News reports suggest Russia has approved a COVID-19 vaccine after two months of tests in humans.
Our colleagues at the UK SMC gathered expert reaction to the claims.
Prof Jonathan Ball, Professor of Molecular Virology, University of Nottingham, said:
“Vaccine candidates go through a series of trials to ensure that they are safe and also that they work. A major challenge for any COVID vaccine will be the need to protect the most vulnerable groups – for example the elderly with other health conditions such as diabetes – from disease. If that isn’t achievable then any useful vaccine will need to reduce the chances of other people infecting vulnerable people, either by providing sterilising immunity – meaning that less vulnerable people don’t get infected, or failing that ensuring that when they do become infected that they are unable to transmit the virus to others. The only sensible way to get this information is through very large well-designed phase 3 trials”.
“Whilst details about the Russian vaccine are scant, it does appear to have gone through the early trial phases, so it’s safety profile should be reasonably well known, but whether it will work has not been established and therefore it doesn’t strike me as being very sensible to roll this out routinely.
Prof Ian Jones, Professor of Virology, University of Reading, said:
“I think there is enough general background data on recombinant Adenovirus based vaccines to assume the vaccine itself will be safe at the usual doses. The bigger risk, however, is that the immunity generated is not sufficient to give protection, leading to continued virus spread even among immunised individuals. And although only a possibility, less than complete protection could provide a selection pressure that drives the virus to evade what antibody there is, creating strains that then evade all vaccine responses. In that sense, a poor vaccine is worse than no vaccine. Careful virus tracking will therefore need to accompany any early release.”
Prof Peter Openshaw, Professor of Experimental Medicine at the National Heart & Lung Institute, Imperial College London, said:
“It’s important to emphasise that this vaccine has not been approved or even fully tested. The Russian health authorities are discussing the process for possible WHO pre-qualification as an approved vaccine.
“There are currently 19 vaccines that have been tested for the ability to generate antibody (Phase I), another 11 that have passed this stage and gone on to expended testing (Phase II), eight at Phase III and one vaccine approved for limited use.
“So far, it is reported that the Russian vaccine has undergone less than two months of human testing in a total of 38 people. It appears to be at Phase I or II. According the news sources, there is a Phase III trial of 1,600 people planned. That’s not actually very large for a vaccine trial and would assume a high rate of infection in the volunteers. How would that be achieved, given that rates that are reported from Russia are currently low?
“It is a human adenovirus-based vaccine, similar in some ways to the chimp adenovirus vaccine being developed by Sarah Gilbert in Oxford. It is given as an intramuscular injection in studies conducted in June and July, and was apparently found to induce antibody responses with an acceptable level of adverse effects. Common side effects would include fever, malaise and headache with this type of live vectored vaccine; it seems that President Putin’s own daughter did indeed have such a reaction when the vaccine was given to her.
“This raises a concern that the experimental vaccine is being given to the Russian elite before it has undergone full testing in a formal clinical trial. Treatments (and possibly vaccines) might sometimes be given on ‘compassionate’ grounds, but only in very limited circumstances. The apparent use of this vaccine in people who are not at very high risk of exposure to SARS-CoV-2 or death from COVID, raises significant concerns.”
Mike Turner, Head of Major Science Investments at Wellcome, said:
“Safety is the most important consideration when developing any vaccine. COVID-19 is the greatest vaccine development challenge in history, but speed should not compromise safety.
“Without the data on this vaccine being released, it is impossible to assess its efficacy or safety – even in early testing – but this data must be shared openly and transparently to maintain public trust.
“Before any vaccines are rolled out at a population level, they must be tested in robust clinical trials (Phase 1-3) to ensure they are as safe as possible. Continuing to monitor the safety and efficacy of COVID-19 vaccines will be critical to rapidly picking up on any potential rare side effects, as well as the effectiveness of the vaccines on a large scale.
“To bring this pandemic to an end we need safe and effective vaccines, treatments and diagnostics for COVID-19 available to everyone, everywhere.”
Dr Ohid Yaqub, Senior Lecturer in the Science Policy Research Unit, University of Sussex, said:
“This approval seems to have been made before phase 3 trials have been completed. Phase 3 trials are longer and larger in order to detect rare side effects, and get a better sense of efficacy. Moreover, there is little by way of published data and evidence about this vaccine.
“In terms of safety, skipping phase 3 means trust in this vaccine – and vaccines generally – could be undermined, and it could also give people a false sense of security, if it turns out the vaccine is not actually effective. Another important implication is that, if there is widespread diffusion of this vaccine, it may interfere with the testing of future vaccines that are potentially better.
“I would hope that other countries are not drawn into such pork-barrel vaccine nationalism. It’s strangely reminiscent of Lysenkoism. The less that vaccine development looks like this, the better. Decision making should published, open to scrutiny, and free from flag-waving. We should resist allowing vaccine development to be used as a measure of national scientific prowess.”
Prof Francois Balloux, Professor of Computational Systems Biology at University College London and Director of the UCL Genetics Institute, said:
“This is a reckless and foolish decision. Mass vaccination with an improperly tested vaccine is unethical. Any problem with the Russian vaccination campaign would be disastrous both through its negative effects on health, but also because it would further set back the acceptance of vaccines in the population.”
Prof Eleanor Riley, Professor of Immunology and Infectious Disease at the University of Edinburgh, said:
“There are precedents for rapid approval of experimental vaccines during epidemics. Qualified approval (for emergency use) is granted to enable deployment in areas of exceptional need in an effort both to gather data on vaccine efficacy and to attempt to stop the spread of a deadly disease. Roll out of experimental Ebola vaccines during the recent West African outbreak is a case in point. Importantly, the roll out is conducted in a discrete, high risk setting with sufficient resource to monitor adverse events and efficacy, and with the oversight of an independent data and safety monitoring board. For Ebola this was justified by the very high transmission and case fatality rates and the very high risks posed to health care and sanitation workers involved in controlling the outbreak. In essence, the risk of receiving an experimental vaccine was deemed to be lower than the risk of contracting and dying from Ebolavirus.
“Arguably, these justifications do not (or no longer) pertain in the case of the COVID-19 pandemic. The individual risk of dying from COVID-19 is low, and in many countries it is falling, and we have effective public health measures to sustain this in the short to medium term. At this stage of the pandemic, with transmission low or falling in many countries, COVID-19 vaccine trials need to be large in order to gather enough data on infections to determine whether they work. But there is a big difference between a large vaccine trial (with careful and frequent follow up of all vaccinated individuals) and deployment of a vaccine to the general public. The current messaging from Russia is very unclear as to which of these two deployments – a large phase 3 clinical trial or mass vaccination of the general public – is being proposed.”
Dr Ayfer Ali, a specialist in drug research at Warwick Business School, said:
“One problem with fast approvals is that we will likely miss potential adverse effects which are rare but serious.
“Another issue is missing potential antibody-dependent enhancement (ADE) which is a phenomenon where a vaccine is not protective enough to prevent the disease but instead allows the virus to enter the body more easily and worsen the disease the vaccine is supposed to protect against.
“This has been observed in animal models of non-Covid-19 coronavirus vaccines before. When such a phenomenon or is observed in small studies testing can be stopped and damage limited. When this happens at the population level, it can have devastating effects. That is one reason proper testing is paramount. Russia is essentially conducting a large population level experiment.”
Prof Danny Altmann, Professor of Immunology at Imperial College London, said:
“There are many vaccines in development around the world and we all share an interest in this being a truly open, global effort to use the very best vaccines – in terms of protection, safety and durability.
“While information on the vast majority of the vaccines and trial protocols in the world have been made available, there seems to be rather little detail thus far on the Russian candidates, except for a protocol on Clintrials.gov, which seemed to suggest an adenovirus vector.
“The bar is necessarily set very high for criteria that must be satisfied for approval after Phase 3 clinical trials. The collateral damage from release of any vaccine that was less than safe and effective would exacerbate our current problems insurmountably. I hope these criteria have been followed. We are all in this together.”
Prof Keith Neal, Emeritus Professor of the Epidemiology of Infectious Diseases, University of Nottingham, said:
“There are a number of steps that need to be taken before a vaccine is used at a population level.
“These include Does it induce an immune response? and How safe is it? These are relatively easy to do as they only require small numbers.
“The next stage is Does it prevent the disease? This is always a problem if the disease is rare and for COVID-19 in Western Europe this has happened. As this happens large trials are required as so few people are acquiring infection. Hence, additional trials of vaccines may have, or may be soon, started in countries such as the USA, Brazil and South Africa where infrastructures to support vaccine trials already exist.
“Using the figures from www.worldometer.com an infection rate of 5000 per day equates to 1 per 1000 a month in Russia and this may be significantly under-reported. This will be higher in Moscow and probably health care workers. If 25,000 people were recruited in each arm then we would expect 25 cases in one month in the control group. Any figure less than 15 COVID-19 cases in the vaccine arm would be significant. Given the size of the Russian population, recruiting 50,000 people is well deliverable. Only 12,500 for two months gives the same results.
“It is not possible to know if the Russian vaccine has been shown to be effective without submission of scientific papers for analysis and then there may be problems on data quality.
“If the disease becomes seriously out of control there is a case for carrying out a phase 3 drug trial particularly including those at highest risk at the population level.”
Dr Michael Head, Senior Research Fellow in Global Health, University of Southampton, said:
“It is unclear precisely what is actually happening with the Russian vaccine. It is vital that any vaccine roll-out has the confidence of the general public, and that there is good communication of the level of effectiveness and any likely side effects. At this point in time, there is no data on the Russian-led vaccine for the global health community to scrutinise. There have been lessons learned from previous vaccine roll-outs, that were usurped by anti-vaccination activists and population health has greatly suffered. Examples include the HPV vaccine in Denmark or Japan, where uptake plunged after anti-vaccine campaigns and irresponsible comments from some scientists. Health promotion and clear explanations to the general public are the bare minimum in terms of communications here.”
Professor Duncan Matthews, Professor of IP Law at Queen Mary University of London, said:
“News of a potential Covid-19 vaccine is to be welcomed but safety must be the priority. The U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have fast-track approval procedures for emergency humanitarian use and we need to see evidence that Russia is adopting an equally prudent approach.”