Shifts in UNAIDS ethics guidance and implications for ethics review of preventive HIV vaccine trials.

INTRODUCTION: A major change in the ethics framework for preventive HIV vaccine trials worldwide is the release of the UNAIDS 2021 ethical considerations in HIV prevention trials. This new guidance comes at an exciting time when there are multiple HIV vaccine efficacy trials in the field. Research Ethics Committees (RECs) or Institutional Review Boards are a most likely audience for these guidelines. Our objective is to highlight shifts in ethics recommendations from the earlier 2012 UNAIDS guidance. DISCUSSION: We review recommendations related to four key issues, namely standard of prevention, post-trial access to safe and effective vaccines, enrolment of adolescents and enrolment of pregnant women. We outline implications and make recommendations for the ethics review process, including suggested lines of inquiry by RECs and responses by applicants. CONCLUSIONS: There have been several shifts in the UNAIDS ethics guidance with implications for HIV vaccine researchers submitting applications for initial ethics review or re-certification, and for RECs conducting such reviews. This review may assist RECs in a more efficient and consistent application of ethics recommendations. However, additional tools and training may further help stakeholders comply with new UNAIDS ethics recommendations during protocol development and ethics review

Promoting ethics and integrity in research and innovation for development in Africa : the role of Africa’s science granting councils : a discussion paper prepared for the Science Granting Councils Initiative (SGCI) master class of 2021

The paper advocates for Science Granting Councils (SGC) to enhance ethics and integrity activities as part of their responsibilities for supporting ethical conduct of research and innovation. SGCs should play a leading role in facilitating development of, or revision of research policies to ensure that ethics and integrity issues are addressed satisfactorily. The African science enterprise through SGCs, needs to adapt to growing concerns if it is to remain relevant. The paper provides an in- depth report of current and existing challenges within the purview of the Science Granting Councils, which was provided to SGCs from 15 participating African countries at the SGCI Masterclass event

Strengthening the role of African Science Granting Councils in promoting ethics and integrity in research and innovation

“Ethics and Integrity in Research and Innovation in Development” was the theme of the 2020 Science Granting Council’s (SGC) Masterclass. African SGCs need to enhance their activities and roles as part of their responsibilities in supporting ethical conduct of research and innovation. The African science enterprise through SGCs, needs to adapt to growing concerns if it is to remain relevant. SGCs should play a leading role in facilitating development of, or revision of research policies to ensure that ethics and integrity issues are addressed satisfactorily. This policy brief is a response to the growth in research being conducted in African countries.United Kingdom’s Foreign, Commonwealth and Development Office (FCDO)Swedish International Development Cooperation Agency (Sida)South African’s National Research Foundation (NRF)German Research Foundation (DFG

Research ethics capacity building in Sub-Saharan Africa: a review of NIH Fogarty-funded programs 2000–2012

The last fifteen years have witnessed a significant increase in investment in research ethics capacity development throughout the world. We examine nine research ethics training programs that are focused on Sub-Saharan Africa and supported by the US National Institutes of Health. We collected data from grants awards' documents and annual reports supplemented by questionnaires completed by the training program directors. Together, these programs provided long-term training in research ethics to 275 African professionals, strengthened research ethics committees in 19 countries in Sub-Saharan Africa, and created research ethics curricula at many institutions and bioethics centers within Africa. Trainees' leadership resulted in new national systems and policies on research ethics, human tissue storage and export, and methods of monitoring compliance with research ethics guidelines. Training programs adapted to challenges that arose due to varied trainees' background knowledge in ethics, duration of time available for training, spoken and written English language skills, administrative obstacles, and the need to sustain post-training research ethics activities. Our report showcases the development of awareness of research ethics and building/strengthening of basic research ethics infrastructure in Sub-Saharan Africa. Nevertheless, the increasing amount and complexity of health research being conducted in Sub-Saharan Africa suggests the need for continued investment in research ethics capacity development in this region. This paper is part of a collection of papers analyzing the Fogarty International Center's International Research Ethics Education and Curriculum Development program

Ethical Considerations for International Recruitment in COVID-19 Human Challenge Trials

Ongoing and anticipated COVID-19 human challenge studies in the UK may advance our understanding of COVID-19 and facilitate the licensure of safe, effective, and easily deployable next-generation COVID-19 vaccines and boosters. We argue that international volunteer recruitment for COVID-19 human challenge trials can help promote diversity in these trials and ensure a sufficient number of eligible volunteers, both of which will increase the benefits of challenge research. We explore the ethical ramifications of dealing with unfair background conditions of global vaccine injustice to expand medical research, and conclude that international recruitment for COVID-19 human challenge trials can be conducted ethically provided that several robust protections are in place for volunteers

Aberrantly Expressed Genes in HaCaT Keratinocytes Chronically Exposed to Arsenic Trioxide

Inorganic arsenic is a known environmental toxicant and carcinogen of global public health concern. Arsenic is genotoxic and cytotoxic to human keratinocytes. However, the biological pathways perturbed in keratinocytes by low chronic dose inorganic arsenic are not completely understood. The objective of the investigation was to discover the mechanism of arsenic carcinogenicity in human epidermal keratinocytes. We hypothesize that a combined strategy of DNA microarray, qRT-PCR and gene function annotation will identify aberrantly expressed genes in HaCaT keratinocyte cell line after chronic treatment with arsenic trioxide. Microarray data analysis identified 14 up-regulated genes and 21 down-regulated genes in response to arsenic trioxide. The expression of 4 up-regulated genes and 1 down-regulated gene were confirmed by qRT-PCR. The up-regulated genes were AKR1C3 (Aldo-Keto Reductase family 1, member C3), IGFL1 (Insulin Growth Factor-Like family member 1), IL1R2 (Interleukin 1 Receptor, type 2), and TNFSF18 (Tumor Necrosis Factor [ligand] SuperFamily, member 18) and down-regulated gene was RGS2 (Regulator of G-protein Signaling 2). The observed over expression of TNFSF18 (167 fold) coupled with moderate expression of IGFL1 (3.1 fold), IL1R2 (5.9 fold) and AKR1C3 (9.2 fold) with a decreased RGS2 (2.0 fold) suggests that chronic arsenic exposure could produce sustained levels of TNF with modulation by an IL-1 analogue resulting in chronic immunologic insult. A concomitant decrease in growth inhibiting gene (RGS2) and increase in AKR1C3 may contribute to chronic inflammation leading to metaplasia, which may eventually lead to carcinogenicity in the skin keratinocytes. Also, increased expression of IGFL1 may trigger cancer development and progression in HaCaT keratinocytes

Arsenic Trioxide Modulates DNA Synthesis and Apoptosis in Lung Carcinoma Cells

Arsenic trioxide, the trade name Trisenox, is a drug used to treat acute promyleocytic leukemia (APL). Studies have demonstrated that arsenic trioxide slows cancer cells growth. Although arsenic influences numerous signal-transduction pathways, cell-cycle progression, and/or apoptosis, its apoptotic mechanisms are complex and not entirely delineated. The primary objective of this research was to evaluate the effects of arsenic trioxide on DNA synthesis and to determine whether arsenic-induced apoptosis is mediated via caspase activation, p38 mitogen–activated protein kinase (MAPK), and cell cycle arrest. To achieve this goal, lung cancer cells (A549) were exposed to various concentrations (0, 2, 4, 6, 8, and 10 μg/mL) of arsenic trioxide for 48 h. The effect of arsenic trioxide on DNA synthesis was determined by the [3H]thymidine incorporation assay. Apoptosis was determined by the caspase-3 fluorescein isothiocyanate (FITC) assay, p38 MAP kinase activity was determined by an immunoblot assay, and cell-cycle analysis was evaluated by the propidium iodide assay. The [3H]thymidine-incorporation assay revealed a dose-related cytotoxic response at high levels of exposure. Furthermore, arsenic trioxide modulated caspase 3 activity and induced p38 MAP kinase activation in A549 cells. However, cell-cycle studies showed no statistically significant differences in DNA content at subG1 check point between control and arsenic trioxide treated cells

The Structure and Function of Research Ethics Committees in Africa: A Case Study

Kass and colleagues explore the strengths and weaknesses of research ethics committees in Africa

Estrogenic Activity of Coumestrol, DDT, and TCDD in Human Cervical Cancer Cells

Endogenous estrogens have dramatic and differential effects on classical endocrine organ and proliferation. Xenoestrogens are environmental estrogens that have endocrine impact, acting as both estrogen agonists and antagonists, but whose effects are not well characterized. In this investigation we sought to delineate effects of xenoestrogens. Using human cervical cancer cells (HeLa cells) as a model, the effects of representative xenoestrogens (Coumestrol-a phytoestrogen, tetrachlorodioxin (TCDD)-a herbicide and DDT-a pesticide) on proliferation, cell cycle, and apoptosis were examined. These xenoestrogens and estrogen inhibited the proliferation of Hela cells in a dose dependent manner from 20 to 120 nM suggesting, that 17-β-estrtadiol and xenoestrogens induced cytotoxic effects. Coumestrol produced accumulation of HeLa cells in G2/M phase, and subsequently induced apoptosis. Similar effects were observed in estrogen treated cells. These changes were associated with suppressed bcl-2 protein and augmented Cyclins A and D proteins. DDT and TCDD exposure did not induce apoptosis. These preliminary data taken together, suggest that xenoestrogens have direct, compound-specific effects on HeLa cells. This study further enhances our understanding of environmental modulation of cervical cancer