SMART Vaccines Research Articles

Multi-criteria decision analysis to prioritize the introduction of new vaccines in Indonesia by using the framework of the strategic multi-attribute ranking tool for vaccines (SMART vaccines)

ABSTRACT Background: Decision-making processes regarding new vaccine prioritizations are complex. The objective of this study was to prioritize the introduction of new vaccines in Indonesia. Methods: A multi-criteria decision analysis (MCDA) was applied in this study. A preliminary data collection form was developed to collect country-specific data in relation to 30 pre-defined attributes. In particular, an open-ended questionnaire was conducted among targeted respondents from global level, national level and vaccine manufacturers, which were involved in the financial flows of new vaccine procurement in Indonesia. For setting new vaccines priorities, targeted respondents were asked to assign weight on 10 selected criteria. Results: Top 3 attributes with the highest weight from respondents were premature deaths averted per year, incident cases prevented per year, and cost-effectiveness. Applying criteria scores and weight assessment, the result showed that PCV, rotavirus, HPV, and JE would be on the 1st, 2nd, 3rd, and 4th rank for setting new vaccine priority in Indonesia. There was a significant difference score (p value <0.05) between all these vaccines. Conclusions: PCV, rotavirus and HPV vaccines should be more prioritized than JE vaccine. This ranking is in line with the WHO’s priority list, which potentially illustrates the validity and usefulness of our MCDA-approach.

Engineering and characterization of a novel Self Assembling Protein for Toxoplasma peptide vaccine in HLA-A*11:01, HLA-A*02:01 and HLA-B*07:02 transgenic mice

Fighting smart diseases requires smart vaccines. Novel ways to present protective immunogenic peptide epitopes to human immune systems are needed. Herein, we focus on Self Assembling Protein Nanoparticles (SAPNs) as scaffolds/platforms for vaccine delivery that produce strong immune responses against Toxoplasma gondii in HLA supermotif, transgenic mice. Herein, we present a useful platform to present peptides that elicit CD4+, CD8+ T and B cell immune responses in a core architecture, formed by flagellin, administered in combination with TLR4 ligand-emulsion (GLA-SE) adjuvant. We demonstrate protection of HLA-A*11:01, HLA-A*02:01, and HLA-B*07:02 mice against toxoplasmosis by (i) this novel chimeric polypeptide, containing epitopes that elicit CD8+ T cells, CD4+ T helper cells, and IgG2b antibodies, and (ii) adjuvant activation of innate immune TLR4 and TLR5 pathways. HLA-A*11:01, HLA-A*02:01, and HLA-B*07:02q11 transgenic mouse splenocytes with peptides demonstrated predicted genetic restrictions. This creates a new paradigm-shifting vaccine approach to prevent toxoplasmosis, extendable to other diseases.

Improving accountability in vaccine decision-making

ABSTRACTIntroduction: Healthcare decisions, in particular those affecting entire populations, should be evidence-based and taken by decision-makers sharing broad alignment with affected stakeholders. However, criteria, priorities and procedures for decision-making are sometimes non-transparent, frequently vary considerably across equivalent decision-bodies, do not always consider the broader benefits of new health-measures, and therefore do not necessarily adequately represent the relevant stakeholder-spectrum.Areas covered: To address these issues in the context of the evaluation of new vaccines, we have proposed a first baseline set of core evaluation criteria, primarily selected by members of the vaccine research community, and suggested their implementation in vaccine evaluation procedures. In this communication, we review the consequences and utility of stakeholder-centered core considerations to increase transparency in and accountability of decision-making procedures, in general, and of the benefits gained by their inclusion in Multi-Criteria-Decision-Analysis tools, exemplified by SMART Vaccines, specifically.Expert commentary: To increase effectiveness and comparability of health decision outcomes, decision procedures should be properly standardized across equivalent (national) decision bodies. To this end, including stakeholder-centered criteria in decision procedures would significantly increase their transparency and accountability, support international capacity building to improve health, and reduce societal costs and inequity resulting from suboptimal health decision-making.

Informing vaccine decision-making: A strategic multi-attribute ranking tool for vaccines—SMART Vaccines 2.0

SMART Vaccines 2.0 software is being developed to support decision-making among multiple stakeholders in the process of prioritizing investments to optimize the outcomes of vaccine development and deployment. Vaccines and associated vaccination programs are one of the most successful and effective public health interventions to prevent communicable diseases and vaccine researchers are continually working towards expanding targets for communicable and non-communicable diseases through preventive and therapeutic modes. A growing body of evidence on emerging vaccine technologies, trends in disease burden, costs associated with vaccine development and deployment, and benefits derived from disease prevention through vaccination and a range of other factors can inform decision-making and investment in new and improved vaccines and targeted utilization of already existing vaccines. Recognizing that an array of inputs influences these decisions, the strategic multi-attribute ranking method for vaccines (SMART Vaccines 2.0) is in development as a web-based tool—modified from a U.S. Institute of Medicine Committee effort (IOM, 2015)—to highlight data needs and create transparency to facilitate dialogue and information-sharing among decision-makers and to optimize the investment of resources leading to improved health outcomes. Current development efforts of the SMART Vaccines 2.0 framework seek to generate a weighted recommendation on vaccine development or vaccination priorities based on population, disease, economic, and vaccine-specific data in combination with individual preference and weights of user-selected attributes incorporating valuations of health, economics, demographics, public concern, scientific and business, programmatic, and political considerations.Further development of the design and utility of the tool is being carried out by the National Vaccine Program Office of the Department of Health and Human Services and the Fogarty International Center of the National Institutes of Health. We aim to demonstrate the utility of SMART Vaccines 2.0 through the engagement of a community of relevant stakeholders and to identify a limited number of pilot projects to determine explicitly defined attribute preferences and the related data and model requirements that are responsive to user needs and able to improve the use of evidence for vaccine-related decision-making and consequential priorities of vaccination options.

Beyond cost-effectiveness: Using systems analysis for infectious disease preparedness

Until the recent outbreaks, Ebola vaccines ranked low in decision makers’ priority lists based on cost-effectiveness analysis and (or) corporate profitability. Despite a relatively small number of Ebola-related cases and deaths (compared to other causes), Ebola vaccines suddenly leapt to highest priority among international health agencies and vaccine developers. Clearly, earlier cost-effectiveness analyses badly missed some factors affecting real world decisions. Multi-criteria systems analysis can improve evaluation and prioritization of vaccine development and also of many other health policy and investment decisions. Neither cost-effectiveness nor cost-benefit analysis can capture important aspects of problems such as Ebola or the emerging threat of Zika, especially issues of inequality and disparity—issues that dominate the planning of many global health and economic organizations. Cost-benefit analysis requires assumptions about the specific value of life—an idea objectionable to many analysts and policy makers. Additionally, standard cost-effectiveness calculations cannot generally capture effects on people uninfected with Ebola for example, but nevertheless affected through such factors as contagion, herd immunity, and fear of dread disease, reduction of travel and commerce, and even the hope of disease eradication. Using SMART Vaccines, we demonstrate how systems analysis can visibly include important “other factors” and more usefully guide decision making and beneficially alter priority setting processes.

Strategic Planning in Population Health and Public Health Practice: A Call to Action for Higher Education.

Scarce resources, especially in population health and public health practice, underlie the importance of strategic planning. Public health agencies' current planning and priority setting efforts are often narrow, at times opaque, and focused on single metrics such as cost-effectiveness. As demonstrated by SMART Vaccines, a decision support software system developed by the Institute of Medicine and the National Academy of Engineering, new approaches to strategic planning allow the formal incorporation of multiple stakeholder views and multicriteria decision making that surpass even those sophisticated cost-effectiveness analyses widely recommended and used for public health planning. Institutions of higher education can and should respond by building on modern strategic planning tools as they teach their students how to improve population health and public health practice. Strategic planning in population health and public health practice often uses single indicators of success or, when using multiple indicators, provides no mechanism for coherently combining the assessments. Cost-effectiveness analysis, the most complex strategic planning tool commonly applied in public health, uses only a single metric to evaluate programmatic choices, even though other factors often influence actual decisions. Our work employed a multicriteria systems analysis approach--specifically, multiattribute utility theory--to assist in strategic planning and priority setting in a particular area of health care (vaccines), thereby moving beyond the traditional cost-effectiveness analysis approach. (1) Multicriteria systems analysis provides more flexibility, transparency, and clarity in decision support for public health issues compared with cost-effectiveness analysis. (2) More sophisticated systems-level analyses will become increasingly important to public health as disease burdens increase and the resources to deal with them become scarcer. The teaching of strategic planning in public health must be expanded in order to fill a void in the profession's planning capabilities. Public health training should actively incorporate model building, promote the interactive use of software tools, and explore planning approaches that transcend restrictive assumptions of cost-effectiveness analysis. The Strategic Multi-Attribute Ranking Tool for Vaccines (SMART Vaccines), which was recently developed by the Institute of Medicine and the National Academy of Engineering to help prioritize new vaccine development, is a working example of systems analysis as a basis for decision support.

Strategic priority setting for vaccines policy and global health education

Abstract Background Priority setting for new and existing vaccines is a complex but important task. Health outcomes or cost-effectiveness are not the only criteria for priority ranking of vaccine candidates. Real life prioritisation and development of new vaccines invariably involves balancing many programmatic features, including dosage requirements and cost (and their consequences on coverage and efficacy), developmental risk, interface with existing programmes (for example, vaccination schedules and capabilities), focus on special populations, and even the strengthening of homeland security or public health aid. We aimed to develop a software tool to assist in the process of ranking candidate vaccines. Methods SMART Vaccines (Strategic Multi-Attribute Ranking Tool for Vaccines) combines population-specific data about demographics, health burdens, costs of disease treatment, and design attributes of potential new vaccines to support a multi-attribute utility model. The software offers 28 total attributes (plus up to seven user-defined attributes) from which users can select and weight a subset (maximum of 10) to create SMART Scores to rank candidate vaccines. Sensitivity-analysis tools built into SMART Vaccines allow users to specify the most desirable target product profiles for a single disease, or the ranking of candidate vaccines across different diseases. The programme also allows users to add attributes to the model, and to specify the weights given to the seleted set of attributes used in evaluation of vaccine candidates. Findings Preliminary testing with a range of public health organisations and vaccine developers has demonstrated that the concept underlying SMART Vaccines can be expanded for comparisons between public health interventions (treatment versus prevention of disease options), and even to quite different uses such as vaccines for animal health. Interpretation Early uses of SMART Vaccines have demonstrated that the multi-criteria approach not only enhances transparency in public health decision making, but also allows incorporation of many influential factors that remain hidden or unrecognized in more traditional cost-effectiveness analysis. Furthermore, use of SMART Vaccines facilitates decision convergence when stakeholder interests have conflicting priorities. To bolster the further development of SMART Vaccines, we envision a user community with research universities, especially those with strengths in global public health, to act as the software host. Funding US Department of Health and Human Services, National Vaccine Program Office and Fogarty International Center, National Institutes of Health.

Calcium Antagonists: A Ready Prescription for Treating Infectious Diseases?

Emergence of new and medically resistant pathogenic microbes continues to escalate toward worldwide public health, wild habitat, and commercial crop and livestock catastrophes. Attempts at solving this problem with sophisticated modern biotechnologies, such as smart vaccines and microbicidal and microbistatic drugs that precisely target parasitic bacteria, fungi, and protozoa, remain promising without major clinical and industrial successes. However, discovery of a more immediate, broad spectrum prophylaxis beyond conventional epidemiological approaches might take no longer than the time required to fill a prescription at your neighborhood pharmacy. Findings from a growing body of research suggest calcium antagonists, long approved and marketed for various human cardiovascular and neurological indications, may produce safe, efficacious antimicrobial effects. As a general category of drugs, calcium antagonists include compounds that disrupt passage of Ca(2+) molecules across cell membranes and walls, sequestration and mobilization of free intracellular Ca(2+), and downstream binding proteins and sensors of Ca(2+)-dependent regulatory pathways important for proper cell function. Administration of calcium antagonists alone at current therapeutically relevant doses and schedules, or with synergistic compounds and additional antimicrobial medications, figures to enhance host immunoprotection by directly altering pathogen infection sequences, life cycles, homeostasis, antibiotic tolerances, and numerous other infective, survival, and reproductive processes. Short of being miracle drugs, calcium antagonists are welcome old drugs with new tricks capable of controlling some of the most virulent and pervasive global infectious diseases of plants, animals, and humans, including Chagas' disease, malaria, and tuberculosis.

DCs as targets for vaccine design.

The increasingly stringent requirements laid down by regulatory authorities have brought to an end the largely empirical design of vaccines. Vaccines must now be designed rationally, in order that appropriate immune responses are elicited with few or no side effects. The DC plays a pivotal role in determining the type of immune response that ensues following exposure of the host to an Ag. In this review, we identify some of the features and properties of DCs, and how these properties can be exploited in the design of smart vaccines.