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Behind the spin: how effective are the vaccines?

Luigi Hay looks at the science behind the various vaccines, asks how effective each one is likely to be, and argues that vaccination should be used as one part of a strategy to end the pandemic, not as an isolated silver bullet.

The welcome beginning of the rollout of coronavirus vaccines has prompted speculation that the end of the Covid-19 pandemic is in sight. However, the recent rise in the number of cases, the second lockdown, and most of the country going into a higher level of restriction suggest that the pandemic is far from over.

The government allowing unsafe and non-essential workplaces to stay open, and pushing for full attendance at schools, means the virus will continue to spread. Johnson took the decision to lift many restrictions over Christmas – with a seasonal passing of the buck onto individuals for their ‘behaviour’ – but infections were already rising, and the Independent SAGE group predicted that the R figure (the average number of people each infected individual passes the virus on to) would be around 2 over Christmas. To control the spread of the disease, R must be under 1. At least many workplaces will have closed for a while over the Christmas-New Year period, and schools will be shut for a couple of weeks.

How does vaccine development work?

Stage 3 clinical trials involve a ‘double-blind placebo’ trial involving tens of thousands of people. Half the group is given the vaccine and half are given something that looks the same. Neither the participants nor the people administering the injections or recording the data know who is in the trial, only the statisticians at the end. There are 4 types of vaccine being researched:

• An inactivated or weakened form of virus: the ‘traditional’ form of vaccine. A Chinese pharmaceutical enterprise has stage 3 trials underway with a promise to make any resulting vaccine freely available for all.
• Protein-based: empty virus shells, with no genetic material, or specific protein ‘antigens’ (molecules that stimulate an immune response).
• Viral vector: in this case, capsules from other viruses are used to introduce part of the coronavirus genome, prompting our cells to produce a specific protein such as the spike protein that the virus uses to latch onto our cells. None of the viral replication genes are present. Both the Russian Sputnik V and the Oxford University/AstraZeneca (OAZ) vaccine are of this type.
• Nucleic acid: these also deliver the gene for producing the spike protein , but use a fatty droplet to allow them to enter the cell. Many scientists are quite excited about this technology, as it hasn’t been used on a mass scale before, and could make production swifter (and presumably also cheaper). Both the Pfizer/BioNTech and the Moderna vaccine are of this type.

The normal timeframe for developing a new vaccine is several years, but any process can be speeded up if sufficient funds are made available. Almost all of the vaccines under development have received research funding from governments, philanthropic organisations (such as the Gates Foundation), or international cooperative efforts such as the COVAX Facility.

Where these actors have made investment contingent on the vaccine being accessible, they have usually insisted that the vaccines should be affordable and accessible to all ‘for the duration of the pandemic’ – but companies could have broad latitude in deciding when the pandemic is declared to be over. If Covid-19 needs regular booster shots, then the pharmaceutical companies will make a financial killing for many years to come. Meanwhile, the Pfizer/BioNTech project has been an exception, with Pfizer funding the research but stating that they intended to make a profit from the vaccine from the start, projected at $13bn.

How effective are the vaccines?

The rewards of being the first company to develop a vaccine are immense, with a sharp rise in share prices likely leading to big dividend payouts and big bonuses for executives. The industry is notorious for bigging up their products with questionable claims. So what are we to make of the claims put forward by the vaccine manufacturers?

Pfizer were the first to announce their vaccine as passing trials with a 90% effectiveness for a 2-dose programme. However, the vaccine needs to be stored and transported at -70C and was not tested on older people, the most vulnerable to Covid. The World Health Organization recommends a minimum threshold of 50% effectiveness, so a vaccine that is 90% effective would easily satisfy this in theory, but what do these figures mean in practice?

The Pfizer Stage 3 trial featured 38,955 participants, with 94 cases of Covid-19 occurring post-vaccination. Of these, 85 cases (90%) occurred in the group of participants who had been given a placebo, and 9 occurred in the group that had been given the vaccine. This suggests that, if 100% of the UK population were to receive this vaccine, 10% would still be vulnerable (almost 7 million people). Covid-19 data suggests that 78% of the population need to achieve immunity in order to confer the fabled ’herd immunity’ upon the whole population, assuming it actually does prevent transmission as well as protecting the individual against the symptoms, and that new variants don’t change this figure. Given that 17% of UK adults say they would refuse to have the vaccine, with another 19% not sure, achieving this level of coverage is not a certainty. The government may be tempted, then, to consider compulsory vaccination – something which would set a dangerous precedent, and which would certainly invigorate the anti-vaxxers.

Moderna’s vaccine is easier to make and store (at -4C) and was also tested on an older cohort with a claimed effectiveness of 94.5%, while the Oxford/AstraZeneca vaccine is, bizarrely, more effective if the first dose is a half dose followed by a full dose, taking effectiveness to 90%. Manufacturing costs are £2 to £4 a dose compared to £15 for Pfizer’s and £26 for Moderna’s one. Over-70s were included and ‘responded well’ to the shot.

As yet, there is no firm proof that these vaccines will be able to stop the spread of coronavirus, for a number of reasons:

• The success rate for clinical trials is much higher than that of population-wide vaccination programmes, especially for those, like most of the vaccines in later stages of development, which require two doses.
• Statistically, there is often great variation in the uncertainty of results for vaccines.
• Most of the vaccines were given to predominantly young, and generally healthy, volunteers, who are less likely to develop severe symptoms from Covid-19.
• Even if a vaccine stops people developing symptoms, this may not mean that it will prevent transmission to others: there are a lot of asymptomatic cases of this coronavirus.
• The first 1800 doses given in the UK suggest that some people may show a serious allergic reaction, with 3 people responding in this way (though all quickly and fully recovered).
• The vaccine may not prevent an immunised person from transmitting the disease, I am unaware of any published research incorporating this factor. However, people with immunity to a virus normally host far fewer copies of it as well as being less likely to cough, reducing their infectiousness.
• No one knows how long immunity will last. Most publicly available research on this subject looks at antibody levels, finding there is only a ‘modest decline’ in these after 5 months. However, it is T cells which provide longer-lasting immunity to most diseases, and it is harder to find research on this subject; the detection of these is a lengthier and harder process.
• The vaccination programme is, optimistically, likely to take several months to roll out globally, most likely until the end of 2021. Hundreds of millions worldwide are unlikely to be immunised before then. There are currently no plans in the UK to vaccinate under 50s without health conditions, or to vaccinate under 16s, though this seems likely to change.
• The UK government is diverging from scientific recommendations in the rollout of the vaccine, delaying second jabs by up to 12 weeks and even suggesting that people may receive different vaccines on their first and second jabs in some cases.

For all these reasons while the development of several promising vaccines is a hugely hopeful development, we clearly cannot count on any of these being a silver bullet that ends the pandemic overnight. To save lives in the indefinite period of time until effective and long-lasting immunity can be achieved, we still desperately need a Zero Covid strategy (as part of which a vaccination programme can help to truly suppress and eliminate the virus). If we want the vaccine to be truly and globally accessible, we will also need to overcome the incentives of the pharmaceutical companies – which will be the subject of the second part of this article.