COVID-19 vaccine research and development: ethical issues.

The achievements of vaccine research and development bring a hope to our societies that we may cope with the COVID-19 pandemic. There are two aspects that should be maintained in balance: the immediate necessity for speed of vaccine research and the inherent need for protection of research subjects, which is the foremost concern of research ethics. This narrative review highlights ethical issues in COVID-19 vaccine research and development that every stakeholder needs to be aware of and to consider.

Hamster, a close model for visceral leishmaniasis: Opportunities and challenges.

AIM: Visceral leishmaniasis (VL) caused by parasites belonging to genus Leishmania (L.) is classified as a category I disease by the TDR/WHO. The understanding of the pathogenesis of this disease was built from the findings of available experimental models. Among all available models, the Syrian hamster (Mesocricetus auratus) is the most suitable model for the experimental representation of VL. In this review, we have focused on the opportunities and challenges of using the hamster as an experimental model for visceral leishmaniasis. METHODS: The studies referenced in this review were based on searches in PubMed and Google Scholar without a specific timeline. We collected study results underlining the clinicopathological response, immunopathogenesis and factors determining the outcome of VL in hamsters. Particular emphasis was given in the context of developing new therapeutics and testing potential candidates for vaccine development. CONCLUSION: Among all animal models, M. auratus is undoubtedly a better animal model for immunopathogenesis, drug discovery and vaccine development studies of VL infection. But, further optimization of this animal model is required to mimic human VL completely.

Computational modelling approaches to vaccinology.

Excepting the Peripheral and Central Nervous Systems, the Immune System is the most complex of somatic systems in higher animals. This complexity manifests itself at many levels from the molecular to that of the whole organism. Much insight into this confounding complexity can be gained through computational simulation. Such simulations range in application from epitope prediction through to the modelling of vaccination strategies. In this review, we evaluate selectively various key applications relevant to computational vaccinology: these include technique that operates at different scale that is, from molecular to organisms and even to population level.

Funding HIV-vaccine research in developing countries-what is wrong with IAVI's recommendation?

The International AIDS Vaccine Initiative recommends targeting resources to research institutions in developing countries in order to accelerate the development of an effective HIV vaccine. In contrast, this paper shows that neither lump-sum nor in-kind transfers are an effective policy. We analyze several financing mechanisms as a means to overcome the lack of depth in HIV-vaccine research in a non-cooperative framework. At first, we point to cases in which financial support is actually counterproductive. Then we analyze whether in-kind transfers are preferable to lump-sum transfers. Even if donors prefer aid in kind because the incentives for moral hazard of recipients can be reduced, we demonstrate that it is effective only if recipients have cost advantages.

Comprehensive analytics of COVID-19 vaccine research: From topic modeling to topic classification.

COVID-19 vaccine research has played a vital role in successfully controlling the pandemic, and the research surrounding the coronavirus vaccine is ever-evolving and accruing. These enormous efforts in knowledge production necessitate a structured analysis as secondary research to extract useful insights. In this study, comprehensive analytics was performed to extract these insights, which has moved the boundaries of data analytics in secondary research in the vaccine field by utilizing topic modeling, sentiment analysis, and topic classification based on the abstracts of related publications indexed in Scopus and PubMed. By applying topic modeling to 4803 abstracts filtered by this study criterion, 8 research arenas were identified by merging related topics. The extracted research areas were entitled "Reporting," "Acceptance," "Reaction," "Surveyed Opinions," "Pregnancy," "Titer of Variants," "Categorized Surveys," and "International Approaches." Moreover, the investigation of topics sentiments variations over time led to identifying researchers' attitudes and focus in various years from 2020 to 2022. Finally, a CNN-LSTM classification model was developed to predict the dominant topics and sentiments of new documents based on the 25 pre-determined topics with 75 % accuracy. The findings of this study can be utilized for future research design in this area by quickly grasping the structure of the current research on the COVID-19 vaccine. Through the findings of current research, a classification model was developed to classify the topic of a new article as one of the identified topics. Also, vaccine manufacturing firms will achieve a niche market by having a schema to invest in the gap of fields that have yet to be concentrated in extracted topics.

Prospects and Challenges in Developing mRNA Vaccines for Infectious Diseases and Oncogenic Viruses.

mRNA vaccines have emerged as an optimistic technological platform for vaccine innovation in this new scientific era. mRNA vaccines have dramatically altered the domain of vaccinology by offering a versatile and rapid approach to combating infectious diseases and virus-induced cancers. Clinical trials have demonstrated efficacy rates of 94-95% in preventing COVID-19, and mRNA vaccines have been increasingly recognized as a powerful vaccine platform. Although mRNA vaccines have played an essential role in the COVID-19 pandemic, they still have several limitations; their instability and degradation affect their storage, delivery, and over-all efficiency. mRNA is typically enclosed in a transport mechanism to facilitate its entry into the target cell because it is an unstable and negatively charged molecule. For instance, mRNA that is given using lipid-nanoparticle-based vaccine delivery systems (LNPs) solely enters cells through endocytosis, establishing an endosome without damaging the cell membrane. The COVID-19 pandemic has accelerated the development of mRNA vaccine platforms used to treat and prevent several infectious diseases. This technology has the potential to change the future course of the disease by providing a safe and effective way to combat infectious diseases and cancer. A single-stranded genetic sequence found in mRNA vaccines instructs host cells to produce proteins inside ribosomes to elicit immunological responses and prepare the immune system to fight infections or cancer cells. The potential applications of mRNA vaccine technology are vast and can lead to the development of a preferred vaccine pattern. As a result, a new generation of vaccinations has gradually gained popularity and access to the general population. To adapt the design of an antigen, and even combine sequences from different variations in response to new changes in the viral genome, mRNA vaccines may be used. Current mRNA vaccines provide adequate safety and protection, but the duration of that protection can only be determined if further clinical research is conducted.

MHC tetramer technology: Exploring T cell biology in health and disease.

Major histocompatibility complex (MHC) tetramers stand as formidable tools within T cell biology, facilitating the exploration and comprehension of immune responses. These artificial molecules, comprising four bound MHC molecules, typically with a specified peptide and a fluorescent label, play a pivotal role in characterizing T cell subsets, monitoring clonal expansion, and unraveling T cell dynamics during responses to infections or immunotherapies. Beyond their applications in T cell biology, MHC tetramers prove valuable in investigating a spectrum of diseases such as infectious diseases, autoimmune disorders, and cancers. Their instrumental role extends to vaccine research and development. Notably, when appropriately configured, tetramers transcend T cell biology research and find utility in exploring natural killer T cells and contributing to specific T cell clonal deletions.

Improving Middle-Income Countries Access to Vaccines. A Blueprint to Overcome Current Challenges.

The Global Health Consortium at Florida International University developed an end-to-end solution framework based on the input of a diverse panel of experts from middle-income country (MIC) government agencies, public health think tanks, academia, and nonprofit organizations to identify mechanisms to help MIC governments and stakeholders increase access to novel vaccines for infectious diseases. The resultant layout can be deployed to improve vaccine discovery and development, strengthen regulatory processes, and boost vaccine production, access, and implementation. Mechanisms include policies and incentives MIC governments can use to stimulate vaccine investment and activity, as well as actions government agencies can take together with other stakeholders to coordinate efforts or build capabilities. Through a series of individual virtual interviews, we engaged diverse experts from MIC government agencies, public health think tanks, academia, and nonprofit organizations who understand the vaccine ecosystem, immunization policies, and population health financing at global, regional, and country levels. Responses were mapped, and in-depth questions were prepared for a group virtual discussion. This paper is the result of such a group discussion. The panel identified clear opportunities for MICs to improve locally-driven innovations and future access to novel vaccines. It proposes a solution framework for countries considering investing in vaccine research and development and innovation to use as a guide to evaluate the steps they could take to improve such an environment and incentivize innovation in vaccine development. It is hoped that this end-to-end solution framework will become a key resource to help MICs strengthen policies and take more actions to make such improvements.

Rehoming and Other Refinements and Replacement in Procedures Using Golden Hamsters in SARS-CoV-2 Vaccine Research.

Effective vaccines are needed to fight the COVID-19 pandemic. Forty golden hamsters were inoculated with two promising vaccine candidates and eighteen animals were used in pilot trials with viral challenge. ELISA assays were performed to determine endpoint serum titres for specific antibodies and virus neutralisation tests were used to evaluate the efficacy of antibodies. All tests with serum from vaccinated hamsters were negative even after booster vaccinations and changes in vaccination protocol. We concluded that antibodies did not have sufficient neutralising properties. Refinements were observed at all steps, and the in vitro method (virus neutralisation test) presented a replacement measure and ultimately lead to a reduction in the total number of animals used in the project. The institutional animal welfare officer and institutional designated veterinarian approved the reuse or rehoming of the surplus animals. Simple socialization procedures were performed and ultimately 19 animals were rehomed, and feedback was collected. Recently, FELASA published recommendations for rehoming of animals used for scientific and educational purposes, with species-specific guidelines, including mice, rats, and rabbits. Based on our positive experience and feedback from adopters, we concluded that the rehoming of rodents, including hamsters, is not only possible, but highly recommended.

Manipulation of host immune defenses by effector proteins delivered from multiple secretion systems of Salmonella and its application in vaccine research.

Salmonella is an important zoonotic bacterial species and hazardous for the health of human beings and livestock globally. Depending on the host, Salmonella can cause diseases ranging from gastroenteritis to life-threatening systemic infection. In this review, we discuss the effector proteins used by Salmonella to evade or manipulate four different levels of host immune defenses: commensal flora, intestinal epithelial-mucosal barrier, innate and adaptive immunity. At present, Salmonella has evolved a variety of strategies against host defense mechanisms, among which various effector proteins delivered by the secretory systems play a key role. During its passage through the digestive system, Salmonella has to face the intact intestinal epithelial barrier as well as competition with commensal flora. After invasion of host cells, Salmonella manipulates inflammatory pathways, ubiquitination and autophagy processes with the help of effector proteins. Finally, Salmonella evades the adaptive immune system by interfering the migration of dendritic cells and interacting with T and B lymphocytes. In conclusion, Salmonella can manipulate multiple aspects of host defense to promote its replication in the host.

A research and development (R&D) roadmap for broadly protective coronavirus vaccines: A pandemic preparedness strategy.

Broadly protective coronavirus vaccines are an important tool for protecting against future SARS-CoV-2 variants and could play a critical role in mitigating the impact of future outbreaks or pandemics caused by novel coronaviruses. The Coronavirus Vaccines Research and Development (R&D) Roadmap (CVR) is aimed at promoting the development of such vaccines. The CVR, funded by the Bill & Melinda Gates Foundation and The Rockefeller Foundation, was generated through a collaborative and iterative process, which was led by the Center for Infectious Disease Research and Policy (CIDRAP) at the University of Minnesota and involved 50 international subject matter experts and recognized leaders in the field. This report summarizes the major issues and areas of research outlined in the CVR and identifies high-priority milestones. The CVR covers a 6-year timeframe and is organized into five topic areas: virology, immunology, vaccinology, animal and human infection models, and policy and finance. Included in each topic area are key barriers, gaps, strategic goals, milestones, and additional R&D priorities. The roadmap includes 20 goals and 86 R&D milestones, 26 of which are ranked as high priority. By identifying key issues, and milestones for addressing them, the CVR provides a framework to guide funding and research campaigns that promote the development of broadly protective coronavirus vaccines.

Willingness to Accept Expedited COVID-19 Vaccine Research for Children Aged <12 Years After Adult Vaccine Approval.

PURPOSE: The goal of this study was to assess if caregivers' attitudes toward the regulatory process of approving the vaccine against coronavirus disease 2019 (COVID-19) for children aged <12 years changed after a vaccine was approved for adults. METHODS: This was a larger scale COVIPAS (COVID-19 Parental Attitude Study) survey of caregivers presenting with their children aged ≤12 years for emergency care in 12 hospitals in the United States, Canada, and Israel. The study compared willingness to support abridged research into COVID-19 vaccines for children between the peak of the pandemic (March-May 2020) and after a COVID-19 vaccine became available for adults (December 2020-March 2021). FINDINGS: A total of 1956 surveys were included in the analyses. Overall, 385 (30.9%) caregivers in the pre-vaccine approval period and 250 (35.3%) caregivers in the post-adult vaccine phase supported abridged research into COVID-19 vaccines (P < 0.001). In both phases, mothers were less likely to favor abridged approval. Those with children who were fully vaccinated based on the pediatric schedule in their country favored abridged approval in phase 1 (odds ratio, 1.98; 95% confidence interval, 1.31-3.08) but less so in phase 2. In both phases, age and concerns of parents that they had COVID-19 or their child had COVID-19 were not associated with changes in response between phases. IMPLICATIONS: Willingness to expedite vaccine approval increased after the emergency approval of COVID-19 vaccine for adults. Mothers are much less likely to approve expedited approval. No significant changes have been found in the composition of caregivers willing to forego regulatory demands on vaccine approval.

Applications of an Equity Framework in COVID-19 Vaccine Trial and Distribution Planning.

There are a disproportionate number of cases, hospitalizations, and deaths among Black and Latinx communities, a result of a history of structural racism and exploitation. An equity framework and approach are critical but have been lacking in the COVID-19 response, including vaccine dissemination. We provide an overview and application of remove, repair, remediate, restructure, and provide (R4P), an equity framework, in examining COVID-19 vaccine trial development and related interventions. R4P is an equity framework and tool that applies critical race theory, intersectional, and dimensionality in planning, assessment, and research for creating action to eliminate inequities.

Lessons Learned from Cutting-Edge Immunoinformatics on Next-Generation COVID-19 Vaccine Research.

Presently, immunoinformatics and bioinformatics approaches are contributing actively to COVID-19 vaccine research. The first immunoinformatics-based vaccine construct against SARS-CoV-2 was published in February 2020. Following this, immunoinformatics and bioinformatics approaches have created a new direction in COVID-19 vaccine research. Several researchers have designed the next-generation COVID-19 vaccines using these approaches. Presently, immunoinformatics has accelerated immunology research immensely in the area of COVID-19. Hence, we have tried to depict the current scenario of immunoinformatics and bioinformatics in COVID-19 vaccine research. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10989-021-10254-4.

Emergency use of COVID-19 vaccines recommended by the World Health Organization (WHO) as of June 2021.

In December 2019, the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the outbreak of coronavirus disease 2019 (COVID-19), and the resulting pandemic has caused widespread health problems and social and economic disruption. Thus far in 2021, more than 4 million people worldwide have died from COVID-19, so safe and efficacious vaccines are urgently needed to restore normal economic and social activities. According to the official guidance documents of the World Health Organization (WHO), vaccines based on four major strategies including mRNA, adenoviral vectors, inactivated viruses, and recombinant proteins have entered the stage of emergency use authorization and pre-certification evaluation. The current review summarizes these vaccines and it looks ahead to the development of additional COVID-19 vaccines in the future.

3D printing technologies for in vitro vaccine testing platforms and vaccine delivery systems against infectious diseases.

Recent advances in 3D printing (3DP) and tissue engineering approaches enable the potential application of these technologies to vaccine research. Reconstituting the native tissue or cellular microenvironment will be vital for successful evaluation of pathogenicity of viral infection and screening of potential vaccines. Therefore, establishing a reliable in vitro model to study the vaccine efficiency or delivery of viral disease is important. Here, this review summarizes two major ways that tissue engineering and 3DP strategies could contribute to vaccine research: (1) 3D human tissue models to study the response to virus can be served as a testbed for new potential therapeutics. Using 3D tissue platform attempts to explore alternative options to pre-clinical animal research for evaluating vaccine candidates. (2) 3DP technologies can be applied to improve the vaccination strategies which could replace existing vaccine delivery. Controlled antigen release using carriers that are generated with biodegradable biomaterials can further enhance the efficient development of immunity as well as combination of multiple-dose vaccines into a single injection. This mini review discusses the up-to-date report of current 3D tissue/organ models for potential vaccine potency and known bioengineered vaccine delivery systems.

Enhancing glycan occupancy of soluble HIV-1 envelope trimers to mimic the native viral spike.

Artificial glycan holes on recombinant Env-based vaccines occur when a potential N-linked glycosylation site (PNGS) is under-occupied, but not on their viral counterparts. Native-like SOSIP trimers, including clinical candidates, contain such holes in the glycan shield that induce strain-specific neutralizing antibodies (NAbs) or non-NAbs. To eliminate glycan holes and mimic the glycosylation of native BG505 Env, we replace all 12 NxS sequons on BG505 SOSIP with NxT. All PNGS, except N133 and N160, are nearly fully occupied. Occupancy of the N133 site is increased by changing N133 to NxS, whereas occupancy of the N160 site is restored by reverting the nearby N156 sequon to NxS. Hence, PNGS in close proximity, such as in the N133-N137 and N156-N160 pairs, affect each other's occupancy. We further apply this approach to improve the occupancy of several Env strains. Increasing glycan occupancy should reduce off-target immune responses to vaccine antigens.

Enterotoxigenic Escherichia coli (ETEC) vaccines: Priority activities to enable product development, licensure, and global access.

Diarrhoeal disease attributable to enterotoxigenic Escherichia coli (ETEC) causes substantial morbidity and mortality predominantly in paediatric populations in low- and middle-income countries. In addition to acute illness, there is an increasing appreciation of the long-term consequences of enteric infections, including ETEC, on childhood growth and development. Provision of potable water and sanitation and appropriate clinical care for acute illness are critical to reduce the ETEC burden. However, these interventions are not always practical and may not achieve equitable and sustainable coverage. Vaccination may be the most cost-effective and equitable means of primary prevention; however, additional data are needed to accelerate the investment and guide the decision-making process for ETEC vaccines. First, to understand and quantify the ETEC disease burden, additional data are needed on the association between ETEC infection and physical and cognitive stunting as well as delayed educational attainment. Furthermore, the role of inappropriate or inadequate antibiotic treatment of ETEC-attributable diarrhoea may contribute to the development of antimicrobial resistance (AMR) and needs further elucidation. An ETEC vaccine that mitigates acute diarrhoeal illness and minimizes the longer-term disease manifestations could have significant public health impact and be a cost-effective countermeasure. Herein we review the ETEC vaccine pipeline, led by candidates compatible with the general parameters of the Preferred Product Characteristics (PPC) recently developed by the World Health Organization. Additionally, we have developed an ETEC Vaccine Development Strategy to provide a framework to underpin priority activities for researchers, funders and vaccine manufacturers, with the goal of addressing globally unmet data needs in the areas of research, product development, and policy, as well as commercialization and delivery. The strategy also aims to guide prioritization and co-ordination of the priority activities needed to minimize the timeline to licensure and use of ETEC vaccines, especially in in low- and middle-income countries, where they are most urgently needed.

Empowering Equitable Data Use Partnerships and Indigenous Data Sovereignties Amid Pandemic Genomics.

The COVID-19 pandemic has inequitably impacted Indigenous communities in the United States. In this emergency state that highlighted existing inadequacies in US government and tribal public health infrastructures, many tribal nations contracted with commercial entities and other organization types to conduct rapid diagnostic and antibody testing, often based on proprietary technologies specific to the novel pathogen. They also partnered with public-private enterprises on clinical trials to further the development of vaccines. Indigenous people contributed biological samples for assessment and, in many cases, broadly consented for indefinite use for future genomics research. A concern is that the need for crisis aid may have placed Indigenous communities in a position to forego critical review of data use agreements by tribal research governances. In effect, tribal nations were placed in the unenviable position of trading short-term public health assistance for long-term, unrestricted access to Indigenous genomes that may disempower future tribal sovereignties over community members' data. Diagnostic testing, specimen collection, and vaccine research is ongoing; thus, our aim is to outline pathways to trust that center current and future equitable relationship-building between tribal entities and public-private interests. These pathways can be utilized to increase Indigenous communities' trust of external partners and share understanding of expectations for and execution of data protections. We discuss how to navigate genomic-based data use agreements in the context of pathogen genomics. While we focus on US tribal nations, Indigenous genomic data sovereignties relate to global Indigenous nations regardless of colonial government recognition.

Pregnant women's perceptions of risks and benefits when considering participation in vaccine trials.

INTRODUCTION: Despite historical exclusion, there has been recent recognition of the need to address the health of pregnant women in research on vaccines against emerging pathogens. However, pregnant women's views and decision-making processes about vaccine research participation during infectious disease outbreaks remain underexplored. This study aims to examine women's decision-making processes around vaccine research participation during infectious disease outbreaks. METHODS: We conducted qualitative semi-structured in-depth interviews with pregnant and recently pregnant women (n = 13), eliciting their views on four hypothetical Zika Virus vaccine research scenarios and probing their decision-making processes around participation. After recorded interviews were transcribed, thematic analysis was conducted based on a priori and emergent themes. RESULTS: Most women interviewed were accepting of vaccine research scenarios. Three broad themes-evidence, risk, and trust-characterized women's decision-making processes. Women varied in how different types and levels of evidence impacted their considerations, which risks were most salient to their decision-making processes, and from whom they trusted recommendations about vaccine research participation. Exemplary quotes from each theme are presented, and lessons for vaccine development during the current COVID-19 pandemic and future outbreaks are discussed. CONCLUSION: Some pregnant women are accepting of participation in vaccine research during infectious disease outbreaks. Incorporating their priorities into trial design may facilitate their participation and generation of evidence for this important population.