Human challenge studies in the study of infectious diseases
What can deliberately infecting healthy people tell us about infectious diseases? How is this useful for developing treatments, and how do we manage the risks?
The UK Government secured early access to 340 million doses of six different COVID-19 vaccine candidates. It is still unknown whether any of them will be able to protect from SARS-CoV-2. In case of a successful vaccine candidate, supply may be initially constrained and therefore priority groups need to be defined.
Several COVID-19 vaccine candidates are currently in clinical trials around the world. As of 24 August 2020, the UK Government secured early access to a total of at least 340m doses of six different vaccine candidates, if proven successful. The selected candidates are based on different vaccine technologies:
Investing in a wide portfolio of vaccine candidates is important because it is still unknown which candidate (if any) will confer protection from SARS-CoV-2, and whether certain candidates would work better for specific groups, such as the elderly. Including the elderly, pregnant women and participants with chronic conditions in clinical trials are among the WHO criteria for COVID-19 vaccine prioritisation.
Even if one of the six vaccine candidates secured by the UK is successful, enough doses for the entire population will not all be available initially. Therefore priority groups for vaccination need to be identified.
On 7 May, the Joint Committee on Vaccination and Immunisation (JCVI), an independent Departmental Expert Committee and statutory body, held an extraordinary meeting on COVID-19 immunisation prioritisation. On 18 June, the JCVI published interim advice on priority groups for vaccination. They advised priority vaccination of frontline health and social care workers and those at “increased risk of serious disease and death from COVID-19 infection stratified according to age and risk factor”. There is ongoing work to refine who belongs to this last group. The Committee will review the composition and order of priority groups for vaccination as evidence emerges.
Evidence collected so far indicates that those at greatest risk of severe illness and mortality from COVID-19 in the UK are adults aged 50 years and above (with the risk increasing with age) and those suffering from chronic diseases (such as chronic heart disease, kidney disease or lung disease, cancer, obesity, and dementia). In its guidance on shielding and protecting people who are clinically extremely vulnerable from COVID-19, Public Health England considers people such as transplant recipients, or with specific cancers, severe respiratory conditions, on immunosuppressive therapies, and pregnant women with significant heart disease to be at greatest risk of severe COVID-19.
On 6 July, the JCVI held another extraordinary meeting on COVID-19 Immunisation prioritisation. They explored, among other topics, the need to further stratify priority groups in case of limited vaccine supply and how to best coordinate a potential COVID-19 vaccination programme with the 2020–2021 influenza vaccination programme. They agreed that the two groups identified in the JCVI interim statement are still considered to be the highest priority until more information on successful COVID-19 vaccines is available. These groups partially overlap with the priority groups identified by the WHO Global Allocation Framework: healthcare workers, adults over 65 years of age, and adults with illnesses such as cardiovascular disease, cancer, diabetes, obesity or chronic respiratory disease.
In case of a successful COVID-19 vaccine, there will be demand from all countries around the world, but not all of them may be able to afford it.
At the end of April, the WHO and other global partners launched the Access to COVID-19 Tools (ACT) Accelerator, a global collaboration to accelerate development, production and equitable access to resources to fight COVID-19. The ACT Accelerator is organised into four pillars of work: diagnostics, treatment, vaccines and health system strengthening. The vaccine pillar (COVAX) is led by the WHO, the Coalition for Epidemic Preparedness Innovations (CEPI) and Gavi, the Vaccine Alliance. COVAX is the pillar requiring the highest investment, equal to USD$18.1 billion in 18 months. Its goal is to procure 2 billion doses of COVID-19 vaccines by the end of 2021 through the COVAX Facility. Priority populations likely to be first considered by COVAX are healthcare workers (1% of the global population), adults aged over 65 years (8% of the global population) and high-risk adults with underlying conditions, such as hypertension or diabetes (15% of the global population). In early June, Gavi launched the COVAX Advance Market Commitment (AMC), a financing mechanism to support affordable vaccine access for developing countries. COVAX AMC, inspired by a previous highly successful Advance Market Commitment programme for pneumococcal vaccines, was the first step to create the COVAX Facility. 92 low- and middle-income countries will be able to access COVID-19 vaccines through this initiative.
In August, CEPI published the findings from a survey assessing potential COVID-19 vaccine manufacturing capacity across 113 manufacturers around the world. It revealed a potential global capacity to produce at least 2–4 billion doses of COVID-19 vaccine through to the end of 2021, in line with COVAX objectives.
Ensuring global and equitable access to a COVID-19 vaccine in the midst of a pandemic without a cure is a complex task. At the end of May, the Nuffield Council on Bioethics published a policy briefing on the key challenges for ensuring fair and equitable access to COVID-19 vaccines and treatments. Pricing, limited supplies, health inequalities and vulnerable groups, public trust and fair resource allocation were among the factors identified as barriers to fair and equitable access. In early June, Médecins Sans Frontières recommended that world leaders require pharmaceutical companies to sell COVID-19 vaccines at–cost, to follow a transparent and objective global allocation system, and to hold each other to account. Later in June, several organisations signed an open letter to Gavi Board Members to ask for changes to the COVAX Facility design to ensure access to COVID-19 vaccines for all. These include allocation of vaccines upon public health criteria for all countries, transparency, at–cost prices and accountability.
Global access and distribution of COVID-19 vaccines has been widely discussed in the UK Parliament and identified as one of the immediate aims of the UK Vaccine Taskforce, the group set up in April by the UK Government to coordinate rapid development and production of COVID-19 vaccines. A Wellcome Trust report on public views about global access to COVID-19 treatments and vaccines found that nine in ten (90%) of UK respondents agreed that coronavirus treatments and vaccines should first be provided for those who need them most in the world. The UK, who has pledged £250m to CEPI in May, is among the 81 potentially self-financing countries expressing interest in the COVAX Facility, which will include at least 136 countries in total.
At the beginning of May, the European Commission launched the Coronavirus Global Response, an initiative to promote global access to affordable COVID-19 vaccination, treatment and testing that has raised a total of €15.9 billion to date. In the EU Strategy for COVID-19 vaccines, one of the main objectives is ensuring equitable access for everyone in EU member states to an affordable vaccine as early as possible. Many EU countries expressed interest in joining the COVAX Facility, and in July the European Commission co-funded, with €100 million, a call from CEPI to support the rapid development and global manufacture of COVID-19 vaccines.
In February, the United States Agency for International Development (USAID) pledged $1.16 billion in funding for Gavi’s immunisation programmes between 2020 and 2023. However, the US does not appear in the publicly available list of potentially self-financing countries expressing interest in the COVAX Facility. Early in August, the US Secretary of Health and Human Services said that any US vaccine or treatment for COVID-19 would be shared with other countries only after the US need has been met.
At the beginning of August, the WHO urged other rich countries to join COVAX AMC, as it only raised $600m in July, against its initial target of USD$2 billion.
Recent surveys have examined the general public’s attitudes towards a COVID-19 vaccine in the UK:
The WHO indicated vaccine hesitancy – a delay in acceptance or refusal of vaccines despite their availability – to be one of the top ten threats to global health in 2019. The Wellcome Global Monitor 2018 found that 9% of UK survey respondents strongly or somewhat disagreed that vaccines are safe and 3% of them strongly or somewhat disagreed that vaccines are effective.
According to a recent CCDH report, anti-vaxxers are a growing threat to COVID-19 vaccines and the largest anti-vaxxer accounts on social media have gained at least 7.8 million followers (corresponding to a 19% increase) since 2019. Scientists have raised concerns about the role of anti-vaxxers in promoting messages against COVID-19 vaccines. A recent report by the Organisation for Economic Co-operation and Development (OECD) identifies COVID-19 disinformation on online platforms as a threat for vaccine uptake that could put at risk the efforts to overcome the pandemic. They highlighted solutions to tackle disinformation, such as supporting independent fact-checking, ensuring the presence of human moderators, issuing transparency reports and improving users’ literacy skills in media, digital and health.
What can deliberately infecting healthy people tell us about infectious diseases? How is this useful for developing treatments, and how do we manage the risks?
How do our bodies defend against Covid-19? Read how immune responses differ across people, variants, reinfection, vaccination, and current immunisation strategies.
Research studies involving thousands of people have allowed scientists to test which drugs are effective at treating COVID-19. Several drug therapies are now available to treat people who are in hospital with COVID-19, or to prevent infections in vulnerable people becoming more serious. This briefing explains which drugs are available, the groups of people in which they are used and how they work. It also outlines the importance of monitoring the emergence of new variants and drug resistance.