Recent Occurrence, Diversity, and Candidate Vaccine Virus Selection for Pandemic H5N1: Alert Is in the Air.

The prevalence of the highly pathogenic avian influenza virus H5N1 in wild birds that migrate all over the world has resulted in the dissemination of this virus across Asia, Europe, Africa, North and South America, the Arctic continent, and Antarctica. So far, H5N1 clade 2.3.4.4.b has reached an almost global distribution, with the exception of Australia and New Zealand for autochthonous cases. H5N1 clade 2.3.4.4.b, derived from the broad-host-range A/Goose/Guangdong/1/96 (H5N1) lineage, has evolved, adapted, and spread to species other than birds, with potential mammal-to-mammal transmission. Many public health agencies consider H5N1 influenza a real pandemic threat. In this sense, we analyzed H5N1 hemagglutinin sequences from recent outbreaks in animals, clinical samples, antigenic prototypes of candidate vaccine viruses, and licensed human vaccines for H5N1 with the aim of shedding light on the development of an H5N1 vaccine suitable for a pandemic response, should one occur in the near future.

Ethical and Practical Considerations for an Agreement to Ensure Equitable Vaccine Access Comment on "More Pain, More Gain! The Delivery of COVID-19 Vaccines and the Pharmaceutical Industry's Role in Widening the Access Gap".

This paper discusses the potential of an international agreement to ensure equitable vaccine distribution, addressing the failures witnessed during the COVID-19 pandemic. COVAX was unable to prevent vaccine monopolization and unequal distribution, which led to significant disparities in vaccination rates and avoidable deaths. Any future agreement on equitable vaccine distribution must address ethical and practical issues to ensure global health equity and access. The proposed agreement should recognize healthcare as a human right and consider vaccines beyond mere commodities, emphasizing the social responsibility of pharmaceutical companies to prioritize affordability, availability, and accessibility, particularly for low-income countries (LICs). Voluntary licensing agreements are suggested as a means to enhance access to essential medicines. The paper also outlines the necessity of international cooperation, with robust compliance mechanisms, to effectively enforce such an agreement and mitigate future health crises.

Preparing for future pandemics while responding to the current ones in the midst of a planetary climate crisis: Can we face this triple global health challenge?

Global health faces the triple challenge of preparing for future pandemics while responding to current ones in the midst of a climate crisis. In this commentary, we discuss the heightened focus on pandemic preparedness after the COVID-19 pandemic and the risks that this may pose to addressing the elimination of AIDS, tuberculosis, hepatitis and malaria, established in the Sustainable Development Goals as target 3.3. Considering their interconnections with the climate crisis and advocating for global health justice, we identify impasses that such a dispute over priorities can imply, and comment on four fronts of actions that could contribute convergently to both agendas as well as to facing the consequences of climate change to health: strengthening health systems, global commitment to equitable access to strategic medicines, addressing social inequalities and joining efforts for health and climate justice We conclude that addressing these fronts safeguards the health rights of the most vulnerable to existing epidemics while enhancing readiness for future pandemics. Moreover, solutions must transcend technocratic approaches, necessitating the confrontation of inequalities perpetuated by systems of power and privilege fueling both health and climate crises. Ultimately, health justice should guide responses to this intricate triple global health challenge.

Balancing the benefits of vaccination: An envy-free strategy.

The Covid-19 pandemic revealed the difficulties of vaccinating a population under the circumstances marked by urgency and limited availability of doses while balancing benefits associated with distinct guidelines satisfying specific ethical criteria. We offer a vaccination strategy that may be useful in this regard. It relies on the mathematical concept of envy-freeness. We consider finding balance by allocating the resource among individuals that seem heterogeneous concerning the direct and indirect benefits of vaccination, depending on age. The proposed strategy adapts a constructive approach in the literature based on Sperner's Lemma to point out an approximate division of doses guaranteeing that both benefits are optimized each time a batch becomes available. Applications using data about population age distributions from diverse countries suggest that, among other features, this strategy maintains the desired balance, throughout the entire vaccination period. We discuss complementary aspects of the method in the context of epidemiological models of age-stratified Susceptible - Infected - Recovered (SIR) type.

Promoting healthy populations as a pandemic preparedness strategy: a simulation study from Mexico.

Background: The underlying health status of populations was a major determinant of the impact of the COVID-19 pandemic, particularly obesity prevalence. Mexico was one of the most severely affected countries during the COVID-19 pandemic and its obesity prevalence is among the highest in the world. It is unknown by how much the COVID-19 burden could have been reduced if systemic actions had been implemented to reduce excess weight in Mexico before the onset of the pandemic. Methods: Using a dynamic epidemic model based on nationwide data, we compare actual deaths with those under hypothetical scenarios assuming a lower body mass index in the Mexican population, as observed historically. We also model the number of deaths that would have been averted due to earlier implementation of front-of-pack warning labels or due to increases in taxes on sugar-sweetened beverages and non-essential high-energy foods in Mexico. Findings: We estimate that 52.5% (95% prediction interval (PI) 43.2, 61.6%) of COVID-19 deaths were attributable to obesity for adults aged 20-64 and 23.8% (95% PI 18.7, 29.1%) for those aged 65 and over. Had the population BMI distribution remained as it was in 2000, 2006, or 2012, COVID-19 deaths would have been reduced by an expected 20.6% (95% PI 16.9, 24.6%), 9.9% (95% PI 7.3, 12.9%), or 6.9% (95% PI 4.5, 9.5%), respectively. If the food-labelling intervention introduced in 2020 had been introduced in 2018, an expected 6.2% (95% PI 5.2, 7.3%) of COVID-19 deaths would have been averted. If taxes on sugar-sweetened beverages and high-energy foods had been doubled, trebled, or quadrupled in 2018, COVID-19 deaths would have been reduced by an expected 4.1% (95% PI 2.5, 5.7%), 7.9% (95% PI 4.9, 11.0%), or 11.6% (95% PI 7.3, 15.8%), respectively. Interpretation: Public health interventions targeting underlying population health, including non-communicable chronic diseases, is a promising line of action for pandemic preparedness that should be included in all pandemic plans. Funding: This study received funding from Bloomberg Philanthropies, awarded to Juan A. Rivera from the National Institute of Public Health; Community Jameel, the UK Medical Research Council (MRC), Kenneth C Griffin, and the World Health Organization.

Combining Digital and Molecular Approaches Using Health and Alternate Data Sources in a Next-Generation Surveillance System for Anticipating Outbreaks of Pandemic Potential.

Globally, millions of lives are impacted every year by infectious diseases outbreaks. Comprehensive and innovative surveillance strategies aiming at early alert and timely containment of emerging and reemerging pathogens are a pressing priority. Shortcomings and delays in current pathogen surveillance practices further disturbed informing responses, interventions, and mitigation of recent pandemics, including H1N1 influenza and SARS-CoV-2. We present the design principles of the architecture for an early-alert surveillance system that leverages the vast available data landscape, including syndromic data from primary health care, drug sales, and rumors from the lay media and social media to identify areas with an increased number of cases of respiratory disease. In these potentially affected areas, an intensive and fast sample collection and advanced high-throughput genome sequencing analyses would inform on circulating known or novel pathogens by metagenomics-enabled pathogen characterization. Concurrently, the integration of bioclimatic and socioeconomic data, as well as transportation and mobility network data, into a data analytics platform, coupled with advanced mathematical modeling using artificial intelligence or machine learning, will enable more accurate estimation of outbreak spread risk. Such an approach aims to readily identify and characterize regions in the early stages of an outbreak development, as well as model risk and patterns of spread, informing targeted mitigation and control measures. A fully operational system must integrate diverse and robust data streams to translate data into actionable intelligence and actions, ultimately paving the way toward constructing next-generation surveillance systems.

Recent occurrence, diversity, and candidate vaccine virus selection for pandemic H5N1: alert Is in the air

The prevalence of the highly pathogenic avian influenza virus H5N1 in wild birds that migrate all over the world has resulted in the dissemination of this virus across Asia, Europe, Africa, North and South America, the Arctic continent, and Antarctica. So far, H5N1 clade 2.3.4.4.b has reached an almost global distribution, with the exception of Australia and New Zealand for autochthonous cases. H5N1 clade 2.3.4.4.b, derived from the broad-host-range A/Goose/Guangdong/1/96 (H5N1) lineage, has evolved, adapted, and spread to species other than birds, with potential mammal-to-mammal transmission. Many public health agencies consider H5N1 influenza a real pandemic threat. In this sense, we analyzed H5N1 hemagglutinin sequences from recent outbreaks in animals, clinical samples, antigenic prototypes of candidate vaccine viruses, and licensed human vaccines for H5N1 with the aim of shedding light on the development of an H5N1 vaccine suitable for a pandemic response, should one occur in the near future.

The Experience of Testing for Coronavirus Disease (COVID-19) at a Single Diagnostic Center in Paraguay before the Introduction of Vaccination.

Soon after the declaration of the COVID-19 pandemic, the Institute for Health Sciences Research (IICS) of the National University of Asunción, Paraguay became a testing laboratory (COVID-Lab) for SARS-CoV-2. The COVID-Lab testing performance was assessed from 1 April 2020 to 12 May 2021. The effect of the pandemic on the IICS and how the COVID-Lab contributed to the academic and research activities of the institute were also assessed. IICS researchers and staff adjusted their work schedules to support the COVID-Lab. Of the 13,082 nasopharyngeal/oropharyngeal swabs processed, 2704 (20.7%) tested positive for SARS-CoV-2 by RT-PCR. Of the individuals testing positive, 55.4% were female and 48.3% were aged 21-40 years. Challenges faced by the COVID-Lab were unstable reagent access and insufficient staff; shifting obligations regarding research, academic instruction, and grantsmanship; and the continuous demands from the public for information on COVID-19. The IICS provided essential testing and reported on the progress of the pandemic. IICS researchers gained better laboratory equipment and expertise in molecular SARS-CoV-2 testing but struggled to manage their conflicting educational and additional research obligations during the pandemic, which affected their productivity. Therefore, policies protecting the time and resources of the faculty and staff engaged in pandemic-related work or research are necessary components of healthcare emergency preparedness.

Global SARS-CoV-2 genomic surveillance: What we have learned (so far).

The COVID-19 pandemic has brought significant challenges for genomic surveillance strategies in public health systems worldwide. During the past thirty-four months, many countries faced several epidemic waves of SARS-CoV-2 infections, driven mainly by the emergence and spread of novel variants. In that line, genomic surveillance has been a crucial toolkit to study the real-time SARS-CoV-2 evolution, for the assessment and optimization of novel diagnostic assays, and to improve the efficacy of existing vaccines. During the pandemic, the identification of emerging lineages carrying lineage-specific mutations (particularly those in the Receptor Binding domain) showed how these mutations might significantly impact viral transmissibility, protection from reinfection and vaccination. So far, an unprecedented number of SARS-CoV-2 viral genomes has been released in public databases (i.e., GISAID, and NCBI), achieving 14 million genome sequences available as of early-November 2022. In the present review, we summarise the global landscape of SARS-CoV-2 during the first thirty-four months of viral circulation and evolution. It demonstrates the urgency and importance of sustained investment in genomic surveillance strategies to timely identify the emergence of any potential viral pathogen or associated variants, which in turn is key to epidemic and pandemic preparedness.

Global SARS-CoV-2 genomic surveillance: what we have learned (so far)

The COVID-19 pandemic has brought significant challenges for genomic surveillance strategies in public health systems worldwide. During the past thirty-four months, many countries faced several epidemic waves of SARS-CoV-2 infections, driven mainly by the emergence and spread of novel variants. In that line, genomic surveillance has been a crucial toolkit to study the real-time SARS-CoV-2 evolution, for the assessment and optimization of novel diagnostic assays, and to improve the efficacy of existing vaccines. During the pandemic, the identification of emerging lineages carrying lineage-specific mutations (particularly those in the Receptor Binding domain) showed how these mutations might significantly impact viral transmissibility, protection from reinfection and vaccination. So far, an unprecedented number of SARS-CoV-2 viral genomes has been released in public databases (i.e., GISAID, and NCBI), achieving 14 million genome sequences available as of early-November 2022. In the present review, we summarise the global landscape of SARS-CoV-2 during the first thirty-four months of viral circulation and evolution. It demonstrates the urgency and importance of sustained investment in genomic surveillance strategies to timely identify the emergence of any potential viral pathogen or associated variants, which in turn is key to epidemic and pandemic preparedness.

COVID-19 and Future Disease X in Circular Economy Transition: Redesigning Pandemic Preparedness to Prevent a Global Disaster.

The COVID-19 pandemic exposed a world surprisingly unprepared to respond to the new epidemiological scenario, even the developed countries, in spite of warnings from scientists since the 1990s. These alerts warned on the risks of an exponential increase in emergence of potentially pandemic zoonotic infectious diseases related to disruptive ecological niches in different regions of the globe, such as H1N1 Influenza, SARS, MERS, Zika, avian flu, swine flu, and Ebola, and also on the risks of a future and more lethal Disease X. We examine this global public health failure in anticipating and responding to the pandemic, stressing the urgent need for an innovative global pandemic preparedness system in the current transition from linear economy to a circular economy. Evidence provided here indicates that this novel preventive-based and resource-saving preparedness system could contribute to reverse the detrimental impacts of the pandemic on global economy and increase its resilience. Individual protection, contact tracing, and lockdown have proved to be just partially effective to respond to the spillover of viral zoonosis into the human population, and for most of these pathogens, vaccines are not yet available. As for COVID-19 vaccines, in spite of the extraordinary investments and unprecedented advances in innovative vaccines in few months, most of these products are expected to be available to more vulnerable developing countries' populations only by mid-2022. Furthermore, even when these vaccines are available, constraints such as low efficacy, waning immunity, new concerning COVID-19 variants, adverse events, and vaccine hesitancy might possibly restrict their public health impact and could contribute to aggravate the pandemic scenario. Considering these constraints and the severe global economic and social crises resulting from the lack of adequate preparedness and delayed effective response to COVID-19 and possibly to a future Disease X, we propose a pro-active global eco-social pandemic preparedness system. This novel system, based on One Health paradigm and on artificial intelligence and machine learning, is expected to incorporate "spillover" foresight and management into global preparedness and timely response. Designed to mitigate damage from outbreaks and minimize human morbidity and mortality, this approach to pandemic foresight and preparedness will be key to prevent a global disaster.

Vaccine Innovation for Pandemic Preparedness: Patent Landscape, Global Sustainability, and Circular Bioeconomy in Post-COVID-19 era.

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.

The politics of COVID-19 vaccination in middle-income countries: Lessons from Brazil.

As the world struggles to meet the challenges of vaccination against COVID-19, more attention needs to be paid to issues faced by countries at different income levels. Middle-income countries (MICs) typically lack the resources and regulatory capacities to pursue strategies that wealthier countries do, but they also face different sets of challenges and opportunities than low-income countries (LICs). We focus on three dimensions of vaccination: procurement and production; regulation of marketing registration; and distribution and uptake. For each dimension we show the distinct challenges and opportunities faced by MICs. We illustrate these challenges and opportunities with the case of Brazil, showing how each dimension has been affected by intense political conflicts. Brazil's procurement and production strategy, which builds on a long trajectory of local production and technology transfer, has been riddled by conflicts between the national government and state governments. The regulatory approval process, based around one of Latin America's most highly-regarded regulatory authorities, has also been subject to acute inter- and intra-governmental conflicts. And with regard to distribution and uptake, in the face of high uncertainty, even with a solid health infrastructure, Brazil encounters difficulties in promoting vaccine delivery. The research also reveals the importance of coordination among these dimensions, in Brazil and beyond. Pandemic preparedness and response must include sharing knowledge of how to produce vaccines and recognition of the crucial linkages between procurement, regulation, delivery, and uptake that are necessary for ensuring access to these products.

H7N9 pandemic preparedness: A large-scale production of a split inactivated vaccine.

In March 2013 it was reported by the World Health Organization (WHO) the first cases of human infections with avian influenza virus A (H7N9). From 2013 to December 2019, 1568 cases have been reported with 616 deaths. H7N9 infection has been associated with high morbidity and mortality rates, and vaccination is currently the most effective way to prevent infections and consequently flu-related severe illness. Developing and producing vaccines against pandemic influenza viruses is the main strategy for a response to a possible pandemic. This study aims to present the production of three industrial lots under current Good Manufacturing Practices (cGMP) of the active antigen used to produce the pandemic influenza vaccine candidate against A(H7N9). These batches were characterized and evaluated for quality standards and tested for immunogenicity in mice. The average yield was 173.50 ± 7.88 µg/mL of hemagglutinin and all the preparations met all the required specifications. The formulated H7N9 vaccine is poorly immunogenic and needs to be adjuvanted with an oil in water emulsion adjuvant (IB160) to achieve a best immune response, in a prime and in a boost scheme. These data are important for initial production planning and preparedness in the case of a H7N9 pandemic.

H7N9 pandemic preparedness: a large-scale production of a split inactivated vaccine

In March 2013 it was reported by the World Health Organization (WHO) the first cases of human infections with avian influenza virus A (H7N9). From 2013 to December 2019, 1568 cases have been reported with 616 deaths. H7N9 infection has been associated with high morbidity and mortality rates, and vaccination is currently the most effective way to prevent infections and consequently flu-related severe illness. Developing and producing vaccines against pandemic influenza viruses is the main strategy for a response to a possible pandemic. This study aims to present the production of three industrial lots under current Good Manufacturing Practices (cGMP) of the active antigen used to produce the pandemic influenza vaccine candidate against A(H7N9). These batches were characterized and evaluated for quality standards and tested for immunogenicity in mice. The average yield was 173.50 ± 7.88 μg/mL of hemagglutinin and all the preparations met all the required specifications. The formulated H7N9 vaccine is poorly immunogenic and needs to be adjuvanted with an oil in water emulsion adjuvant (IB160) to achieve a best immune response, in a prime and in a boost scheme. These data are important for initial production planning and preparedness in the case of a H7N9 pandemic.