Another covid-19 vaccine joins the party

Source

ON NOVEMBER 23RD, for the third Monday in a row, the results of an anti-covid vaccine were announced. This time the protagonists were AstraZeneca, a British-Swedish pharmaceutical company, and Oxford University. They reported their vaccine to be 70% effective. But doubts have since arisen about the conduct of the trials which arrived at this figure.

The consortium’s researchers estimated their vaccine’s efficacy from interim data collected by trials in Britain and Brazil. These involve more than 23,000 volunteers, half of whom have received the vaccine and the other half a placebo of one sort or another. Like the previous offerings (one from a partnership between Pfizer, a big American pharma company, and BioNTech, a small German one; the second from another American firm, Moderna), the AstraZeneca-Oxford inoculation is administered in two jabs. Of those given it, none has been admitted to hospital with covid-19, nor suffered a severe case of it. The researchers from AstraZeneca and Oxford also say that their vaccine may reduce passage of the virus between people—a property not yet established for either of the other two. An ideal vaccine needs to break the chain of transmission, as well as stopping recipients from falling ill, so this claim is important.

Half measures?

The consortium’s claim of 70% efficacy is, however, complicated by concerns about a slip-up during the trials which meant some participants were given only a half-dose of the vaccine to start with, followed by a full one. Intriguingly, the efficacy of this approach seemed to be about 90%. But if that is confirmed as correct, it follows that the efficacy of the intended protocol is actually only 62%. Further complications are that the half-dose group was a small fraction of the total, making statistical analysis less robust, and that group members were under 55, rather than fully representative of the population.

Why a lower initial dose might yield a stronger response is puzzling. The answer may lie in how the AstraZeneca-Oxford vaccine delivers genetic material from the coronavirus into the recipient’s body, in order to stimulate that person’s immune system. It uses what is known as a viral vector to carry this material, a substance called RNA that is a cousin of DNA. The other two vaccines deliver RNA as a “naked” molecule, wrapped up in a fatty bubble.

Before the trials began, some researchers had worried that going down the viral-vector route might cause people to develop immunity to the vector as well as to the coronavirus proteins which the RNA payload would encourage that person’s cells to make. The findings from the accidental subgroup hint that anti-vector immunity may, indeed, be happening, causing a large first dose to prime the body to develop antibodies to the vector. These would then attack the second-dose vectors before they could do their job. A smaller first dose might diminish this priming effect—explaining the better efficacy of unequal doses. The researchers expect to gather more information about the nature of the immune response in the weeks ahead.

As with data on the other two vaccines, much of the information provided so far is frustratingly preliminary. However, the Oxford group say they hope soon to submit a paper, presumably containing fuller information, to a journal. It is not clear when those developing the other two vaccines will do the same, but data from their trials will be made available prior to meetings with the American regulator in December.

Haste versus speed

The headline figure of 70% efficacy contrasts superficially with announced values of 95% for the other two vaccines. But, tempting as it is to compare these figures, that is actually hard to do. The most important reason for this is that developers count covid-19 cases in different ways. In particular, the AstraZeneca-Oxford trials checked participants for asymptomatic infection, rather than relying on self-reported symptoms to establish who was infected. The number of cases after vaccination may therefore seem higher than for the Pfizer-BioNTech and Moderna jabs, which relied on self-reporting by patients with a follow-up confirmatory test.

One bonus of the AstraZeneca-Oxford offering is that, if approved, it could be rolled out quickly. Pascal Soriot, AstraZeneca’s boss, says his firm has partnerships with suppliers in India, Latin America, Russia and Thailand. The Serum Institute in India agreed to manufacture the vaccine in bulk as long ago as April. “We are going to supply low- and middle-income countries around the world from different sources,” Mr Soriot says. “We are aiming at doing this more or less at the same time, so everybody gets access in an equitable manner as quickly as possible.” Altogether, AstraZeneca says the capacity exists to make 3bn doses of its vaccine over the course of next year. That compares with 1.3bn of the Pfizer-BioNTech vaccine, while Moderna hopes for between 500m and 1bn.

The AstraZeneca-Oxford vaccine is also cheap, and can be kept for at least six months in a normal refrigerator, meaning it can be stored in any surgery or pharmacy around the world. Moderna’s vaccine, by contrast, can be kept in an ordinary fridge for just a month. The Pfizer-BioNTech offering is even more sensitive. For most of the time it needs ultra-cold storage at -70°C. It can sit in a standard fridge for only a few days. Richard Hatchett, the head of CEPI, a foundation that pays for research into vaccines against novel pathogens, says he thinks the AstraZeneca-Oxford vaccine has the potential to alter the course of the pandemic, and could be delivered anywhere, including poor countries.

Although AstraZeneca says its vaccine was well tolerated by those who received it, questions remain about an unknown adverse event which caused trials to be halted temporarily earlier this year. These, and other matters, must now be considered by regulators, as they assess applications for emergency authorisation that the makers of all three vaccines will submit. AstraZeneca says it will also seek an emergency listing from the World Health Organisation. That would permit its jabs to be used in places which do not have regulatory authorities capable of assessing vaccines.

If time were not of the essence, it would make sense to wait for longer-term data on all the new vaccines. But in the face of a pandemic, that is not sensible. Regulations to allow for emergency use are designed for just such situations. Regulators will, however, have to keep tight control of these new vaccines to start with. At the outset their use will probably be restricted to those who need them most—doctors, nurses and other health-care workers, and also the elderly. Regulators will also insist on close monitoring for side-effects. But, as data accumulate over the first months of next year, those chains are likely to be loosened. The past three weeks, then, have transformed the prospects for 2021. The world now knows covid vaccines are possible. Let the hard work begin.