Almost a month after Russia announced approval for 'Sputnik V' COVID-19 vaccine, the first peer-reviewed studies published in the medical journal The Lancet noted that the vaccine evoked antibody response in all participants with no serious adverse events in small human trials.
The Russian coronavirus vaccine, from the day it was first announced to huge fanfare, has split opinion. While experts have questioned the rapidness with which the vaccine tests were done, and the lack of transparency in the results, Russian president Vladimir Putin had assured that it had passed the required checks, adding that one of his daughters was administered the vaccine.
In the current global vaccine race, Moscow sees its development of the COVID-19 vaccine as a Sputnik-like propaganda victory, recalling the Soviet Union's launch of the world's first satellite in Cold War 1957. The closest Western competitors to Sputnik V are the Moderna and Oxford-AstraZeneca vaccines, both of which are currently in Phase III large-scale testing. Delivering a vaccine first is a matter of national prestige for the Kremlin as it tries to assert the image of Russia as a global power capable of competing with the US and China. That political angle, experts claim, does not bode well for the medical community.
A lot of ethical issues have also been raised vis-a-vis the vaccine. In April, President Vladimir Putin ordered state officials to shorten the time of clinical trials for a variety of drugs, including potential coronavirus vaccines. According to Russia's Association of Clinical Trials Organisations, the order set “an unattainable bar” for scientists who, as a result, "joined in on the mad race, hoping to please those at power". The association first raised concern in late May, when professor Alexander Gintsburg, head of the Gamaleya institute developing the vaccine, said he and other researchers tried the vaccine on themselves. The move was a "crude violation of the very foundations of clinical research, Russian law and universally accepted international regulations", the group said in an open letter to the government, urging scientists and health officials to adhere to clinical research standards.
So, what does the new Lancet study tell us? Is there more to it than meets the eye?
How does the vaccine work?
The two-part vaccine, with a primary shot and a booster dose, includes recombinant human adenovirus type 26 (rAd26-S) and recombinant human adenovirus type 5 (rAd5-S), which have been modified to express the signature SARS-CoV-2 spike protein.
Simply put, when the adenovirus vaccine enters cells, they deliver the SARS-CoV-2 spike protein genetic code, which causes cells to produce the spike protein. This helps teach the immune system to recognise and attack the SARS-CoV-2 virus. The adenoviruses, which usually cause the common cold, are also weakened so that they cannot replicate in human cells and cannot cause disease.
These vaccines aim to stimulate both arms of the immune system—antibody and T-cell responses—so they attack the virus when it is circulating in the body, and also attack cells infected by SARS-CoV-2.
What do the tests tell us?
According to The Lancet, results from early-phase non-randomised vaccine trials in a total of 76 people showed that two formulations of the vaccine have a good safety profile detected over 42 days, and induce antibody responses in all participants within 21 days. Secondary outcomes from the trial suggest the vaccine, approved last month by Russia, also produces a T-cell response within 28 days, the researchers said.
The trials took place in two hospitals in Russia, and were open-label and non-randomised, meaning that participants knew that they were receiving the vaccine and were not assigned by chance to different treatment groups. The trials involved healthy adults aged 18-60 years, who self-isolated as soon as they were registered, and remained in hospital for the first 28 days of the trial from when they were first vaccinated.
In the Phase I of each trial, participants received one component of the two-part vaccine—four groups of nine participants were given the frozen or freeze-dried rAd26-S or rAd5-S component. In the Phase II, which began no earlier than five days after the phase I trial began, participants received the full two-part vaccine. There were 20 participants each in the frozen and freeze-dried vaccine groups, the Lancet study noted.
To compare post-vaccination immunity with natural immunity formed by infection with SARS-CoV-2, the authors obtained convalescent plasma from 4,817 people who had recovered from mild or moderate COVID-19, they said.
Both vaccine formulations were safe over the 42-day study period and well tolerated, according to the study. The most common adverse events were pain at the injection site, hyperthermia, headache, asthenia (weakness or lack of energy), and muscle and joint pain. The authors note that these adverse effects are also seen with other vaccines, particularly those based on recombinant viral vectors.
Understanding the studies in context: Will the vaccine work?
The immunogenicity produced in the trials bodes well, but the issue remains that the tests are small-scale.
Vaccine testing is a four-stage process—pre-clinical testing on animals; Phase I clinical testing on a small group of people to determine its safety and to learn more about the immune response it provokes; Phase II trials, or expanded safety trials, where dosage and frequency will be tested across wider cross-sections of the population; Phase III large-scale tests where the vaccine is administered to thousands of people to confirm its efficacy. Phase I and phase II are the early trials, which will then be followed by a rigorous, intensive Phase III clinical testing, where the longevity of the vaccine response (whether the vaccine will last for long periods of time) will be analysed.
The Sputnik V vaccine has not completed the Phase III large-scale trials, which is the defining hurdle in any vaccine development.
Also, as the authors themselves have noted, there are massive limitations to the study, including that it had a short follow-up (42 days), it was a small study with less than 100 participants, some parts of the Phase I trials included only male volunteers, and there was no placebo or control vaccine. In addition, their study included fairly young volunteers (in their 20s and 30s, on average), so nothing can be understood as to the immunogenicity among older adults. More research is needed to evaluate the vaccine in different populations, including older age groups, individuals with underlying medical conditions, and people in at-risk groups.
In an accompanying commentary to The Lancet study, Dr. Naor Bar-Zeev of the Johns Hopkins Bloomberg School of Public Health and colleagues wrote that the studies were encouraging but small. They said that the immune reaction elicited by the vaccine bodes well, but that efficacy for any COVID-19 vaccine has not yet been shown. Bar-Zeev and colleagues said that proving the safety of any coronavirus vaccine would be critical. "Since vaccines are given to healthy people and during the COVID-19 pandemic, potentially to everyone after approval following [advanced] trials, safety is paramount," the scientists wrote.
Dr Ohid Yaqub, senior lecturer at the Science Policy Research Unit at the University of Sussex, said the limited study size was not enough for regulatory approval, which the vaccine received last month. "The design and size of [an early] study is not anywhere near sufficient for widely recognized standards of approval. The study was not randomised, and it was not large enough to detect rarer safety issues," Yaqub said.
What do the Russians plan to do next?
Explaining the next steps of their research, Professor Gintsburg from Gamaleya National Research Centre said the Phase III clinical trial of the vaccine has been approved on August 26, 2020.
"It is planned to include 40,000 volunteers from different age and risk groups, and will be undertaken with constant monitoring of volunteers through an online application," Gintsburg told media.
In April, President Vladimir Putin ordered state officials to shorten the time of clinical trials for a variety of drugs, including potential coronavirus vaccines. According to Russia's Association of Clinical Trials Organizations, the order set “an unattainable bar” for scientists who, as a result, "joined in on the mad race, hoping to please those at power.”
The association first raised concern in late May, when professor Alexander Gintsburg, head of the Gamaleya institute developing the vaccine, said he and other researchers tried the vaccine on themselves. The move was a “crude violation of the very foundations of clinical research, Russian law and universally accepted international regulations", the group said in an open letter to the government, urging scientists and health officials to adhere to clinical research standards.
In April, President Vladimir Putin ordered state officials to shorten the time of clinical trials for a variety of drugs, including potential coronavirus vaccines. According to Russia's Association of Clinical Trials Organizations, the order set “an unattainable bar” for scientists who, as a result, "joined in on the mad race, hoping to please those at power.”
The association first raised concern in late May, when professor Alexander Gintsburg, head of the Gamaleya institute developing the vaccine, said he and other researchers tried the vaccine on themselves. The move was a “crude violation of the very foundations of clinical research, Russian law and universally accepted international regulations", the group said in an open letter to the government, urging scientists and health officials to adhere to clinical research standards.
In April, President Vladimir Putin ordered state officials to shorten the time of clinical trials for a variety of drugs, including potential coronavirus vaccines. According to Russia's Association of Clinical Trials Organizations, the order set “an unattainable bar” for scientists who, as a result, "joined in on the mad race, hoping to please those at power.”
The association first raised concern in late May, when professor Alexander Gintsburg, head of the Gamaleya institute developing the vaccine, said he and other researchers tried the vaccine on themselves. The move was a “crude violation of the very foundations of clinical research, Russian law and universally accepted international regulations", the group said in an open letter to the government, urging scientists and health officials to adhere to clinical research standards.
