End of the production line for the vaccines whose job is done

They saved millions of lives but time is up for jabs such as Astrazeneca’s as the WHO advise pharma to target the Omicron virus, writes Helen Mcardle

IT WAS the first vaccine administered anywhere in the world against Covid but this week Astrazeneca announced that it is withdrawing the product from markets worldwide.

The decision comes days after it emerged that the pharmaceutical giant had admitted in legal documents that the jag “can, in very rare cases” cause Thrombosis with Thrombocytopenia Syndrome (TTS), a serious and potentially fatal blood clotting complication which had never been seen before.

The company itself, and many scientists, have insisted that the two events are not linked, and in many respects it makes sense to cease manufacturing a vaccine that has been steadily overtaken by more adaptable MRNA brands as the virus has evolved and mutated.

In April, the World Health Organisation issued updated guidance advising that formulations for Covid vaccines should target the newer JN.1 strains of Omicron which are displacing the previously dominant XBB lineages.

Astrazeneca conceded that demand for its vaccine had dwindled and it was left with surplus supplies.

It uses a more traditional viral-vector mechanism and has never been updated beyond the original “Wuhan” variant, which means that, over time, its ability to protect against infection and serious illness will have eroded.

Nonetheless, its contribution to bringing the pandemic under control has to be applauded.

An evaluation published by the Economist magazine in July 2022 estimated that the Astrazeneca and Pfizer vaccines had each prevented around six million premature deaths.

Outside of the UK, Europe and North America, the Astrazeneca vaccine has been used more than any other, making a massive contribution to saving lives in less affluent parts of the world. This is partly because Astrazeneca opted to forego potentially massive profits and distribute it at cost price – £3.60 – and also because it was easier to manufacture and store compared to the MRNA vaccines.

Dr Michael Head, an expert in global health at the University of Southampton, noted that “there would have been far more deaths, hospitalisations, illness and transmission, if we hadn’t had the Astrazeneca vaccine”, especially in nations such as India.

However, it also has to be acknowledged that the vaccine has been linked to catastrophic and sometimes deadly side-effects in a very small number of recipients, and we still do not know exactly what happened or why.

Cases of TTS – sometimes called vaccine-induced thrombocytopenia and thrombosis (VITT) – began to emerge in the spring of 2021 as the rollout accelerated into younger age groups.

This was misleadingly interpreted by some as a sign that the vaccine had been rushed out, bypassing the usual clinical trial safeguards.

In reality, no clinical trial for any medicine is ever going to recruit tens or hundreds of thousands of people: it would take far too long.

Tested on thousands of participants over 10 months, the AZ vaccine was safe and effective and, in the context of an unfolding pandemic emergency, there was the funding and impetus needed to accelerate the process.

That does not mean that corners were cut, but when millions of doses are given in a short period of time it makes it possible to detect in the real world an abnormality that trials would never find.

The precise incidence rate for TTS is still contested, but NHS England previously put the figure at around one in 50,000 among under-50s given the AZ vaccine, and one in 100,000 for the over50 age group.

For older adults, the risk of serious complications if they contracted Covid while unvaccinated still far outweighed the risk of developing blood clots following vaccination, but this narrowed for younger generations.

In April 2021, modelling suggested that for adults aged 20-29 the chances of developing a vaccine-induced blood clot was fractionally higher than the probability of being admitted to intensive care as a result of Covid (1.1 versus 0.8 per 100,000), although this was based on an assumption that Covid circulation was low.

At “medium” levels, the risk from Covid was higher – even for twenty-somethings.

As stocks of the Pfizer and Moderna MRNA vaccines increased it made sense to prioritise these as a precaution to the under-30s and, latterly, the under-40s.

Three years on, however, UK taxpayers could face a hefty damages bill for those harmed by the AZ vaccine.

When the rollout began, the UK Government indemnified Astrazeneca, meaning that it would accept liability for any rarer side-effects not picked up during clinical trials.

A class action on consumer protection grounds is being pursued through the High Court by 51 Brits allegedly maimed or bereaved by TTS – which can result in strokes, brain haemorrhages, or disability if people have to undergo amputation.

They are seeking compensation up to £100 million.

Legal papers lodged with the court in February, but only disclosed at the end of April, show Astrazeneca acknowledging that its vaccine “can, in very rare cases, cause TTS”.

However, it also stresses that the “causal mechanism is not known” and that TTS “can also occur in the absence of the AZ vaccine (or any vaccine)”.

It is notable that these rare blood clots were also seen in the Johnson & Johnson (Janssen) single dose Covid vaccine – also discontinued, and also formulated using a chimp adenovirus as the vector.

Yet, prior to the pandemic, the same design was used for many years, apparently without incident, in Ebola vaccines.

Clare Bryant, an immunologist at Cambridge University, suspects that the sheer scale of the Covid vaccine rollout brought a hidden problem to light.

She recently told the Naked Scientist podcast: “When you’ve got a side-effect that’s occurring in one in 10,00 people then you will pick it up if you’re giving millions, billions, of doses.

“We don’t know about things like the Ebola vaccine – it’s possible [the same complication was occurring] but we will have to wait and see.”

Crucially, she added, if scientists can decipher the causal mechanism then they might be able to fix it, probably by tweaking the “adenovirus backbone”.

The technology remains a fantastic tool for creating cheap vaccines against various diseases.

In the long-run, the issues thrown up by the Covid vaccine could pave the way to even safer, life-saving jags in future.