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From the One Health (OH) perspective, the achievement of better public health results depends on effective strategies and interventions based on integrated research in diverse sectors of activity (human health, animal health, agriculture, and environment). The central topic in the United Nations 2030 Agenda aims at a world free of hunger, poverty, and severe disease through the achievement of 17 Sustainable Development Goals (SDGs). The objective of the present study is to evaluate countries and applicants of technologies patented between 2015-2020. From this methodological perspective, searches have been carried out in this study on the global patent database documents available, using specific search strategies for technologies related to challenging diseases for achieving SDGs, such as neglected communicable and non-communicable diseases: diarrhea, tuberculosis, malaria, obesity, cardiovascular diseases, diabetes, lung cancer, human schistosomiasis, and Zika.

In this article, we present breakthroughs and challenges in vaccine development for COVID-19 pandemic, discussing issues related to pandemic preparedness and their implications for circular bioeconomy and sustainability. Notwithstanding the unprecedented accelerated speed of COVID-19 vaccine development, just 9 months after the emergence of the pandemic in Wuhan, China, benefiting from previous developments in SARS and MERS vaccines, significant gaps persist in global vaccine preparedness. These gaps include issues related to immunity and protection, particularly to the limited vaccine protection against recent emergence of concerning new viral variants in the UK, South Africa, and Brazil and the consequent need for vaccine redesign. We examine these gaps and discuss the main issues that could impact on global vaccine availability in the current pandemic scenario: (1) breakthroughs and constraints in development and production of leading global COVID-19 vaccines; (2) innovation and technological development advances and gaps, providing information on global patent assignees for COVID-19, SARS, and MERS vaccine patents; (3) local capacity for development and production of COVID-19, SARS, and MERS vaccines in three emerging agro-based countries (India, Brazil, and South Africa); and (4) future scenarios, examining how these issues and vaccines redesign for new SARS-CoV-2 variants could impact on global access to vaccines and implications for circular bioeconomy and sustainability in the post-COVID era.

This chapter provides an analysis of global trends in genomic vaccines, a radical innovation breakthrough (RIB), from technological foresight and pandemic preparedness perspectives, crucial in times of COVID-19. From this conceptual framework, the state-of-the-art and technological prospects for these genomic vaccines are examined, based on a search on scientific publications and on patents for the period 2010–2020, presenting the vaccine patent landscape for the period. This search provides an overview of recent breakthroughs in genomic vaccines and two other related RIBs, gene editing and gene therapy, and identifies novel strategies that could positively contribute to the development of future genomic vaccines to pandemic diseases and COVID-19. Our results evidence in the last decade extraordinary advances in genetic approaches, gene editing and gene therapy, and the rapid development of innovative DNA/RNA vaccines for the prevention and immunotherapy of an extensive diversity of diseases, from the neglected infectious ones to cancer therapy. These results highlight the flexibility of vaccine technological platforms, crucial for response to pandemics and COVID-19, including hepatitis B, varicella, chronic obstructive pulmonary disease, autoimmune diseases – systemic lupus erythematosus, lupus nephritis, and autoimmune myasthenia gravis – and finally a new nucleic acid sequence for immunogenicity to SARS-CoV-2.

Innovative preventive vaccines against emerging and neglected infectious diseases, such as Zika, dengue, influenza, and HIV/AIDS, are examined from a global sustainability perspective in this chapter, aiming to integrate public health and innovation governance approaches. Innovation-intensive vaccines with reduced adverse effects can have an enormous impact on life expectancy and on the quality of life of the global population, but in contrast only one of the SDGs, SDG3, refers directly to vaccines (3.b.1). However, this chapter also identifies seven other SDGs strongly related to vaccines and six additional SDGs related to vaccines, leading to a total of 14 vaccine-related goals in 17 SDGs. Two of these goals are related to innovation and technological development of vaccines (SDG9 and SDG17). The authors examine vaccine performance indicators and current technological and regulatory obstacles to achieve these goals, particularly affecting developing countries, and propose STI governance strategies to overcome these gaps and increase access to vaccines. Policy recommendations for vaccine funding and incentives for innovation, development, and vaccine production are made. Recommendations are also given for specific vaccine STI performance indicators and strategies to achieve the 14 vaccine-related SDGs.

This chapter provides an overview, from bioeconomic and global sustainability perspectives, of the main constraints to the current global vaccine innovation system for achieving Sustainable Development Goals – SDGs. Biotechnology market trends, gaps in vaccine coverage against emerging and neglected diseases, and patent protection and regulation are discussed. A structured long-term “public-return-driven” innovation model to overcome vaccine market failure is proposed.

Emerging and resurgent arboviral diseases are a major public health problem for developing countries, particularly in Latin America and Africa, for the severity of their symptoms and lethality. Vaccines are recognized as the most powerful preventive, low-risk and cost-effective interventions. For this reason, vaccines against these arboviral diseases could have an extensive impact on global health. Nevertheless, many gaps persist in innovation and technological development of these vaccines and it is necessary and urgent to accelerate new funding mechanisms and incentives, such as “patent pools”, with active participation of manufacturers in developing countries, to assure their cost-effectiveness, efficacy and minimize their potential adverse effects. In this global scenario, intellectual property, especially patents documents, have emerged as a crucial issue for vaccine development. The global patent landscape for vaccines against these four arboviral diseases has undergone drastic changes in the past 5 years, with breakthroughs resulting from advances in molecular biology and genetic engineering: DNA vaccines, recombinant vaccines based on antigens expressed in vectors (viral, bacterial, yeast) and vaccines obtained through reverse vaccinology, with the selection of potential candidates at the genetic level rather than the protein level. Our main aim is to transcend the conventional debate on vaccine development and ethical, regulatory and policy issues, already explored in many scientific publications in the past three decades and determine which of these issues should be considered new and specific to this new perspective. Finally, an adequate use of patent documents, as indicated here, can be a valuable source of information, supporting technological prospect tools in more effective knowledge governance strategies.

We discuss the complex eco-social factors involved in the puzzle of the unexpected rapid viral spread in the ongoing Brazilian yellow fever (YF) outbreak, which has increased the reurbanisation risk of a disease without urban cases in Brazil since 1942. Indeed, this rapid spatial viral dissemination to the Southeast and South regions, now circulating in the Atlantic Forest fragments close to peri-urban areas of the main Brazilian megalopolises (Sao Paulo and Rio de Janeiro) has led to an exponential increase in the number of yellow fever cases. In less than 18 months, 1,833 confirmed cases and 578 deaths were recorded most of them reported in the Southeast region (99,9%). Large epizooties in monkeys and other non-human primates (NHPs) were communicated in the country with 732 YF virus (YFV) laboratory confirmed events only in the 2017/2018 monitoring period. We also discuss the peculiarities and similarities of the current outbreak when compared with previous great epidemics, examining several hypotheses to explain the recent unexpected acceleration of epizootic waves in the sylvatic cycle of the YFV together with the role of human, NHPs and mosquito mobility with respect to viral spread. We conclude that the most feasible hypothesis to explain this rapidity would be related to human behavior combined with ecological changes that promoted a significant increase in mosquito and NHP densities and their contacts with humans. We emphasize the urgent need for an adequate response to this outbreak such as extending immunisation coverage to the whole Brazilian population and developing novel strategies for immunisation of NHPs confined in selected reserve areas and zoos. Finally, we stress the urgent need to improve the quality of response in order to prevent future outbreaks and a catastrophic reurbanisation of the disease in Brazil and other South American countries. Continuous monitoring of YFV receptivity and vulnerability conditions with effective control of the urban vector Aedes aegypti and significant investments in YF vaccine production capacity and research and development for reduction of adverse effects are of the highest priority.

RESUMO Estudos sobre o ensino da patologia no Brasil são escassos e mostram um cenário desmotivador para estudantes e professores. Embora essa disciplina seja fundamental à formação médica, o distanciamento entre o seu ensino e o das demais disciplinas clínicas leva ao não reconhecimento, por parte dos estudantes, da importância da patologia para a formação profissional, especialmente na área de doenças infecciosas. O objetivo deste estudo foi investigar o processo de formação e produção do conhecimento em patologia em três faculdades de Medicina com ensino tradicional no Estado do Rio de Janeiro e seu impacto na atuação de patologistas e infectologistas. Trata-se de um estudo qualitativo com utilização da técnica do discurso do sujeito coletivo em entrevistas semiestruturadas. Foram entrevistados sete professores de patologia de duas faculdades públicas e de uma particular e dez médicos - cinco patologistas que atuavam no Rio de Janeiro e cinco infectologistas de um centro de referências em doenças infecciosas no Rio de Janeiro. A disciplina de patologia é oferecida de forma descontextualizada em períodos específicos. Professores reconhecem que aulas descontextualizadas não estimulam o interesse pela especialidade nem preparam estudantes para interação com patologistas e serviços de anatomia patológica. Para infectologistas, falta percepção da importância da patologia na graduação, o que para patologistas gera dificuldades na interação com infectologistas, resultando em preenchimento incompleto de solicitação de exames histopatológicos, dificuldade na interpretação de laudos e envio inadequado de amostras. Infectologistas e patologistas acreditam que mais aulas práticas, maior integração com a clínica e a presença do patologista em outros cenários de aprendizagem aumentem o interesse pela patologia. Todos os professores, infectologistas e patologistas pesquisados reconheceram a existência de lacunas no ensino-aprendizagem na disciplina de patologia na graduação médica e a necessidade de reformulação para torná-la uma especialidade mais interessante e alinhada à realidade profissional. ABSTRACT Studies on the teaching of pathology are scarce in Brazil and show a demotivating scenario for students and professors. Although it is fundamental for medical training, the distance between pathology and other clinical disciplines leads to students not recognizing the importance of pathology for their professional education, especially in the field of infectious diseases. The aim of this study was to investigate the teaching-learning process of pathology in three medical schools in the state of Rio de Janeiro which offer traditional teaching, and its impact on the work of pathologists and infectious disease specialists. It is a qualitative study using the collective subject discourse technique in semi-structured interviews. We interviewed seven pathology professors from the three medical schools along with 10 physicians, five pathologists working in pathology laboratories and five infectious disease specialists from a referral center on infectious diseases in Rio de Janeiro. The discipline of pathology is taught in a non-contextualized manner limited to a few semesters. Professors recognize that non-contextualized classes neither stimulate interest in the specialty nor prepare students for interaction with pathologists and pathology laboratories. For infectious disease specialists, medical undergraduates’ lack of perception regarding the importance of pathology leads to difficult interaction between pathologists and infectious disease specialists. This difficult interaction translates into incomplete histopathological requests, difficulty in interpreting pathology reports and inadequate sending of samples. Infectious disease specialists and pathologists believe that a focus on more practical activities, greater integration with clinical disciplines and the presence of pathologists in other learning scenarios would increase interest in pathology. All the professors and physicians surveyed acknowledged the existence of gaps in the teaching of pathology in medical schools and the need for a reformulation to make it a more interesting discipline and aligned with future practice.

The research agenda towards an HIV cure is building rapidly. In this article, we discuss the reasons for and methodological approach to using mathematical modelling and cost-effectiveness analysis in this agenda. We provide a brief description of the proof of concept for cure and the current directions of cure research. We then review the types of clinical economic evaluations, including cost analysis, cost-benefit analysis and cost-effectiveness analysis. We describe the use of mathematical modelling and cost-effectiveness analysis early in the HIV epidemic as well as in the era of combination antiretroviral therapy. We then highlight the novel methodology of Value of Information (VOI) analysis and its potential role in the planning of clinical trials. We close with recommendations for modelling and cost-effectiveness analysis in the HIV cure agenda.

Partnerships, technology transfer and targeted policies are needed to accelerate Brazil's participation in global vaccine research and development.

This article discusses the peculiar conditions that favoured the unexpected introduction of Zika virus into the poorest northeastern region of Brazil in 2015, its speed of transmission to other Brazilian states, other Latin American countries and other regions, and the severity of related neurological disorders in newborns and adults. Contrasting with evidence that Zika had so far caused only mild cases in humans in the last six decades, the epidemiological scenario of this outbreak in Brazil indicates dramatic health effects: in 2015, an increase of 20-fold in notified cases of microcephaly and/or central nervous system (CNS) alterations suggestive of Zika congenital infection, followed by an exponential increase in 2016, with 2366 cumulative cases confirmed in the country by the end of December 2016. A significant increase in Guillain-Barré syndrome in adults has also been reported. Factors involved in viral dissemination, neural pathogenesis and routes of transmission in Brazil are examined, such as the role of social and environmental factors and the controversies involved in the hypothesis of antibody-dependent enhancement, to explain the incidence of congenital Zika syndrome in Brazil. Responses to the Zika outbreak and the development of new products are also discussed.

The quest for a cure for HIV remains a timely and key challenge for the HIV research community. Despite significant scientific advances, current HIV therapy regimens do not completely eliminate the negative impact of HIV on the immune system; and the economic impact of treating all people infected with HIV globally, for the duration of their lifetimes, presents significant challenges. This article discusses, from a multi-disciplinary approach, critical social, behavioral, ethical, and economic issues permeating the HIV cure research agenda. As part of a search for an HIV cure, both the perspective of patients/participants and clinical researchers should be taken into account. In addition, continued efforts should be made to involve and educate the broader community.

Desde o início da pandemia de HIV/aids, a imunoterapia vem sendo utilizada como alternativa terapêutica numa tentativa de estimular uma resposta do sistema imunológico contra o agente agressor. Esta abordagem tem sido considerada promissora para obtenção do controle da infecção em longo prazo. A administração de células apresentadoras de antígeno, em especial células dendríticas, é fundamentada pelos conceitos de imunoterapia passiva e de terapia celular ativa (vacina terapêutica) além da perspectiva da eliminação dos chamados reservatórios virais, unindo assim estas diversas estratégias de intervenção. Dentre os diferentes antígenos do HIV utilizados para pulsar as células dendríticas, alguns dos melhores resultados foram obtidos com a inativação química do vírus, preservando a integridade da estrutura da sua superfície.Há alguns anos nosso grupo vem trabalhando com terapia celular baseada em células dendríticas derivadas de monócitos autólogos, pulsadas com HIV inativado quimicamente, seguindo o protocolo descrito por Lu e colaboradores em 2004. Aqui, nós apresentamos os resultados de um ensaio clínico de fase I/II que teve como objetivos avaliar a tolerância, segurança e impacto imunovirológico, de diferentes formulações do produto em pacientes cronicamente infectados pelo HIV, sem uso de antirretrovirais. Os participantes foram alocados em três braços para receber composições distintas: 3x107 células dendríticas sem pulso adicional de HIV inativado (Braço A), 3x106 células dendríticas com pulso adicional de HIV inativado (Braço B) ou 3x107 células dendríticas com pulso adicional de HIV inativado (Braço C). O número de participantes no braço A evoluiu com uma considerável diminuição ao longo do período de observação do estudo, prejudicando as avaliações. As análises dos outros braços mostraram que as preparações foram seguras, não se observando eventos adversos relacionados à intervenção. Os resultados sugeriram um aumento na carga viral plasmática associados a uma redução das sub-populações de linfócitos TCD4+ e TCD8+ nos pacientes do braço C além de uma redução na quantidade de linfócitos T reguladores nos indivíduos do braço B Since the beginning of the HIV / aids pandemic, immunotherapy is being used as an alternative therapy in attempt to stimulate an immune response against the pathogenic agent. This approach has been considered as promising for achieving the control of infection in the long term. Administration of antigen presenting cells, particularly dendritic cells is based on the concepts of passive immunotherapy and active cellular therapy (therapeutic vaccine), with the perspective of eliminating the so-called viral reservoirs, thus joining different intervention strategies. From different antigens tested for loading DCs, some of the best results were obtained with chemically inactivated virus, which preserves its surface proteins.Our group has been working with cellular therapy based on dendritic cells derived from autologous monocytes pulsed with chemicallyinactivatedHIV, following the protocol described by Lu et al in 2004.Here, we present the results of a phase I / II clinical trial aimed to evaluate tolerance, safety and immunovirological impact of different product formulations in chronically HIV-infected individuals, naïve for antiretroviral treatment.Participants were allocated to receive: 3x107 un-pulsed DCs (Arm A), 3x106 HIV-pulsed DCs (Arm B) or 3x107 HIV-pulsed DCs (Arm C). The number of participants in the arm A evolved with a considerable decrease over the study, so any considerations about effect of DCs without antigen overload were difficult to carry out. Outcomes in other arms showedthat they were safe, with no adverse events related to the products. The results suggested an increase in plasma viral load and decline in CD4+ and CD8+ T cells subpopulations after intervention in arm C. Additionally, we observed a decrease in percentage of regulatory T cells in arm B patients