Biotechnology and the transformation of vaccine innovation: The case of the hepatitis B vaccines 1968-2000.
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ABSTRACT: 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.
Project description:With the rapidly increasing demand for poultry products and the current challenges facing the poultry industry, the application of biotechnology to enhance poultry production has gained growing significance. Biotechnology encompasses all forms of technology that can be harnessed to improve poultry health and production efficiency. Notably, biotechnology-based approaches have fueled rapid advances in biological research, including (a) genetic manipulation in poultry breeding to improve the growth and egg production traits and disease resistance, (b) rapid identification of infectious agents using DNA-based approaches, (c) inclusion of natural and synthetic feed additives to poultry diets to enhance their nutritional value and maximize feed utilization by birds, and (d) production of biological products such as vaccines and various types of immunostimulants to increase the defensive activity of the immune system against pathogenic infection. Indeed, managing both existing and newly emerging infectious diseases presents a challenge for poultry production. However, recent strides in vaccine technology are demonstrating significant promise for disease prevention and control. This review focuses on the evolving applications of biotechnology aimed at enhancing vaccine immunogenicity, efficacy, stability, and delivery.
Project description:With increasing globalization, infectious diseases are spreading faster than ever before, creating an urgent need for international collaboration. The rise of emerging economies has changed the traditional collaborative landscape and provided opportunities for more diverse models of collaboration involving developing countries, including North-South, South-South and North-South-South partnerships. Here, we discuss how developing countries can partner with other nations to address their shared health problems and to promote innovation. We look specifically at what drives collaborations and at the challenges that exist for them, and we propose actions that can strengthen these partnerships.
Project description:BackgroundFundamental to vaccine development, manufacturing consistency, and product stability is an understanding of the vaccine structure-activity relationship. With the virus-like particle (VLP) approach for recombinant vaccines gaining popularity, there is growing demand for tools that define their key characteristics. We assessed a suite of non-intrusive VLP epitope structure and function characterization tools by application to the Hepatitis B surface antigen (rHBsAg) VLP-based vaccine.MethodologyThe epitope-specific immune reactivity of rHBsAg epitopes to a given monoclonal antibody was monitored by surface plasmon resonance (SPR) and quantitatively analyzed on rHBsAg VLPs in-solution or bound to adjuvant with a competitive enzyme-linked immunosorbent assay (ELISA). The structure of recombinant rHBsAg particles was examined by cryo transmission electron microscopy (cryoTEM) and in-solution atomic force microscopy (AFM).Principal findingsSPR and competitive ELISA determined relative antigenicity in solution, in real time, with rapid turn-around, and without the need of dissolving the particulate aluminum based adjuvant. These methods demonstrated the nature of the clinically relevant epitopes of HBsAg as being responsive to heat and/or redox treatment. In-solution AFM and cryoTEM determined vaccine particle size distribution, shape, and morphology. Redox-treated rHBsAg enabled 3D reconstruction from CryoTEM images--confirming the previously proposed octahedral structure and the established lipid-to-protein ratio of HBsAg particles. Results from these non-intrusive biophysical and immunochemical analyses coalesced into a comprehensive understanding of rHBsAg vaccine epitope structure and function that was important for assuring the desired epitope formation, determinants for vaccine potency, and particle stability during vaccine design, development, and manufacturing.SignificanceTogether, the methods presented here comprise a novel suite of non-intrusive VLP structural and functional characterization tools for recombinant vaccines. Key VLP structural features were defined and epitope-specific antigenicity was quantified while preserving epitope integrity and particle morphology. These tools should facilitate the development of other VLP-based vaccines.
Project description:Viral hepatitis is a serious health problem all over the world. However, the reduction of the morbidity and mortality due to vaccinations against hepatitis A and hepatitis B has been a major component in the overall reduction in vaccine preventable diseases. We will discuss the epidemiology, vaccine development, and post-vaccination effects of the hepatitis A and B virus. In addition, we discuss attempts to provide hepatitis D vaccine for the 350 million individuals infected with hepatitis B globally. Given the lack of a hepatitis C vaccine, the many challenges facing the production of a hepatitis C vaccine will be shown, along with current and former vaccination trials. As there is no current FDA-approved hepatitis E vaccine, we will present vaccination data that is available in the rest of the world. Finally, we will discuss the existing challenges and questions facing future endeavors for each of the hepatitis viruses, with efforts continuing to focus on dramatically reducing the morbidity and mortality associated with these serious infections of the liver.
Project description:Chile has become one of the main global players in seed production for counter-season markets and research purposes. Chile has a key role contributing to the reduction in seed production shortages in the Northern Hemisphere by speeding up the development of new hybrids, cultivars, and genetically modified (GM) organisms. The seeds that Chile produces for export include a considerable amount of GM seeds. Between 2009 and 2018, 1,081 different seed-planting events were undertaken for seed multiplication and/or research purposes. Every single event that had commodity cultivation status in 2018 in at least one country underwent field activities in Chile at least once over the last 10 y. Chile just adopted a regulatory approach for new plant breeding techniques. This type of regulatory approach should contribute to maintaining the status of Chile as a hot spot for future innovation in plant breeding-based biotechnology.
Project description:Malaria vaccine development entered a new era in 2015 when the pre-erythrocytic Plasmodium falciparum candidate RTS,S was favorably reviewed by the European Medicines Agency and subsequently introduced into national pilot implementation programs, marking the first human anti-parasite vaccine to pass regulatory scrutiny. Since the first trials published in 1997, RTS,S has been evaluated in a series of clinical trials culminating in Phase 3 testing, while testing of other pre-erythrocytic candidates (that target sporozoite- or liver-stage parasites), particularly whole sporozoite vaccines, has also increased. Interest in blood-stage candidates (that limit blood-stage parasite growth) subsided after disappointing human efficacy results, although new blood-stage targets and concepts may revive activity in this area. Over the past decade, testing of transmission-blocking vaccines (that kill mosquito/sexual-stage parasites) advanced to field trials and the first generation of placental malaria vaccines (that clear placenta-sequestering parasites) entered the clinic. Novel antigen discovery, human monoclonal antibodies, structural vaccinology, and improved platforms promise to expand on RTS,S and improve existing vaccine candidates.
Project description:BackgroundThe introduction of highly effective direct-acting antiviral (DAA) therapy for hepatitis C has led to calls to eliminate it as a public health threat through treatment-as-prevention. Recent studies suggest it is possible to develop a vaccine to prevent hepatitis C. Using a mathematical model, we examined the potential impact of a hepatitis C vaccine on the feasibility and cost of achieving the global WHO elimination target of an 80% reduction in incidence by 2030 in the era of DAA treatment.MethodsThe model was calibrated to 167 countries and included two population groups (people who inject drugs (PWID) and the general community), features of the care cascade, and the coverage of health systems to deliver services. Projections were made for 2018-2030.ResultsThe optimal incidence reduction strategy was to implement test and treat programmes among PWID, and in settings with high levels of community transmission undertake screening and treatment of the general population. With a vaccine available, the optimal strategy was to include vaccination within test and treat programmes, in addition to vaccinating adolescents in settings with high levels of community transmission. Of the 167 countries modelled, between 0 and 48 could achieve an 80% reduction in incidence without a vaccine. This increased to 15-113 countries if a 75% efficacious vaccine with a 10-year duration of protection were available. If a vaccination course cost US$200, vaccine use reduced the cost of elimination for 66 countries (40%) by an aggregate of US$7.4 (US$6.6-8.2) billion. For a US$50 per course vaccine, this increased to a US$9.8 (US$8.7-10.8) billion cost reduction across 78 countries (47%).ConclusionsThese findings strongly support the case for hepatitis C vaccine development as an urgent public health need, to ensure hepatitis C elimination is achievable and at substantially reduced costs for a majority of countries.
Project description:Hepatitis B is caused by the hepatitis B virus (HBV), which infects the liver and may lead to chronic liver disease, including cirrhosis and hepatocellular carcinoma. HBV represents a worldwide public health problem, causing major morbidity and mortality. Affordable, safe, and effective, hepatitis B vaccines are the best tools we have to control and prevent hepatitis B. In 2019, coverage of 3 doses of the hepatitis B vaccine reached 85% worldwide compared to around 30% in 2000. The effective implementation of hepatitis B vaccination programs has resulted in a substantial decrease in the HBV carrier rate and hepatitis B-related morbidity and mortality. This article summarizes the great triumphs of the hepatitis B vaccine, the first anticancer and virus-like-particle-based vaccine. In addition, existing unresolved issues and future perspectives on hepatitis B vaccination required for global prevention of HBV infection are discussed.
Project description:Low- and middle-income countries receive limited guidance from external entities about how to introduce vaccines. This is especially true for the Hepatitis E (HepE) vaccine, which is currently only commercially available in China. The aims of this qualitative study are to identify which attributes of the HepE disease and vaccine are considered important, and to compare desired promotion methods between different stakeholders. Stakeholders included experts (Centers for Disease Control and Prevention staff, health care providers, and researchers), and nonexperts included members of high-risk populations, HepE cases, and vaccinees. Participants' thoughts were coded and broadly summarized. We contacted 63 persons-35 experts and 28 nonexperts. Safety and effectiveness (but not price) of the vaccine, along with severity of disease and transmission route of infection, were all listed as important attributes. Emphasizing the importance of sharing stories from cases, relying on personal experiences, staying away from statistical explanations, and using the government as a source of promotion were other points repeatedly raised by the participants. Qualitative interviews with experts and nonexperts has revealed that focusing on attributes of disease severity and susceptibility to infection, as well as vaccine safety and effectiveness within stories of cases, are preferred ways to promote the vaccine.
Project description:The external institutional environment is the foundation for the survival and development of enterprises. Enterprises can only obtain legitimate and heterogeneous resources through continuous strategic reform and institutional innovation to match their internal strategies with the external environment. The paper selected the manufacturing enterprises that implemented service-oriented transformation strategies in China from 2016-2019 as a sample based on the realistic background of frequent institutional changes and overlapping market changes during China's economic transformation. The impact of different aspects of the institutional environment on service-oriented transformation and the moderating role of technological innovation capacity were examined empirically. The results showed that (1) improved government governance greatly facilitates the service-oriented transformation of manufacturing enterprises, which was more pronounced within the industry. The regulated development of the market facilitated service-oriented transformation within the industry in the short term, while the impact on cross-border transformation lagged. The improvement of the legalized business environment was conducive to the transformation of enterprises and promoted intra-industry transformation significantly more than cross-industry transformation. (2) Technological innovation capability strengthened the influence of institutional environment on intra-industry transformation, but had no significant impact on the relationship between institutional environment and cross-border transformation. (3) The moderating effect of technological innovation capability was markedly heterogeneous in terms of property rights and regional heterogeneity. The findings of this study provide an important reference for policy makers to break through the current institutional barriers to transformation and upgrading of the manufacturing industry, and to reshape and optimize the institutional environment for the integration and development of the secondary and tertiary industries.