WHO has listed several priority diseases with epidemic potential for which there are no, or insufficient, medical countermeasures. In response, the Bill & Melinda Gates Foundation (with support from PricewaterhouseCoopers) coordinated subject matter experts to create a preparedness plan for Disease X. Disease X is caused by Pathogen X, an infectious agent that is not currently known to cause human disease, but an aetiologic agent of a future outbreak with epidemic or pandemic potential. We have identified crucial areas for acceleration in medical countermeasure product development and international coordination. We have also reviewed novel platforms and process improvements related to manufacturing, which could revolutionise the response to the next pandemic. Finally, we created several coordination and engagement guides. These guides range from the rational design of an intervention target product profile, to the key facets of vaccine and therapeutic development, to accelerated manufacturing and regulatory mechanisms. In this Personal View, we provide a high-level summary of the outcomes of the medical countermeasure development workstream, intended for a broad audience including academia, medical countermeasure developers, and multilateral coordinating bodies. We hope that they might find this piece useful in prioritising strategic investments and efforts to accelerate medical countermeasure development. We observed that in-depth analyses of clinical trial design, chemistry, manufacturing and control activities, and accelerated regulatory pathways are necessary for shortening the timelines for the product development of medical countermeasures. We intend to cover these topics in future publications.

In 2018, the Bill and Melinda Gates Foundation convened over thirty subject matter experts in clinical development, manufacturing, and regulatory assessment to determine how the development and approval of medical countermeasures could be accelerated in the event of Disease X. Disease X is the result of a presently unknown pathogen with epidemic or pandemic potential. A key opportunity to accelerate the scientific assessment and regulatory approval of medical countermeasures exists within efficient navigation of facilitated regulatory pathways. It was identified that not all stakeholders will be able to skillfully navigate the facilitated pathways offered by the various regulatory agencies during a public health emergency. To democratize this knowledge, we have written an overview of the facilitated approaches which have been developed and refined by Stringent Regulatory Authorities and the World Health Organization for the primary assessment of medical products. We discuss the conditions necessary for use of these approaches, scenarios in which certain pathways may be applicable, and the pros and cons of these approaches. We also address opportunities available to developers in, or developers who wish to access, low-income countries that may have nascent regulatory frameworks.

Sickle cell disease is caused by inherited mutations of the globin gene, and is a multisystem disorder characterised by distortion, stiffness, and adhesion of red blood cells. Every year in Africa, around 230 000 children are born with sickle cell disease and about 90% of them could die before the age of 5. At around 1 year of age, these children begin to have anaemia, pain, stroke, retinopathy, and chronic damage affecting the spleen, lungs, kidney, and major joints. They become particularly susceptible to infection-pneumococcal sepsis is the leading cause of death. Nigeria and Democratic Republic of the Congo bear the majority of Africa's sickle cell disease burden. 1 Sadly, these child mortality figures are a gross underestimation of the sickle cell disease burden, and do not consider the intersection of sickle cell disease with infectious disease, immunisation, and mental and maternal health, as well as the impact of sickle cell disease on attainment of the Sustainable Development Goals of ending poverty and reducing inequality.Sickle cell disease can be caused by multiple genetic variants. Most estimates of sickle cell disease burden account only for the homozygous HbSS variant, which excludes mortality and morbidity caused by the HbSC variant or thalassaemia. Inclusion of HbSC and thalassaemia would add a further 130 000 children born with severe haemoglobinopathies annually to global estimates. Additionally, pregnancy is a life-threatening complication of sickle cell disease. In low-resource countries, pregnancy in women with sickle cell disease is associated with 22-times the risk of death. 2 Notably,

A new oral polio vaccine, nOPV2, has become the first vaccine to pursue a WHO Emergency Use Listing. Many lessons were learned as part of the accelerated development plan and submission, which have been categorized under the following sections: regulatory, clinical development, chemistry manufacturing and controls, and post-deployment monitoring. Efforts were made to adapt findings from these studies to COVID-19 vaccine candidates. Specific concepts for accelerating COVID-19 vaccine development across multiple functional domains were also included. The goals of this effort were twofold: (1) to help familiarize vaccine developers with the EUL process; and (2) to provide general guidance for faster development and preparations for launch during the COVID-19 pandemic.

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Host restriction factors mount a first line response to viral infection, yet, are often hampered by specific viral proteins which directly resist their action. The HIV-2 proteins gag, vif, env, and vpx serve to modify the actions of four major host restriction factors: TRIM5a, APOBEC, Tetherin, and SAMHD1, respectively. The HIV-2 proteins utilise no specific enzymatic function in their roles as antagonists, but rather act as "linker molecules"; connecting host restriction factors to the proteins of cellular pathways that facilitate their sequestration or degradation, and in so doing-enabling viral replication and transmission. This article explores the complex interplay between the host restriction factor and the HIV-2 protein antagonist.

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