Russia approves first Covid-19 vaccine without completing tests, here’s all you need to know about ‘Sputnik V’
The final phase of clinical tests, known as Phase 3, tests the vaccine in thousands of people and compares it to a placebo to determine whether it is safe and effective in a general population
Russia has become the first country in the world to approve a vaccine for the coronavirus. On August 11, Russian President Vladimir Putin made the announcement, stating that one of his daughters has already taken a dose. The vaccine, which has been dubbed “Sputnik V” in homage to the world’s first satellite launched by the Soviet Union, has, however, not yet completed its final clinical trial. What do we know about this unverified coronavirus vaccine so far?
Who is developing the vaccine?
The Russian vaccine, developed in cooperation between the Gamaleya Research Institute of Epidemiology and Microbiology, has completed Phase 1 and 2 clinical trials with several small groups of volunteers. “Russia’s Health Ministry has registered the vaccine against the coronavirus infection developed by the Gamaleya Research Center as a solution for injections. It will appear in circulation starting on January 1, 2021, the website of the State Register of Pharmaceuticals reported on Tuesday,” states TASS Russian news agency. The registration certificate shows that it is being manufactured by Binnopharm in Zelenograd and mentions that the “term of introduction into civil circulation” will be January 1 next year.
Putin endorsed the vaccine, saying, “I know that it works quite effectively, forms strong immunity, and I repeat, it has passed all the necessary checks.” But not much is known about the vaccine, and there are widespread concerns and unanswered questions over its safety and effectiveness.
Full-scale production of the vaccine is expected to begin in September. The Russian business conglomerate Sistema has said it expects to put the vaccine, developed by Moscow’s Gamaleya Institute, into mass production by the end of the year. However, vaccination of doctors could start as early as this month, said Deputy Prime Minister Tatyana Golikova. “We expect tens of thousands of volunteers to be vaccinated within the next months,” said Kirill Dmitriev, chief executive of the Russian Direct Investment Fund, according to AP.
How many people have been tested?
Few details of the Gamaleya research have been made public or have undergone peer review. Reports suggest that Sputnik V’s Phase 1 and 2 trials involved 76 participants in total. According to the US National Library of Medicine, all 38 participants who received either one or two doses in one of those trials produced antibodies. Results from those trials or other preclinical studies have not been published yet.
The vaccine consists of two shots or doses to deliver different harmless cold viruses or adenoviruses. These viruses have been engineered to make the coronavirus spike protein that helps SARS-CoV-2 (the virus that causes Covid-19) latch on to cells and infect them.
“According to the ClinicalTrials.gov listings, the vaccine, which is given in two doses, is made of two adenoviruses that express the coronavirus spike protein. The first dose is an Ad26 virus — the same strain being used in an experimental vaccine being developed by pharmaceutical company Johnson & Johnson and its subsidiary Janssen. The second ‘booster’ dose is made of an Ad5 virus, like the one in an experimental jab being developed by CanSino Biologics in China,” explains Nature.
Why is Phase 3 trial critical?
Vaccines usually undergo three phases of clinical tests. The first two phases test the vaccine in small numbers of people for safety and may collect data on whether people make antibodies or have other responses to the vaccine.
The final phase, known as Phase 3, tests the vaccine in thousands of people and compares it to a placebo to determine whether it is safe and effective in a general population. The last phase is critical as it determines whether it can prevent or lower the infection. Since the tests are conducted in a much larger group, a Phase 3 trial can also identify more subtle adverse effects of a vaccine that earlier trials might not have been able to. In the case of Sputnik V, the Phase 3 clinical trial is yet to be started. “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,” emphasized Mike Turner, head of major science investments at Wellcome.
“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," explained Keith Neal, emeritus professor of the epidemiology of infectious diseases, University of Nottingham.
According to TASS, the Russian Direct Investment Fund (RDIF) has agreed to hold the third stage of clinical trials of the Covid-19 vaccine abroad with the UAE, Saudi Arabia, and other states.
The Moscow-based Association of Clinical Research Organizations (AOKI), in an open letter to the Russian ministry of health, has asked the government to delay approval of the vaccine until after Phase 3 data is in and only if it successfully passes all stages of clinical development. “This is a new vaccine and has yet to complete testing in hundreds of people, let alone in the thousands of people in the Phase 3 study. It is worth emphasizing the high risks of drug registration before the end of Phase 3. It is during this phase that the main evidence of efficacy is obtained, as well as information is collected on the adverse reactions that the drug can cause in certain groups of patients: people with weakened immunity, people with concomitant diseases, etc,” says the letter.
Experts have criticized the move
Francois Balloux, professor of computational systems biology at University College London and Director of the UCL Genetics Institute, has called it 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,” said Balloux.
Florian Krammer, an immunologist at Mount Sinai's Icahn School of Medicine, tweeted: “Not sure what Russia is up to but I certainly would not take a vaccine that hasn't been tested in Phase III. Nobody knows if it is safe or if it works. They are putting HCWs (healthcare workers) and their population at risk.”
Not sure what Russia is up to but I certainly would not take a vaccine that hasn't been tested in Phase III. Nobody knows if its safe or if it works. They are putting HCWs and their population at risk.— Florian Krammer (@florian_krammer) August 11, 2020
According to Eleanor Riley, professor of immunology and infectious disease at the University of Edinburgh, 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,” argued Riley.
Peter Openshaw, Professor of Experimental Medicine at the National Heart & Lung Institute, Imperial College London, said it is important to emphasize that this vaccine has not been fully tested. “The Russian health authorities are discussing the process for possible WHO pre-qualification as an approved vaccine. 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 1 or 2. According to news sources, there is a Phase 3 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?” said Openshaw.
Anthony Fauci, director of the US National Institute of Allergy and Infectious Disease, said he hopes the Russians have “actually definitively proven” that the vaccine is safe and effective. “I seriously doubt that they've done that...We have half a dozen or more vaccines. So if we wanted to take the chance of hurting a lot of people or giving them something that doesn't work, we could start doing this, you know, next week if we wanted to. But that's not the way it works,” said Fauci, according to a National Geographic report.
When questioned regarding the Russian vaccine, US Health and Human Services Secretary Alex Azar emphasized that the point is not to be first with a vaccine. “The point is to have a vaccine that is safe and effective for the American people and the people of the world,” he said.