an ongoing learning process. Conclusion: The study identified new ways in which parents and practitioners need to be supported in order to increase understanding of medical science and secure more informed decisions in the face of health controversy. PMID:15239914

Vaccines against Ebola virus.

PubMed

Venkatraman, Navin; Silman, Daniel; Folegatti, Pedro M; Hill, Adrian V S

2017-08-02

We have just witnessed the largest and most devastating outbreak of Ebola virus disease, which highlighted the urgent need for development of an efficacious vaccine that could be used to curtail future outbreaks. Prior to 2014, there had been limited impetus worldwide to develop a vaccine since the virus was first discovered in 1976. Though too many lives were lost during this outbreak, it resulted in the significantly accelerated clinical development of a number of candidate vaccines through an extraordinary collaborative global effort coordinated by the World Health Organisation (WHO) and involving a number of companies, trial centres, funders, global stakeholders and agencies. We have acquired substantial safety and immunogenicity data on a number of vaccines in Caucasian and African populations. The rapid pace of events led to the initiation of the landmark efficacy trial testing the rVSV-vectored vaccine, which showed high level efficacy in an outbreak setting when deployed using an innovative ring vaccination strategy. Though the Public Health Emergency of International Concern (PHEIC) declared by the WHO has now been lifted, the global scientific community faces numerous challenges ahead to ensure that there is a licensed, deployable vaccine available for use in future outbreaks for at least the Zaire and Sudan strains of Ebola virus. There remain several unanswered questions on the durability of protection, mechanistic immunological correlates and preferred deployment strategies. This review outlines a brief history of the development of Ebola vaccines, the significant progress made since the scale of the outbreak became apparent, some lessons learnt and how they could shape future development of vaccines and the management of similar outbreaks. Copyright © 2017. Published by Elsevier Ltd.

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

PubMed Central

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

2013-01-01

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

[Pneumococcal vaccine: protection of adults and reduction of antibiotic resistence by vaccination of children with a conjugated vaccine].

PubMed

Pletz, Mathias W

2011-06-01

Pneumococcal infections (pneumonia, otitis media, sinusitis, meningitis) are common and usually involve toddlers, immunocompromised and the elderly. Main reservoir of pneumococci is the nasopharyngeal zone of healthy carriers, especially of toddlers. Currently, two types of pneumococcal vaccines are in clinical use, which induce production of antibodies against capsular polysaccharides. The older vaccine consists of pure capsular polysaccharides. It induces a limited immunity, because polysaccharides are poor antigens that stimulate mainly B-cells. In children under two years of age this vaccine is not used, because it does not induce a sufficient immunologic response, presumably because of the immaturity of their immune system. In 2000, a vaccination program with a novel pneumococcal vaccine was launched in the USA. This vaccine contains capsular polysaccharides, that are conjugated with a highly immunogenic protein. It induces both a T cell and B cell response that results in specific humoral and mucosal immunity. U.S. data demonstrate, that serotypes covered by the conjugated vaccine can be reduced in the whole population by vaccination of children being the main reservoir of pneumococci. This so called ,,herd protection" results in a decrease in invasive pneumococcal diseases in vaccinees and non-vaccinees as well as in a reduction of antibiotic resistance rates by reducing resistant pneumococcal cones.

Public trust in vaccination: an analytical framework.

PubMed

Gopichandran, Vijayaprasad

2017-01-01

While vaccination is one of the most successful public health interventions, there has always been a parallel movement against vaccines. Apart from scientific factors, the uptake of vaccinations is influenced by historical, political, sociocultural and economic factors. In India, the health system is struggling with logistical weaknesses in taking vaccination to the remotest corners; while on the other hand, some people in places where vaccination is available resist it. Unwillingness to be vaccinated is a growing problem in the developed world. This trend is gradually emerging in several parts of India as well. Other factors, such as heightened awareness of the profit motives of the vaccine industry, conflicts of interest among policy-makers, and social, cultural and religious considerations have eroded the people's trust in vaccination. This paper develops an analytical framework to assess trust in vaccination. The framework considers trust in vaccination from four perspectives - trust in the health system, the vaccine policy, vaccination providers and specific vaccines. The framework considers specific issues involved in vaccination trust, including the increasing scepticism towards medical technology, perceptions of conflicts of interest in the vaccine policy, and of lack of transparency and openness, the presence of strong alternative schools of thought, influence of the social media. The paper will conclude by arguing that engaging with communities and having a dialogue about the vaccination policy is an ethical imperative.

Vaccine transport and storage: environmental challenges.

PubMed

Zaffran, M

1996-01-01

This paper describes the current status of the vaccine cold chain that was developed in the 1970s. It then describes the changes that are likely to take place in the next 5 to 10 years and their potential impact on the existing system. For more than 20 years, the cold chain system and vaccine handling rules have been set to the speed of the most fragile of the EPI vaccines namely: Oral Polio Vaccine. This has led to the establishment by WHO of stringent vaccine handling rules and Standard Performance Specifications for cold chain equipment. Major changes are occurring that will impact on immunization programmes: The introduction of Vaccine Vial Monitor (VVM), the prospect of an increase in the stability of OPV and the worldwide ban on refrigeration gases and insulation foaming agents.

Neurological adverse events associated with vaccination.

PubMed

Piyasirisilp, Sucheep; Hemachudha, Thiravat

2002-06-01

Public tolerance to adverse reactions is minimal. Several reporting systems have been established to monitor adverse events following immunization. The present review summarizes data on neurologic complications following vaccination, and provides evidence that indicates whether they were directly associated with the vaccines. These complications include autism (measles vaccine), multiple sclerosis (hepatitis B vaccine), meningoencephalitis (Japanese encephalitis vaccine), Guillain-Barré syndrome and giant cell arteritis (influenza vaccine), and reactions after exposure to animal rabies vaccine. Seizures and hypotonic/hyporesponsive episodes following pertussis vaccination and potential risks associated with varicella vaccination, as well as vaccine-associated paralytic poliomyelitis following oral poliovirus vaccination, are also described. In addition, claims that complications are caused by adjuvants, preservatives and contaminants [i.e. macrophagic myofasciitis (aluminium), neurotoxicity (thimerosal), and new variant Creutzfeldt-Jakob disease (bovine-derived materials)] are discussed.

Potential of polymeric particles as future vaccine delivery systems/adjuvants for parenteral and non-parenteral immunization against tuberculosis: A systematic review.

PubMed

Khademi, Farzad; Derakhshan, Mohammad; Yousefi-Avarvand, Arshid; Tafaghodi, Mohsen

2018-02-01

Production of effective tuberculosis (TB) vaccine is necessity. However, the development of new subunit vaccines is faced with concerns about their weak immunogenicity. To overcome such problems, polymers-based vaccine delivery systems have been proposed to be used via various routes. The purpose of this study was to determine the potential of polymeric particles as future vaccine delivery systems/adjuvants for parenteral and non-parenteral immunization against TB. PubMed, Scopus, Science-Direct, and the ISI web of knowledge databases were searched for related keywords. A total of 420 articles, written up to June 25, 2016, were collected on the potential of polymeric particles as TB vaccine delivery systems after parenteral and non-parenteral immunization. Thirty-one relevant articles were selected by applying inclusion and exclusion criteria. It was shown that the immunogenicity of TB vaccines had been improved by using biodegradable and non-biodegradable synthetic polymers as well as natural polymers and they are better able to enhance the humoral and cellular immune responses, compared to TB vaccines alone. The present study revealed that various polymeric particles, after M. tuberculosis challenge in animal models, provide long-lasting protection against TB. PLGA (poly (lactide-co-glycolide)) and chitosan polymers were widely used as TB vaccine delivery systems/adjuvants. It seems that PLGA and chitosan polymers are well-suited particles for the parenteral and non-parenteral administration of TB vaccines, respectively. Non-biodegradable synthetic polymers in comparison with biodegradable synthetic and natural polymers have been used less frequently. Therefore, further study on this category of polymers is required.

European union regulatory developments for new vaccine adjuvants and delivery systems.

PubMed

Sesardic, Dorothea; Dobbelaer, Roland

2004-06-23

Interest in vaccine adjuvants and new delivery systems has grown rapidly over the past few years. New vaccine candidates have emerged, which, because of their poor immunogenicity, rely on adjuvants to improve their presentation and targeting and to potentiate their protective immune response. Better understandings of the mechanisms of action, together with logistic and economical considerations have resulted in an explosion of technologies. However, there have been few new registered products for human use, and antigens incorporated into immunostimulating reconstituted influenza virosomes have only relatively recently been licensed in European Union (EU) countries. Influenza vaccine, adjuvanted with water in oil emulsion containing squalene (adjuvant MF59C1) is now also approved. Although current EU regulations focus on traditional adjuvants, notably aluminium and calcium salts, advances have been made in regulatory considerations. The European agency for the evaluation of medicinal products, through its working parties, is actively drafting guidance on requirements for the evaluation of new adjuvants in vaccines. This paper summarises the new developments in EU regulatory aspects relevant to adjuvant quality at development stages, during the manufacturing process, and at the final bulk stage of adjuvant with antigen, and also summarises regulatory expectation regarding safety at pre-clinical and clinical stages. The paper highlights the regulatory concerns and existing bottlenecks that have led to slow approval of new technologies.

Childhood vaccination: achievements and challenges.

PubMed

Ndumbe, P

1996-09-01

As the goal of eradicating smallpox was being met, the World Health Organization created its Expanded Programme on Immunisation (EPI) in 1974 and reached its initial goal of achieving full vaccination of 80% of the world's children by 1990. This effort was aided by the creation of "cold chain" delivery systems and resulted in the annual saving of 3.5 million children in less-developed countries. Current EPI vaccination goals include 1) eradication of poliomyelitis by the year 2000, 2) elimination of neonatal tetanus by the year 1995, 3) control of measles and hepatitis B, and 4) immunization of 90% of the world's children 1 year or younger by the year 2000. Goals of the Children's Vaccine Initiative (formed in 1991) include 1) provision of an adequate supply of affordable, safe, and effective vaccines; 2) production of improved and new vaccines; and 3) simplification of the logistics of vaccine delivery. Future challenges are to sustain high vaccination coverage, reach the unreached, achieve proper storage of vaccines and reduce waste, integrate new vaccines into national programs, and achieve vaccine self-sufficiency. The fact that these challenges will be difficult to achieve is illustrated by the situation in Africa where the high immunization levels achieved in 1990 have dropped dramatically. Those who must act to implement immunization programs are health personnel, families, governments, and development partners. In order to achieve equity in health, every child must be reached, governments must be made accountable for programs, health workers must convince families of the importance of vaccination, delivery systems must be in place to take advantage of the new vaccines being delivered, and a multisectoral approach must be taken to assure sustainability.

Vaccine Effects on Heterogeneity in Susceptibility and Implications for Population Health Management.

PubMed

Langwig, Kate E; Wargo, Andrew R; Jones, Darbi R; Viss, Jessie R; Rutan, Barbara J; Egan, Nicholas A; Sá-Guimarães, Pedro; Kim, Min Sun; Kurath, Gael; Gomes, M Gabriela M; Lipsitch, Marc

2017-11-21

Heterogeneity in host susceptibility is a key determinant of infectious disease dynamics but is rarely accounted for in assessment of disease control measures. Understanding how susceptibility is distributed in populations, and how control measures change this distribution, is integral to predicting the course of epidemics with and without interventions. Using multiple experimental and modeling approaches, we show that rainbow trout have relatively homogeneous susceptibility to infection with infectious hematopoietic necrosis virus and that vaccination increases heterogeneity in susceptibility in a nearly all-or-nothing fashion. In a simple transmission model with an R 0 of 2, the highly heterogeneous vaccine protection would cause a 35 percentage-point reduction in outbreak size over an intervention inducing homogenous protection at the same mean level. More broadly, these findings provide validation of methodology that can help to reduce biases in predictions of vaccine impact in natural settings and provide insight into how vaccination shapes population susceptibility. IMPORTANCE Differences among individuals influence transmission and spread of infectious diseases as well as the effectiveness of control measures. Control measures, such as vaccines, may provide leaky protection, protecting all hosts to an identical degree, or all-or-nothing protection, protecting some hosts completely while leaving others completely unprotected. This distinction can have a dramatic influence on disease dynamics, yet this distribution of protection is frequently unaccounted for in epidemiological models and estimates of vaccine efficacy. Here, we apply new methodology to experimentally examine host heterogeneity in susceptibility and mode of vaccine action as distinct components influencing disease outcome. Through multiple experiments and new modeling approaches, we show that the distribution of vaccine effects can be robustly estimated. These results offer new experimental and

Public trust and vaccine acceptance-international perspectives

PubMed Central

Ozawa, Sachiko; Stack, Meghan L

2013-01-01

Vaccines save millions of lives every year. They are one of the safest and most effective public health interventions in keeping populations healthy while bringing numerous social and economic benefits. Vaccines play an important role in ensuring that children, regardless of where they live, can have a healthy start to life. New financing mechanisms that allow poorer countries to gain access to vaccines faster than ever mean additional deaths and disabilities are projected to be saved during the Decade of Vaccines (2011–2020). Trust in vaccines and in the health system is an important element of public health programs that aim to deliver life-saving vaccines. Indeed, understanding the contributors and threats to trust is essential to explaining vaccine acceptance, particularly as they vary across epidemiologic conditions, specific vaccines and cultural and sociopolitical settings. Greater efforts to communicate the benefits and risks of vaccines and address issues with evidence-based information will help improve and sustain public trust in vaccines and health systems worldwide. Measuring and monitoring trust levels and focusing on deliberate efforts to build trust in vaccines are important steps to reducing vaccine confidence gaps when they occur. PMID:23733039

Tricomponent Immunopotentiating System as a Novel Molecular Design Strategy for Malaria Vaccine Development ▿

PubMed Central

Miyata, Takeshi; Harakuni, Tetsuya; Tsuboi, Takafumi; Sattabongkot, Jetsumon; Ikehara, Ayumu; Tachibana, Mayumi; Torii, Motomi; Matsuzaki, Goro; Arakawa, Takeshi

2011-01-01

The creation of subunit vaccines to prevent malaria infection has been hampered by the intrinsically weak immunogenicity of the recombinant antigens. We have developed a novel strategy to increase immune responses by creating genetic fusion proteins to target specific antigen-presenting cells (APCs). The fusion complex was composed of three physically linked molecular entities: (i) a vaccine antigen, (ii) a multimeric α-helical coiled-coil core, and (iii) an APC-targeting ligand linked to the core via a flexible linker. The vaccine efficacy of the tricomponent complex was evaluated using an ookinete surface protein of Plasmodium vivax, Pvs25, and merozoite surface protein-1 of Plasmodium yoelii. Immunization of mice with the tricomponent complex induced a robust antibody response and conferred substantial levels of P. vivax transmission blockade as evaluated by a membrane feed assay, as well as protection from lethal P. yoelii infection. The observed effect was strongly dependent on the presence of all three components physically integrated as a fusion complex. This system, designated the tricomponent immunopotentiating system (TIPS), onto which any recombinant protein antigens or nonproteinaceous substances could be loaded, may be a promising strategy for devising subunit vaccines or adjuvants against various infectious diseases, including malaria. PMID:21807905

Nursing case management, peer coaching, and hepatitis a and B vaccine completion among homeless men recently released on parole: randomized clinical trial.

PubMed

Nyamathi, Adeline; Salem, Benissa E; Zhang, Sheldon; Farabee, David; Hall, Betsy; Khalilifard, Farinaz; Leake, Barbara

2015-01-01

Although hepatitis A virus (HAV) and hepatitis B virus (HBV) infections are vaccine-preventable diseases, few homeless parolees coming out of prisons and jails have received the hepatitis A and B vaccination series. The study focused on completion of the HAV and HBV vaccine series among homeless men on parole. The efficacy of three levels of peer coaching (PC) and nurse-delivered interventions was compared at 12-month follow-up: (a) intensive peer coaching and nurse case management (PC-NCM); (b) intensive PC intervention condition, with minimal nurse involvement; and (c) usual care (UC) intervention condition, which included minimal PC and nurse involvement. Furthermore, we assessed predictors of vaccine completion among this targeted sample. A randomized control trial was conducted with 600 recently paroled men to assess the impact of the three intervention conditions (PC-NCM vs. PC vs. UC) on reducing drug use and recidivism; of these, 345 seronegative, vaccine-eligible subjects were included in this analysis of completion of the Twinrix HAV/HBV vaccine. Logistic regression was added to assess predictors of completion of the HAV/HBV vaccine series and chi-square analysis to compare completion rates across the three levels of intervention. Vaccine completion rate for the intervention conditions were 75.4% (PC-NCM), 71.8% (PC), and 71.9% (UC; p = .78). Predictors of vaccine noncompletion included being Asian and Pacific Islander, experiencing high levels of hostility, positive social support, reporting a history of injection drug use, being released early from California prisons, and being admitted for psychiatric illness. Predictors of vaccine series completion included reporting having six or more friends, recent cocaine use, and staying in drug treatment for at least 90 days. Findings allow greater understanding of factors affecting vaccination completion in order to design more effective programs among the high-risk population of men recently released from

Seropositivity to non-vaccine incorporated genotypes induced by the bivalent and quadrivalent HPV vaccines: A systematic review and meta-analysis.

PubMed

Bissett, Sara L; Godi, Anna; Jit, Mark; Beddows, Simon

2017-07-13

Human papillomavirus vaccines have demonstrated remarkable efficacy against persistent infection and disease associated with vaccine-incorporated genotypes and a degree of efficacy against some genetically related, non-vaccine-incorporated genotypes. The vaccines differ in the extent of cross-protection against these non-vaccine genotypes. Data supporting the role for neutralizing antibodies as a correlate or surrogate of cross-protection are lacking, as is a robust assessment of the seroconversion rates against these non-vaccine genotypes. We performed a systematic review and meta-analysis of available data on vaccine-induced neutralizing antibody seropositivity to non-vaccine incorporated HPV genotypes. Of 304 articles screened, 9 were included in the analysis representing ca. 700 individuals. The pooled estimate for seropositivity against HPV31 for the bivalent vaccine (86%; 95%CI 78-91%) was higher than that for the quadrivalent vaccine (61%; 39-79%; p=0.011). The pooled estimate for seropositivity against HPV45 for the bivalent vaccine (50%; 37-64%) was also higher than that for the quadrivalent vaccine (16%; 6-36%; p=0.007). Seropositivity against HPV33, HPV52 and HPV58 were similar between the vaccines. Mean seropositivity rates across non-vaccine genotypes were positively associated with the corresponding vaccine efficacy data reported from vaccine trials. These data improve our understanding of vaccine-induced functional antibody specificity against non-vaccine incorporated genotypes and may help to parameterize vaccine-impact models and improve patient management in a post-vaccine setting. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

A Promising IFN-Deficient System to Manufacture IFN-Sensitive Influenza Vaccine Virus.

PubMed

Chen, Can; Fan, Wenhui; Li, Jing; Zheng, Weinan; Zhang, Shuang; Yang, Limin; Liu, Di; Liu, Wenjun; Sun, Lei

2018-01-01

Interferon (IFN)-sensitive and replication-incompetent influenza viruses are likely to be the alternatives to inactivated and attenuated virus vaccines. Some IFN-sensitive influenza vaccine candidates with modified non-structural protein 1 (NS1) are highly attenuated in IFN-competent hosts but induce robust antiviral immune responses. However, little research has been done on the manufacturability of these IFN-sensitive vaccine viruses. Here, RIG-I-knockout 293T cells were used to package the IFN-sensitive influenza A/WSN/33 (H1N1) virus expressing the mutant NS1 R38A/K41A. We found that the packaging efficiency of the NS1 R38A/K41A virus in RIG-I-knockout 293T cells was much higher than that in 293T cells. Moreover, the NS1 R38A/K41A virus almost lost its IFN antagonist activity and could no longer replicate in A549, MDCK, and Vero cells after 3-6 passages. This indicated that the replication of NS1 R38A/K41A virus is limited in conventional cells. Therefore, we further established a stable Vero cell line expressing the wild-type (WT) NS1 of the WSN virus, based on the Tet-On 3G system. The NS1 R38A/K41A virus was able to steadily propagate in this IFN-deficient cell line for at least 20 passages. In a mouse model, the NS1 R38A/K41A virus showed more than a 4-log reduction in lung virus titers compared to the WT virus at 3 and 5 days post infection. Furthermore, we observed that the NS1 R38A/K41A virus triggered high-level of IFN-α/β production in lung tissues and was eliminated from the host in a relatively short period of time. Additionally, this virus induced high-titer neutralizing antibodies against the WT WSN, A/Puerto Rico/8/1934 (PR8), or A/California/04/2009 (CA04) viruses and provided 100% protection against the WT WSN virus. Thus, we found that the replication of the NS1 R38A/K41A virus was limited in IFN-competent cells and mice. We also presented a promising IFN-deficient system, involving a RIG-I-knockout 293T cell line to package the IFN

The comprehensive 'Communicate to Vaccinate' taxonomy of communication interventions for childhood vaccination in routine and campaign contexts.

PubMed

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

2017-05-10

Communication can be used to generate demand for vaccination or address vaccine hesitancy, and is crucial to successful childhood vaccination programmes. Research efforts have primarily focused on communication for routine vaccination. However, vaccination campaigns, particularly in low- or middle-income countries (LMICs), also use communication in diverse ways. Without a comprehensive framework integrating communication interventions from routine and campaign contexts, it is not possible to conceptualise the full range of possible vaccination communication interventions. Therefore, vaccine programme managers may be unaware of potential communication options and researchers may not focus on building evidence for interventions used in practice. In this paper, we broaden the scope of our existing taxonomy of communication interventions for routine vaccination to include communication used in campaigns, and integrate these into a comprehensive taxonomy of vaccination communication interventions. Building on our taxonomy of communication for routine vaccination, we identified communication interventions used in vaccination campaigns through a targeted literature search; observation of vaccination activities in Cameroon, Mozambique and Nigeria; and stakeholder consultations. We added these interventions to descriptions of routine vaccination communication and categorised the interventions according to their intended purposes, building from an earlier taxonomy of communication related to routine vaccination. The comprehensive taxonomy groups communication used in campaigns and routine childhood vaccination into seven purpose categories: 'Inform or Educate'; 'Remind or Recall'; 'Enhance Community Ownership'; 'Teach Skills'; 'Provide Support'; 'Facilitate Decision Making' and 'Enable Communication'. Consultations with LMIC stakeholders and experts informed the taxonomy's definitions and structure and established its potential uses. This taxonomy provides a standardised way

Understanding dengue pathogenesis: implications for vaccine design.

PubMed Central

Stephenson, John R.

2005-01-01

In the second half of the twentieth century dengue spread throughout the tropics, threatening the health of a third of the world's population. Dengue viruses cause 50-100 million cases of acute febrile disease every year, including more than 500,000 reported cases of the severe forms of the disease--dengue haemorrhagic fever and dengue shock syndrome. Attempts to create conventional vaccines have been hampered by the lack of suitable experimental models, the need to provide protection against all four serotypes simultaneously and the possible involvement of virus-specific immune responses in severe disease. The current understanding of dengue pathogenesis is outlined in this review, with special emphasis on the role of the immune response. The suspected involvement of the immune system in increased disease severity and vascular damage has raised concerns about every vaccine design strategy proposed so far. Clearly more research is needed on understanding the correlates of protection and mechanisms of pathogenesis. There is, however, an urgent need to provide a solution to the escalating global public health problems caused by dengue infections. Better disease management, vector control and improved public health measures will help reduce the current disease burden, but a safe and effective vaccine is probably the only long-term solution. Although concerns have been raised about the possible safety and efficacy of both conventional and novel vaccine technologies, the situation is now so acute that it is not possible to wait for the perfect vaccine. Consequently the careful and thorough evaluation of several of the current candidate vaccines may be the best approach to halting the spread of disease. PMID:15868023

Licensure strategy for pre- and post-exposure prophylaxis of biothrax vaccine: the first vaccine licensed using the FDA animal rule.

PubMed

Longstreth, Janice; Skiadopoulos, Mario H; Hopkins, Robert J

2016-12-01

The availability of a licensed anthrax vaccine that is safe, effective, and easy to administer for both pre- and post-exposure prophylaxis is critical to successfully manage and prevent potential anthrax attacks. BioThrax® (Anthrax Vaccine Adsorbed; AVA) is the only licensed anthrax vaccine in the US. Areas covered: Recent licensed improvements to BioThrax vaccine for pre-exposure prophylaxis (PrEP) have included an intramuscular (IM) five-dose schedule (in 2008) and a three-dose IM primary series at 0, 1 and 6 months (in 2012). Post-exposure prophylaxis (PEP) - three doses given subcutaneously (SC) at 0, 2, and 4 weeks - was licensed in 2015. We review the anthrax disease and vaccine literature that supported these licensure efforts. Expert commentary: This PEP licensure is the first time the FDA's Animal Rule has been used to license a vaccine. Additional improvements such as fewer vaccine doses and reduced time to protection are desirable for a PEP vaccine and are being pursued with next generation vaccine candidates.

Vaccine knowledge and practices of primary care providers of exempt vs. vaccinated children

PubMed Central

Salmon, Daniel A.; Pan, William K.Y.; Omer, Saad B.; Navar, Ann Marie; Orenstein, Walter; Marcuse, Edgar K.; Taylor, James; deHart, M. Patricia; Stokley, Shannon; Carter, Terrell; Halsey, Neal A.

2014-01-01

Objectives: Compare vaccine knowledge, attitudes and practices of primary care providers for fully vaccinated children and children who are exempt from school immunization requirements. Methods: We conducted a mailed survey of parent-identified primary care providers from four states to measure perceived risks and benefits of vaccination and other key immunization beliefs. Frequencies of responses were stratified by type of provider, identified by exempt versus vaccinated children. Logistic regression was used to calculate odds ratios for responses by provider type. Results: 551 surveys were completed (84.3% response rate). Providers for exempt children had similar attitudes to providers for non-exempt children. However, there were statistically significant increased concerns among providers for exempt children regarding vaccine safety and lack of perceived individual and community benefits for vaccines compared to other providers. Conclusions: The great majority of providers for exempt children had similar attitudes about vaccine safety, effectiveness and benefits as providers of non-exempt children. Although providers for exempt children were more likely to believe that multiple vaccines weaken a child’s immune system and were concerned about vaccine safety and less likely to consider vaccines were beneficial, a substantial proportion of providers of both exempt and vaccinated children have concerns about vaccine safety and believe that CDC underestimates the frequency of vaccine side effects. Effective continuing education of providers about the risks and benefits of immunization and including in vaccine recommendations more information on pre and post licensing vaccine safety evaluations may help address these concerns. PMID:18424918

Role of parasitic vaccines in integrated control of parasitic diseases in livestock

PubMed Central

Sharma, Neelu; Singh, Veer; Shyma, K. P.

2015-01-01

Parasitic infections adversely affect animal’s health and threaten profitable animal production, thus affecting the economy of our country. These infections also play a major role in the spread of zoonotic diseases. Parasitic infections cause severe morbidity and mortality in animals especially those affecting the gastrointestinal system and thus affect the economy of livestock owner by decreasing the ability of the farmer to produce economically useful animal products. Due to all these reasons proper control of parasitic infection is critically important for sustained animal production. The most common and regularly used method to control parasitic infection is chemotherapy, which is very effective but has several disadvantages like drug resistance and drug residues. Integrated approaches to control parasitic infections should be formulated including grazing management, biological control, genetic resistance of hosts, and parasitic vaccines. India ranks first in cattle and buffalo population, but the majority of livestock owners have fewer herds, so other measures like grazing management, biological control, genetic resistance of hosts are not much practical to use. The most sustainable and economical approach to control parasitic infection in our country is to vaccinate animals, although vaccines increase the initial cost, but the immunity offered by the vaccine are long lived. Thus, vaccination of animals for various clinical, chronic, subclinical parasitic infections will be a cheaper and effective alternative to control parasitic infection for long time and improve animal production. PMID:27047140

Vaccines. An Ebola whole-virus vaccine is protective in nonhuman primates.

PubMed

Marzi, Andrea; Halfmann, Peter; Hill-Batorski, Lindsay; Feldmann, Friederike; Shupert, W Lesley; Neumann, Gabriele; Feldmann, Heinz; Kawaoka, Yoshihiro

2015-04-24

Zaire ebolavirus is the causative agent of the current outbreak of hemorrhagic fever disease in West Africa. Previously, we showed that a whole Ebola virus (EBOV) vaccine based on a replication-defective EBOV (EBOVΔVP30) protects immunized mice and guinea pigs against lethal challenge with rodent-adapted EBOV. Here, we demonstrate that EBOVΔVP30 protects nonhuman primates against lethal infection with EBOV. Although EBOVΔVP30 is replication-incompetent, we additionally inactivated the vaccine with hydrogen peroxide; the chemically inactivated vaccine remained antigenic and protective in nonhuman primates. EBOVΔVP30 thus represents a safe, efficacious, whole-EBOV vaccine candidate that differs from other EBOV vaccine platforms in that it presents all viral proteins and the viral RNA to the host immune system, which might contribute to protective immune responses. Copyright © 2015, American Association for the Advancement of Science.

Live-attenuated tetravalent dengue vaccines: The needs and challenges of post-licensure evaluation of vaccine safety and effectiveness.

PubMed

Wichmann, Ole; Vannice, Kirsten; Asturias, Edwin J; de Albuquerque Luna, Expedito José; Longini, Ira; Lopez, Anna Lena; Smith, Peter G; Tissera, Hasitha; Yoon, In-Kyu; Hombach, Joachim

2017-10-09

Since December 2015, the first dengue vaccine has been licensed in several Asian and Latin American countries for protection against disease from all four dengue virus serotypes. While the vaccine demonstrated an overall good safety and efficacy profile in clinical trials, some key research questions remain which make risk-benefit-assessment for some populations difficult. As for any new vaccine, several questions, such as very rare adverse events following immunization, duration of vaccine-induced protection and effectiveness when used in public health programs, will be addressed by post-licensure studies and by data from national surveillance systems after the vaccine has been introduced. However, the complexity of dengue epidemiology, pathogenesis and population immunity, as well as some characteristics of the currently licensed vaccine, and potentially also future, live-attenuated dengue vaccines, poses a challenge for evaluation through existing monitoring systems, especially in low and middle-income countries. Most notable are the different efficacies of the currently licensed vaccine by dengue serostatus at time of first vaccination and by dengue virus serotype, as well as the increased risk of dengue hospitalization among young vaccinated children observed three years after the start of vaccination in one of the trials. Currently, it is unknown if the last phenomenon is restricted to younger ages or could affect also seronegative individuals aged 9years and older, who are included in the group for whom the vaccine has been licensed. In this paper, we summarize scientific and methodological considerations for public health surveillance and targeted post-licensure studies to address some key research questions related to live-attenuated dengue vaccines. Countries intending to introduce a dengue vaccine should assess their capacities to monitor and evaluate the vaccine's effectiveness and safety and, where appropriate and possible, enhance their surveillance