Publics and vaccinomics: beyond public understanding of science

Vaccines have been among the most effective tools for addressing global public health challenges. With the advent of genomics, novel approaches for vaccine discovery are opening up new opportunities for vaccine development and applications, particularly with the expectation of personalized vaccines and the possibility of addressing a broader range of infectious diseases. In this context, it is useful to reflect on the social contexts of vaccine development as these have been influenced by social, ethical, political challenges. This article discusses the historical context of vaccine controversies and factors that help explain public acceptance and resistance, illustrating that these challenges go well beyond simple public misunderstandings. The broader vaccine challenges evident along the innovation trajectory, from development to commercialization and implementation include problems in research and development, organizational issues, and legal and regulatory challenges that may collectively contribute to public resistance or confidence. The recent history of genomics provides further lessons that the developing field of vaccinomics can learn from.     

Diagnostic testing for vaccinomics: is the regulatory approval framework adequate? A comparison of Canada, the United States, and Europe

Vaccinomics aims to integrate variability information from multiple levels of the biological hierarchy from genome to proteome to metabolome, and ways in which these biological parts interact with each other and the environment. Vaccinomics holds significant promise as a new public health tool in designing safer and more effective vaccines for both developed and developing countries. Vaccinomics tests that are envisioned to be used in tandem with vaccine-based health interventions could permit an informed forecast of individual and subpopulation variations in immune responses to vaccines, reduce adverse effects, and contribute to a foundation for rational and directed use of vaccines. A proactive, multidisciplinary engagement with vaccinomics is now timely and much needed in order to develop regulations that best ensure the protection of the public and promote the transition of vaccinomics innovations from discovery to real-life public health applications. This article examines and compares the regulatory oversight of vaccinomics tests in Canada, the United States, and Europe. Recent trends in these jurisdictions suggest that regulatory agencies view personalized genomics/omics medicine, such as vaccinomics, as a desirable goal. At the same time, proposals to increase oversight could impact progress in the field and affect the availability of vaccinomics tests in public health practice and the diagnostic test market. The comparative analysis of vaccinomics in three jurisdictions presented in this article highlights both the convergence and divergence of regulatory oversight. In a rapidly emerging field such as vaccinomics that is pivotal for global public health, achieving better harmonization of policies may be an advantageous target, while ensuring that symmetry exists between the goals of public safety and promoting public health innovation. We suggest it is now timely to proactively initiate a constructive dialogue among all stakeholders (publics, policymakers, researchers, private sector, governments) to foster the development of appropriately targeted regulatory policies in this field.     

Vaccinomics and a new paradigm for the development of preventive vaccines against viral infections

In this article we define vaccinomics as the integration of immunogenetics and immunogenomics with systems biology and immune profiling. Vaccinomics is based on the use of cutting edge, high-dimensional (so called "omics") assays and novel bioinformatics approaches to the development of next-generation vaccines and the expansion of our capabilities in individualized medicine. Vaccinomics will allow us to move beyond the empiric "isolate, inactivate, and inject" approach characterizing past vaccine development efforts, and toward a more detailed molecular and systemic understanding of the carefully choreographed series of biological processes involved in developing viral vaccine-induced "immunity." This enhanced understanding will then be applied to overcome the obstacles to the creation of effective vaccines to protect against pathogens, particularly hypervariable viruses, with the greatest current impact on public health. Here we provide an overview of how vaccinomics will inform vaccine science, the development of new vaccines and/or clinically relevant biomarkers or surrogates of protection, vaccine response heterogeneity, and our understanding of immunosenescence.     

Steering vaccinomics innovations with anticipatory governance and participatory foresight

Vaccinomics is the convergence of vaccinology and population-based omics sciences. The success of knowledge-based innovations such as vaccinomics is not only contingent on access to new biotechnologies. It also requires new ways of governance of science, knowledge production, and management. This article presents a conceptual analysis of the anticipatory and adaptive approaches that are crucial for the responsible design and sustainable transition of vaccinomics to public health practice. Anticipatory governance is a new approach to manage the uncertainties embedded on an innovation trajectory with participatory foresight, in order to devise governance instruments for collective "steering" of science and technology. As a contrast to hitherto narrowly framed "downstream impact assessments" for emerging technologies, anticipatory governance adopts a broader and interventionist approach that recognizes the social construction of technology design and innovation. It includes in its process explicit mechanisms to understand the factors upstream to the innovation trajectory such as deliberation and cocultivation of the aims, motives, funding, design, and direction of science and technology, both by experts and publics. This upstream shift from a consumer "product uptake" focus to "participatory technology design" on the innovation trajectory is an appropriately radical and necessary departure in the field of technology assessment, especially given that considerable public funds are dedicated to innovations. Recent examples of demands by research funding agencies to anticipate the broad impacts of proposed research--at a very upstream stage at the time of research funding application--suggest that anticipatory governance with foresight may be one way how postgenomics scientific practice might transform in the future toward responsible innovation. Moreover, the present context of knowledge production in vaccinomics is such that policy making for vaccines of the 21st century is occurring in the face of uncertainties where the "facts are uncertain, values in dispute, stakes high and decisions urgent and where no single one of these dimensions can be managed in isolation from the rest." This article concludes, however, that uncertainty is not an accident of the scientific method, but its very substance. Anticipatory governance with participatory foresight offers a mechanism to respond to such inherent sociotechnical uncertainties in the emerging field of vaccinomics by making the coproduction of scientific knowledge by technology and the social systems explicit. Ultimately, this serves to integrate scientific and social knowledge thereby steering innovations to coproduce results and outputs that are socially robust and context sensitive.     

Designing the next generation of vaccines for global public health

Vaccine research and development are experiencing a renaissance of interest from the global scientific community. There are four major reasons for this: (1) the lack of efficacious treatment for many devastating infections; (2) the emergence of multidrug resistant bacteria; (3) the need for improving the safety of the more traditional licensed vaccines; and finally, (4) the great promise for innovative vaccine design and research with convergence of omics sciences, such as genomics, proteomics, immunomics, and vaccinology. Our first project based on omics was initiated in 2000 and was termed reverse vaccinology. At that time, antigen identification was mainly based on bioinformatic analysis of a singular genome. Since then, omics-guided approaches have been applied to its full potential in several proof-of-concept studies in the industry, with the first reverse vaccinology-derived vaccine now in late stage clinical trials and several vaccines developed by omics in preclinical studies. In the meantime, vaccine discovery and development has been further improved with the support of proteomics, functional genomics, comparative genomics, structural biology, and most recently vaccinomics. We illustrate in this review how omics biotechnologies and integrative biology are expected to accelerate the identification of vaccine candidates against difficult pathogens for which traditional vaccine development has thus far been failing, and how research will provide safer vaccines and improved formulations for immunocompromised patients in the near future. Finally, we present a discussion to situate omics-guided rational vaccine design in the broader context of global public health and how it can benefit citizens in both developed and developing countries.     

The top five "game changers" in vaccinology: toward rational and directed vaccine development

Despite the tremendous success of the classical "isolate, inactivate, and inject" approach to vaccine development, new breakthroughs in vaccine research are increasingly reliant on novel approaches that incorporate cutting edge technology and advances in innate and adaptive immunology, microbiology, virology, pathogen biology, genetics, bioinformatics, and many other disciplines in order to: (1) deepen our understanding of the key biological processes that lead to protective immunity, (2) observe vaccine responses on a global, systems level, and (3) directly apply the new knowledge gained to the development of next-generation vaccines with improved safety profiles, enhanced efficacy, and even targeted utility in select populations. Here we highlight five key components foundational to vaccinomics efforts: applied immunogenomics, next generation sequencing and other cutting-edge "omics" technologies, advanced bioinformatics and analysis techniques, and finally, systems biology applied to immune profiling and vaccine responses. We believe these "game changers" will play a critical role in moving us toward the rational and directed development of new vaccines in the 21st century.     

Development of health biotechnology in developing countries: Can private-sector players be the prime movers?

Health biotechnology has rapidly become vital in helping healthcare systems meet the needs of the poor in developing countries. This key industry also generates revenue and creates employment opportunities in these countries. To successfully develop biotechnology industries in developing nations, it is critical to understand and improve the system of health innovation, as well as the role of each innovative sector and the linkages between the sectors. Countries' science and technology capacities can be strengthened only if there are non-linear linkages and strong interrelations among players throughout the innovation process; these relationships generate and transfer knowledge related to commercialization of the innovative health products. The private sector is one of the main actors in healthcare innovation, contributing significantly to the development of health biotechnology via knowledge, expertise, resources and relationships to translate basic research and development into new commercial products and innovative processes. The role of the private sector has been increasingly recognized and emphasized by governments, agencies and international organizations. Many partnerships between the public and private sector have been established to leverage the potential of the private sector to produce more affordable healthcare products. Several developing countries that have been actively involved in health biotechnology are becoming the main players in this industry. The aim of this paper is to discuss the role of the private sector in health biotechnology development and to study its impact on health and economic growth through case studies in South Korea, India and Brazil. The paper also discussed the approaches by which the private sector can improve the health and economic status of the poor.     

Plant-made vaccines in support of the Millennium Development Goals

Vaccines are one of the most successful public health achievements of the last century. Systematic immunisation programs have reduced the burden of infectious diseases on a global scale. However, there are limitations to the current technology, which often requires costly infrastructure and long lead times for production. Furthermore, the requirement to keep vaccines within the cold-chain throughout manufacture, transport and storage is often impractical and prohibitively expensive in developing countries—the very regions where vaccines are most needed. In contrast, plant-made vaccines (PMVs) can be produced at a lower cost using basic greenhouse agricultural methods, and do not need to be kept within such narrow temperature ranges. This increases the feasibility of developing countries producing vaccines locally at a small-scale to target the specific needs of the region. Additionally, the ability of plant-production technologies to rapidly produce large quantities of strain-specific vaccine demonstrates their potential use in combating pandemics. PMVs are a proven technology that has the potential to play an important role in increasing global health, both in the context of the 2015 Millennium Development Goals and beyond.     

新型冠状病毒抗原快速检测研发现状及展望*

新型冠状病毒肺炎疫情的全球大流行,对全球公共健康、社会和经济运转造成了重大影响。在药物研发迟滞及疫苗有效性未得到充分验证的情况下,对人群进行大规模的快速筛查,寻找潜在的感染者(尤其是轻症和无症状患者),并进行集中隔离,切断传播途径和保护易感人群是首要的任务。因此对于SARS-CoV-2感染,早期诊断尤为重要。总结现有市场上的新冠病毒抗原快速检测产品,对全球抗原快速检测市场进行分析,概述其研发的动向并展望了我国在新冠抗原检测新方法、新技术方面的自主创新能力。     

Prioritising Healthcare Workers for Ebola Treatment: Treating Those at Greatest Risk to Confer Greatest Benefit

The Ebola epidemic in Western Africa has highlighted issues related to weak health systems, the politics of drug and vaccine development and the need for transparent and ethical criteria for use of scarce local and global resources during public health emergency. In this paper we explore two key themes. First, we argue that independent of any use of experimental drugs or vaccine interventions, simultaneous implementation of proven public health principles, community engagement and culturally sensitive communication are critical as these measures represent the most cost‐effective and fair utilization of available resources. Second, we attempt to clarify the ethical issues related to use of scarce experimental drugs or vaccines and explore in detail the most critical ethical question related to Ebola drug or vaccine distribution in the current outbreak: who among those infected or at risk should be prioritized to receive any new experimental drugs or vaccines? We conclude that healthcare workers should be prioritised for these experimental interventions, for a variety of reasons.     

Prospects for a dengue virus vaccine

The number of cases of severe dengue disease continues to grow in endemic areas of southeast Asia, Central and South America, and other subtropical regions. Children bear the greatest burden of disease, and the development of an effective vaccine remains a global public health priority. A tetravalent vaccine is urgently needed and must be effective against all four dengue virus serotypes, be cost-effective and provide long-term protection. In this Review we discuss the unique immunological concerns in dengue virus vaccine development and the current prospects for the development of an acceptable vaccine, a goal that is likely to be reached in the near future.     

Application of Ethical Principles to Research using Public Health Data in The Global South: Perspectives from Africa

Existing ethics guidelines, influential literature and policies on ethical research generally focus on real‐time data collection from humans. They enforce individual rights and liberties, thereby lowering need for aggregate protections. Although dependable, emerging public health research paradigms like research using public health data (RUPD) raise new challenges to their application. Unlike traditional research, RUPD is population‐based, aligned to public health activities, and often reliant on pre‐collected longitudinal data. These characteristics, when considered in relation to the generally lower protective ethico‐legal frameworks of the Global South, including Africa, highlight ethical gaps. Health and demographic surveillance systems are examples of public health programs that accommodate RUPD in these contexts. We set out to explore the perspectives of professionals with a working knowledge of these systems to determine practical ways of appropriating the foundational principles of health research to advance the ever growing opportunities in RUPD. We present their perspectives and in relation to the literature and our ethical analysis, make context relevant recommendations. We further argue for the development of a framework founded on the discussions and recommendations as a minimum base for achieving optimal ethics for optimal RUPD in the Global South.     

Public vaccine manufacturing capacity in the Latin American and Caribbean region: Current status and perspectives

The vaccine global market is currently growing at a rate of 16.52%. Nowadays the vaccine manufacturing industry is limited in the sense that not all vaccine manufacturers have the capacity to execute all the steps necessary to produce a successful product. The biological variation inherent to vaccine manufacturing and the initial investment required to bring a vaccine to the market are some of the factors that discourage vaccine manufacturing initiatives.Given the current global context in vaccine innovation and production, and the increasing participation of vaccine manufacturers from developing countries in global markets, this paper aims to review vaccine manufacturing capacity in Latin American and Caribbean (LAC) countries with specific focus on trends in national or public sector manufacturing, presenting current challenges and future opportunities for the sector in meeting national and regional (LAC) needs.Despite the overall low vaccine manufacturing capacity reported within the LAC region within this paper, it is considered that the relatively high and concentrated capacity that exists within a number of countries, combined with political commitment of all countries within the Region, can provide the necessary platform for the continued development of capacity in vaccine development and manufacture within LAC.     

Challenges and opportunities for enhancing biotechnology and technology transfer in developing countries

Biotechnological innovation is gaining increased recognition as an important tool for improving global health. The challenge, however, lies in defining the role of technology transfer to develop therapies for diseases prevalent in developing countries. During the past decade, a large disparity emerged between the developed and developing world in accessing affordable medicines because of the pharmaceutical industry's focus on health areas bearing greatest profits. Discussed herein are several mechanisms that provide partial solutions to this challenge. The Office of Technology Transfer of the US National Institutes of Health has increased its technology licensing pertaining to neglected diseases to partners in developing regions. Establishing partnerships through the transfer of technologies and assisting indigenous institutions build R and D capacity may positively impact policies on protection of intellectual property rights and increase multinational company investments in lesser-developed countries. This will most probably result in the development of more accessible therapies for those in need.     

Review of dengue virus and the development of a vaccine

Dengue viral infection has become an increasing global health concern with over two-fifths of the world's population at risk of infection. It is the most rapidly spreading vector borne disease, attributed to changing demographics, urbanization, environment, and global travel. It continues to be a threat in over 100 tropical and sub-tropical countries, affecting predominantly children. Dengue also carries a hefty financial burden on the health care systems in affected areas, as those infected seek care for their symptoms. The search for a suitable vaccine for dengue has been ongoing for the last sixty years, yet any effective treatment or vaccine remains elusive. A vaccine must be protective for all four serotypes of dengue and be cost-effective. Many approaches to developing candidate vaccines have been employed. The candidates include live attenuated tetravalent vaccines, chimeric tetravalent vaccines based on attenuated dengue virus or Yellow Fever 17D, and recombinant DNA vaccines based on flavivirus and non-flavivirus vectors. This review outlines the challenges involved in dengue vaccine development and presents the current stages of proposed vaccine candidate development.     

HEALTH AS FREEDOM: ADDRESSING SOCIAL DETERMINANTS OF GLOBAL HEALTH INEQUITIES THROUGH THE HUMAN RIGHT TO DEVELOPMENT

In spite of vast global improvements in living standards, health, and well-being, the persistence of absolute poverty and its attendant maladies remains an unsettling fact of life for billions around the world and constitutes the primary cause for the failure of developing states to improve the health of their peoples. While economic development in developing countries is necessary to provide for underlying determinants of health – most prominently, poverty reduction and the building of comprehensive primary health systems – inequalities in power within the international economic order and the spread of neoliberal development policy limit the ability of developing states to develop economically and realize public goods for health. With neoliberal development policies impacting entire societies, the collective right to development, as compared with an individual rights-based approach to development, offers a framework by which to restructure this system to realize social determinants of health. The right to development, working through a vector of rights, can address social determinants of health, obligating states and the international community to support public health systems while reducing inequities in health through poverty-reducing economic growth. At an international level, where the ability of states to develop economically and to realize public goods through public health systems is constrained by international financial institutions, the implementation of the right to development enables a restructuring of international institutions and foreign-aid programs, allowing states to enter development debates with a right to cooperation from other states, not simply a cry for charity.     

Medicines for Malaria Venture: sustaining antimalarial drug development

The Medicines for Malaria Venture (MMV) is committed to discovering, developing and delivering new drugs for malaria. Founded in 1999 as a nonprofit organization bringing private sector management methods to bear on a global public health problem, MMV is today recognized as a leader among the public-private partnerships working on diseases for the developing world. Together with its many partners, MMV manages the world's largest malaria research and development portfolio, covering the innovation spectrum from basic drug discovery to late-stage development.     

Bringing together emerging and endemic zoonoses surveillance: shared challenges and a common solution

Early detection of disease outbreaks in human and animal populations is crucial to the effective surveillance of emerging infectious diseases. However, there are marked geographical disparities in capacity for early detection of outbreaks, which limit the effectiveness of global surveillance strategies. Linking surveillance approaches for emerging and neglected endemic zoonoses, with a renewed focus on existing disease problems in developing countries, has the potential to overcome several limitations and to achieve additional health benefits. Poor reporting is a major constraint to the surveillance of both emerging and endemic zoonoses, and several important barriers to reporting can be identified: (i) a lack of tangible benefits when reports are made; (ii) a lack of capacity to enforce regulations; (iii) poor communication among communities, institutions and sectors; and (iv) complexities of the international regulatory environment. Redirecting surveillance efforts to focus on endemic zoonoses in developing countries offers a pragmatic approach that overcomes some of these barriers and provides support in regions where surveillance capacity is currently weakest. In addition, this approach addresses immediate health and development problems, and provides an equitable and sustainable mechanism for building the culture of surveillance and the core capacities that are needed for all zoonotic pathogens, including emerging disease threats.     

Development of a new platform for neglected tropical disease surveillance

An expanded global focus on the control and elimination of neglected tropical diseases (NTDs) has called attention to the need to develop and validate surveillance strategies that are cost effective and can be integrated across diseases. Here, we describe a multiplex tool for the sensitive detection of antibody responses to NTDs as well as vaccine preventable diseases, malaria, and waterborne and zoonotic infections. The assay platform is robust, can be performed with either serum or dried blood spots and can be adapted to local epidemiological conditions and public health priorities. Multiplex assays open the door to conducting routine serosurveillance for NTDs through demographic health surveillance or malaria indicator surveys.