An injection of hope: the questions that remain for a COVID-19 vaccine

So begins a piece by The Daily Mail’s science correspondent Victoria Allen this week accompanied by images of the highly technical steps, shrouded in protective gear and dry ice fog, involved in manufacturing and transporting the COVID-19 vaccine candidate BNT162b2 from BioNTech’s bioreactor in Mainz, Germany, to Pfizer’s factory in Puurs, Belgium, and into temperature controlled crates ready for shipping. While trials to establish the safety and efficacy of vaccines are ongoing, companies including Pfizer have begun large scale production "at risk" so that millions of doses could be ready when the results are in.

Getting to this point has been an extraordinary scientific journey, and making this vaccine available to the UK public, if it’s approved, will continue to demand extraordinary efforts: scaling up manufacturing faster than ever; getting doses through the NHS supply chain at ultra-low temperatures (described by Chief Executive of the Bioindustry Association Steve Bates as “new territory”); and a huge operation to offer a vaccine through the NHS. Matt Hancock said in the House of Commons on 10 November that “the logistics are complex, the uncertainties are real, and the scale of the job is vast”, requiring already hard pushed frontline NHS staff to work long days and weekends. Nevertheless, he maintained, “I know that they will rise to this challenge of being ready when the science comes good to inject hope into millions of arms this winter.”

So optimism seems to be the key message, though uncertainty remains a key word. The findings presented by Pfizer and BioNTech this week represent a preliminary analysis, part of the research process intended to work out whether continuing a study is worthwhile. With a 90 per cent efficacy rate and “no serious safety concerns” so far that seems a given, but there is still more to discover. Pfizer’s trial protocol dictates that before the study can conclude, it must reach at least 164 cases of COVID-19 among study participants to compare the performance of the vaccine in vaccinated individuals to those who received a placebo. So far there have only been 94 cases and the efficacy rate could go down, or up, as it moves towards that target. No data from the study have yet been published or peer reviewed.

Regulators in the UK and elsewhere will want to see more certainty about the efficacy, quality and safety of current vaccine candidates before anything but hope is injected at a larger scale, though some have indicated that they are ready to allow ‘emergency use’ under particular conditions before the trials have formally concluded. In the US, the FDA will consider such a temporary approval once data on safety is available from half of the trial participants two months after the final dose of the vaccine, which according to Pfizer’s estimates might happen by the third week of November. The UK’s Medicines and Healthcare products Regulatory Agency (MHRA) has reportedly begun a rolling review of the Pfizer/ BioNTech vaccine alongside other candidates such as that developed by AstraZeneca and the University of Oxford. New law has come into force to allow the MHRA to authorise a temporary supply for vaccines before 2021, when Brexit will mean the UK can make decisions independently of the European Medicines Agency. When recently questioned as part of the parliamentary Coronavirus: lessons learnt joint inquiry, the Chair of the UK’s Vaccine Taskforce Kate Bingham said that as a natural optimist, she took the rose-tinted view that vaccine deployment could begin in the UK by year end.

But even if regulators decide the evidence backs an emergency authorisation, clinical trials will go on and some uncertainty will not be resolved until a vaccine has been given to a wider population. Questions that remain include: whether the vaccine protects against infection and transmission of COVID-19 or just prevents serious disease in those who are infected; and how long the protection offered by the vaccine lasts, as well as the longer term safety of the vaccine itself. It will be important to establish how well the vaccine performs in different groups – while the companies say the study has included participants with diverse ethnic backgrounds there is not yet any data available on performance in different age groups. A recent study of exclusion criteria across a range of stage 3 vaccine and drug trials for COVID-19 found that a range of criteria meant older adults were likely to be excluded from all vaccine trials, despite being the group most vulnerable to COVID-19 disease.

The answers to these questions will be important in informing the government’s strategy for allocating vaccine doses which will initially be limited whichever candidate might get approval for use. The Joint Committee on Vaccination and Immunisation (JCVI), which advises UK health departments on immunisation, has issued interim advice to inform a future strategy for distributing vaccines, which proposes a priority ranking of groups starting with care workers and care home residents. However, it is not clear how closely this guidance will be followed in practice. Other advisory bodies have taken slightly different approaches. For example, the National Academies of Sciences, Engineering and Medicine in the US have recommended first prioritising high risk health workers and first responders, people of all ages with comorbid and underlying conditions that put them at significantly higher risk and older adults living in congregate or overcrowded settings. The European Centre for Disease Prevention and Control (ECDC) proposes a range of possible approaches such as targeting groups with an increased risk of exposure and onward transmission of SARS-CoV-2, prioritising geographical regions with high incidence of COVID-19, or deploying the vaccine to control active outbreaks.

The Council’s latest spotlight briefing note on questions on the UK’s COVID-19 response highlights issues that could affect public confidence and by extension the uptake of any vaccine. In particular it points to how the processes involved in getting a vaccine ready for use might be perceived, be it the accelerated scientific and manufacturing processes, negotiations to secure vaccine doses, or changes in UK regulation aimed at speeding up approval. Failure to communicate clearly about how and why this has been in the public interest might fuel scepticism and leave gaps for misinformation already circulating on social media.

This matters, not least because, as highlighted by a new review by the Royal Society and the British Academy, it is not having the vaccine but vaccination that saves lives. Clearly concerned about this, the Government has agreed a package of measures with Google, Twitter and Facebook to tackle misinformation about vaccines on their platforms. However, gaining trust across the population is likely to require more than this. The Council has repeatedly stressed the need for open deliberation around the public health measures imposed to address COVID-19. Questions such as how different values, interests and risks are being balanced, and what interests take priority and why, could reasonably be asked about, for example, how vaccines will be allocated, or whether the Government is considering approaches such as incentivised or even mandatory vaccination programmes, and whether such approaches could be ethically justifiable. With the prospect of a vaccine becoming available in the near future, these questions need to be consciously and transparently addressed, in an inclusive and public fashion.

We are working on a briefing note on vaccine confidence, to be published next year.