7 August 2020

The race for a Covid-19 cure could still have a long way to run

By Professor Angus Dalgleish

News that the Oxford covid vaccine candidate induced strong immune responses has led to renewed hope that we may have a vaccine – either to stem the spread of the virus or reduce the severity of the disease – some time soon. However, as with nearly anything coronavirus-related, there are several issues which are far from clear.

Firstly, like all the other attempts to make a Covid vaccine, the Oxford team have chosen to use the spike protein which sticks up from the cell surface of the virus as the main target, and to induce a strong neutralising antibody response. However, it now appears that antibodies do not seem to last long in naturally infected people, with the majority showing no evidence at all of antibodies after only a few months.

Secondly, there is a growing recognition that the response of T cells (which essentially seek and destroy infected cells) may be more important in controlling this virus than antibodies (infection fighting proteins produced by immune cells) – and that to harness this effectively requires a strong T cell adjuvant (a pharmacological boost). Interestingly, the current trials are reporting the presence of T cell responses as well as antibodies.

In late March, I reported in The Telegraph that cancer patients on a non-specific vaccine (IMM-101, which boosts the failing T cell response seen in cancer patients and which fades from age 55 onwards, all remarked how amazed they were that they no longer suffered from colds and flu.

I noted that this fitted in with the growing suspicion that the old TB vaccine, BCG, seemed to confer some protection from Covid-19 infection and death rates – something recently confirmed by an academic paper.

Following my article, it was proposed that the UK support a trial of front-line workers, who at that stage were starting to die from their infections.

However, the Chief Medical Officer and SAGE felt the treatment required more animal testing (which caused some surprise amongst my flu-free patients). Luckily, the article attracted the attention of the Canadian healthcare authorities, who had been looking at the possibility of using BCG for this purpose for a while. However, they were aware of several limitations of using BCG as a therapeutic for at-risk people, since it is an attenuated virus. They realised that the IMM-101 was a far superior candidate for a vaccine, since it is designed to boost the non-specific T cells that ward off new unseen dangerous viruses. After much due diligence, the Canadian government have agreed to sponsor a large study of thousands of Canadians  which could quickly capture IMM-101’s efficacy against Covid.

But it’s not just the hope of future trials we should be leaning on – lessons can keep being drawn from the past.

Many years ago my Norwegian collaborator Birger Sorenson and I both predicted that all HIV vaccines then in trial would fail – and unfortunately, we were proven right. Why did we think that? Well, we believed that using the whole of the HIV envelope (a membrane that forms the outermost layer of the virus) would induce too strong and varied an immune response, and act as a decoy which would blind the immune system from seeing the Achilles Heel of the virus – and therefore it would not be effective.

Sorenson and I applied this insight to the Covid-19 vaccine challenge and realised that the virus’ protein spike was even worse than the HIV envelope since it would induce a strong antibody response – which we now know from recent HIV research will drown out T cell responses.

Our concern is that if the HIV story is repeated then more people will get infected as new or trial vaccines are rolled out, and this phenomenon will be much worse in people with declining T cell responses – namely the elderly, just the population that will need to be protected. It is worth noting that the Oxford study which sparked such hope was a study of healthy people with an average age of 35 who should not, therefore, experience side effects or adversity on exposure, unlike those with weaker immune systems.

Thankfully, the Canadian study will also include elderly patients and those with compromised immune systems, and is going to capture whether IMM-101 prevents all other infections not just Covid-19.

Depending on the real world results of the 155 Covid-19 vaccines in development, all of which include targeting the spike, we will soon know if the secret of an effective vaccine is not what you put into it, but what bits you leave out.

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Professor Angus Dalgleish is a Professor of Oncology at St Georges and a Fellow at the Centre for Brexit Policy

Columns are the author's own opinion and do not necessarily reflect the views of CapX.