Russia’s coronavirus vaccine shows no serious adverse effects and produces antibody response, finds study
In August, Russia became the first country in the world to approve a vaccine for Covid-19, which has been dubbed “Sputnik V.” Russian President Vladimir Putin made the announcement on August 11. Scientists criticized the move as no scientific data had been published about its safety or efficacy and the crucial phase three clinical trials had not yet been completed. Now, early-phase results from Russia’s vaccine trials reveal that Sputnik-V induced antibody responses in all participants within 21 days. The two 42-day trials -- including 38 healthy adults each -- did not find any serious adverse effects among participants, said a study published in the peer-reviewed medical journal, The Lancet.
“Two formulations of a two-part vaccine have a good safety profile with no serious adverse events detected over 42 days, and induce antibody responses in all participants within 21 days. Large, long-term trials including a placebo comparison and further monitoring are needed to establish the long-term safety and effectiveness of the vaccine for preventing Covid-19 infection,” write authors.
The new paper reports the findings from two small phase 1/2 trials lasting 42 days -- one studying a frozen formulation of the vaccine, and another involving a lyophilized or freeze-dried formulation of the vaccine. The frozen formulation is envisaged for large-scale use using existing global supply chains for vaccines, while the freeze-dried formulation was developed for hard-to-reach regions as it is more stable and can be stored at 2-8 degrees centigrade.
The results
The trials took place in two hospitals in Russia. They were open-label and non-randomized, 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 for the trial and remained in the hospital for the first 28 days of the trial, that is, from when they were first vaccinated. The trial was designed to study the number of adverse events of the vaccines (safety), and the antibody response elicited by the vaccines (immunogenicity).
“The two-part vaccine included two adenovirus vectors - recombinant human adenovirus type 26 (rAd26-S) and recombinant human adenovirus type 5 (rAd5-S). The adenoviruses were weakened so that they cannot replicate in human cells and cannot cause disease (adenovirus usually causes the common cold). In the phase 1 part of each trial, the individual components of the two-part vaccine were tested for safety. The phase 2 study then tested whether the vaccine elicited an immune response by giving the full two-part vaccine,” say researchers.
The results show that both vaccine formulations were safe over the 42-day study period and well-tolerated. The most common adverse events were pain at the injection site (44 out of 76 participants or 58%), hyperthermia or high temperature (38 out of 76, 50%), headache (32 out of 76, 42%), asthenia or weakness or lack of energy (21 out of 76, 28%), and muscle and joint pain (18 out of 76, 24%). Most adverse events were mild, and no serious adverse events were detected within 42 days of vaccination. The authors explain that these adverse effects are characteristic of those seen with other vaccines, particularly those based on recombinant viral vectors. All participants in phase 2 trials produced antibodies.
The authors note some limitations to their study, including that it had a short follow-up of 42 days, it was a small study, some parts of the phase 1 trials included only male volunteers, and there was no placebo or control vaccine. Besides, they say that despite planning to recruit healthy volunteers aged 18-60 years, in general, their study included fairly young volunteers, in their 20s and 30s, on average. Accordingly, the team says that 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.
Explaining the next steps, Professor Alexander Gintsburg, N F Gamaleya National Research Centre for Epidemiology and Microbiology, Russia, says: “The phase 3 clinical trial of our vaccine was 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.”
What are experts saying?
Writing in a linked comment, lead author Dr Naor Bar-Zeev, International Vaccine Access Center, Johns Hopkins Bloomberg School of Public Health, US, who was not involved in the study, says that the results are “encouraging but small.”
“The immunogenicity bodes well, although nothing can be inferred on immunogenicity in older age groups, and clinical efficacy for any Covid-19 vaccine has not yet been shown. Showing safety will be crucial with Covid-19 vaccines, not only for vaccine acceptance but also for trust in vaccination broadly. Safety outcomes up to now are reassuring, but studies to date are too small to address less common or rare serious adverse events. Unlike clinical trials of therapeutics, in which safety is balanced against benefit in patients, vaccine trials have to balance safety against infection risk, not against disease outcome. Since vaccines are given to healthy people and, during the Covid-19 pandemic, potentially to everyone after approval following phase 3 trials, safety is paramount,” explains Dr Bar-Zeev.
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Eleanor Riley, professor of Immunology and Infectious Disease at the University of Edinburgh, who was not involved in the research, says that scaling up vaccine production at this stage is not unreasonable. “We are doing the same here with the Oxford and Imperial College vaccines and you need to begin to scale up to have enough vaccines to conduct a large phase 3 trial. The key question is whether the next step for this vaccine is indeed (as we would expect) a randomized, blinded, placebo-controlled phase III trial or whether the vaccine developers will come under political pressure to release doses of vaccine for administration to the general public. The approval granted for the vaccine – apparently under a law introduced after the onset of the pandemic – allows for both,” writes Riley.
According to Dr. Ohid Yaqub, senior Lecturer at the Science Policy Research Unit, University of Sussex, normally, such a study would be the basis for debating whether to proceed into larger trials and the costs that entail. “In that context, the study results are encouraging in terms of safety and possible efficacy. However, in the context of regulatory approval, the design and size of a phase 1/2 study are not anywhere near sufficient for widely recognized standards of approval. It was not large enough to detect rarer safety issues. Further work, and its full and open disclosure, is to be encouraged,” suggests Dr Yaqub.
Dr Michael Head, senior research fellow in global health at the University of Southampton, says that this appears to be a promising vaccine candidate. “Concerns do remain around some of the previously-made ambiguous comments that this vaccine is about to be formally approved and licensed. At this stage, we do not know if the vaccine actually works – that is what the phase 3 trials will tell us. Public confidence in any licensed vaccine is vital, and suggestions from both Russia and the USA that a vaccine may be fast-tracked without the proper research having taken place are problematic. We must be open and transparent about the effectiveness and safety profiles of all vaccine candidates. Ultimately, we must not pour additional fuel on the anti-vaccine lobby fires,” emphasizes Dr Head.