Podcast Review: Macro Hive Conversations With Prof. Justin Stebbing

Introduction

Following last week’s vaccine news from Pfizer, we welcomed Professor Justin Stebbing back onto our podcast show. We first interviewed Justin in July, when he argued that we could see a COVID-19 vaccine around US election time. He was right, and so we wanted to get his latest views. This time, he explains what to expect over the next few months (including Moderna’s results) and what key uncertainties remain.

The Vaccine News We’ve All Been Waiting For

On 9 November, Pfizer and BioNTech (PFE/BNTX henceforth) released a brief press release announcing the first interim analysis of its phase three vaccine trial. The study enrolled 43,538 global participants, from which 94 confirmed COVID-19 patients were evaluated (also known as ‘events’). The analysis showed 90% efficacy.

‘The world had a very good day’, Justin emphasises throughout the interview. A typical viral vaccine takes as many as 10 years to manufacture and produces efficacy results between 85-90%. The PFE/BNTX candidate covers a large number of participants, including a significant proportion from racially and ethnically diverse backgrounds, and it shows no signs of strange toxicity data.

He is equally as optimistic around the results of the other two main vaccine manufacturers – Moderna and AstraZeneca & University of Oxford (AZN/Oxford henceforth). He expected the former to announce initial findings in November (which they have done today) and the latter to present interim analysis before the end of the year. In total, these three trials will cover over 100,000 patients, 500 COVID events and provide 6bn doses by 2021.

The World Will Reopen Sooner Than We Think

The Imperial College London professor says there is now ‘room for more-than-cautious optimism that, by next summer, we will be able to go on holidays…and it’ll be safe to meet people’. Pressed for a date, he suggests that such a high vaccine efficacy might mean that coronavirus cases could fall sharply by Q2 2021.

His views are based on a herd immunity estimate of 40% and the fact that 15% of the global population have likely had the virus. This means that just 25% of the population will require vaccination. With plans to produce as many as 14.5bn vaccine doses between the three main developers (PFE/BNTX, Moderna, and AZN/Oxford) by 2022, this figure is soon attainable.

Cold-Chain Distributional Issues Are Solvable

This week, Pfizer is expected to file an emergency authorisation to the Food and Drug Administration. The FDA should then meet in December to (most likely) approve not only the PFE/BNTX vaccine, but the Moderna (the results of which he expected to be announced soon) and AZN/Oxford vaccines too. The next part of the process will be distribution.

One major impediment appears to be the very low temperatures at which the vaccines need to be stored. Justin believes that this is surmountable, however. ‘The hardest hurdles [i.e. organising very complicated trials] have been overcome. Sorting out cold-chain distributional issues should be achievable in a very short space of time’.

In rolling out the vaccine, PFE/BNTX will be using FedEx. By 2021, Pfizer is expected to deliver around 500mn doses to the US, 300mn to the EU, 120mn to Japan and 30-40mn to the UK (10mn by end of 2020!).

How Does the Vaccine Work, and How Long Will It Last?

There are approximately 300 candidate vaccines. The effectiveness of each will likely be unique to the characteristics (e.g. age and ethnicity) of individual patients. Pfizer is yet to announce the details of their trial, but we do know the vaccine candidate requires two doses 21 days apart. Each dose invokes both an antibody and T-cell response that will take at least two to three weeks to kick in.

The T-cell and B-cell responses are important for the long-term durability of a vaccine. Studies on immunity have shown varying and declining degrees of antibody resistance over time. The most important aspect, Justin explains, is instead whether the T-cell and B-cell responses persist. It is estimated that these cells have a prolonged presence five or more months post infection, and so a vaccine probably provides protective immunity for potentially six to 12 months, or longer.

Interestingly, Justin is not particularly worried about Danish mink farms impacting the durability of the vaccine. In general, the virus does not mutate much, but studies appear to show that the Danish mutation makes it less ‘fit’ and less transmittable.

Key Uncertainties Remain

On uptake, anti-vaxxer movements have been particularly high profile. Professor Stebbing believes that it should be the FDA’s priority to ‘win the hearts and minds’ of people. This will require greater transparency from manufacturers. Justin is hopeful, however, that around 65% uptake should be achievable given the lure of individual freedom associated with protective immunity. He does not rule out the possibility of government vaccine mandates.

There are also uncertainties around vaccine trial details that are yet to be published. One of the main unanswered questions is how effective they are for older patients. ‘Different vaccines may be better for different groups’, Justin stresses. On this front, expect full peer reviews to come out in the next month.

On a similar note, there is a need for a wide variety of vaccines. While the three main vaccine manufacturers have been able to organise large-scale trials, smaller companies will struggle to obtain good candidates. This problem will only worsen once vaccines are released and COVID transmission begins to fall.

With fewer available vaccines, ‘vaccine nationalism’ may become an issue. Justin explains that, while having the WHO, Covax and CEPI to look after the developing world is a good thing, it is inevitable that some vaccine manufacturers will favour particular countries. For example, the US government has provided over $1bn worth of funding for Moderna and AZN/Oxford vaccines.

Other Highlights From Our Conversation

Professor Stebbing aptly puts into context the importance of a vaccine. Positivity rates in some American states are in the high single digits, mortality rates among people with active cancer and COVID is 22%, long COVID may lead to a wave of heart failures in young individuals, and the range of suffering for elderly patients is unparalleled with any other viral infection.

We also talk about the toolkit Asian countries possess for controlling the virus and the challenges the UK government faces with issues around civil liberties. Lastly, he mentions the risks associated with students going home for Christmas and the two-way risks governments and vaccine manufacturers alike have had to overcome when considering the future.