A study funded by the Ministry of Health of the Russian Federation has made public that their vaccine Sputnik V does not have any adverse effects and is effective in eliciting immune response. The findings of the first two phases of clinical trials were published in The Lancet on September 4, 2020.
The vaccine has to be taken in two doses — the initial and booster dose. Both doses use adenovirus (cold virus and generally considered safe) as the vector to ferry the novel coronavirus SARS-CoV-2 spike protein genetic code to the human body. These proteins teach the immune system of a person to recognise and attack the SARS-CoV-2 virus.
The two vectors are recombinant human adenovirus type 26 (rAd26-S) and recombinant human adenovirus type 5 (rAd5-S). The initial vaccine is rAd26-S and the booster vaccine, given 21 days later, is rAd5-S.
The researchers have used two different vectors to ensure that the booster dose remains effective even if the host develops antibodies against the vector of the first dose.
To ensure coverage even to remote areas, two formulations of the vaccine have been developed. The frozen vaccine would be introduced through the existing global supply chain, while the freeze-dried formulation would be used only in hard-to-reach regions.
Two sets of trials were carried out and both parts of the vaccine were tested in each. In the phase I of the trial, the vaccine was tested for safety. The phase II study then tested whether the vaccine elicited an immune response.
The trials were open, that is the participants knew they were receiving the vaccine. These took place in two hospitals in Russia and involved healthy adults aged 18-60 years. The frozen vaccine (Gam-COVID-Vac) was tested on both civilian and military volunteers while the freeze-dried vaccine (Gam-COVID-Vac-Lyo) was tested only on civilians.
There were 20 participants each in the frozen and freeze-dried vaccine groups.
All participants produced antibodies against the SARS-CoV-2 spike protein — more antibodies were elicited by frozen formulation than the freeze-dried formulation when tested on day 42 of the trial.
In addition, neutralising antibody responses occurred in all 40 participants in the phase II trials by day 42; here too, the frozen vaccine performed better.
The results of the trial were compared with natural immunity formed by infection with SARS-CoV-2, using convalescent plasma from 4,817 people who had recovered from mild or moderate COVID-19: It was found that the antibody response was better in vaccinated people.
Vaccination also elicited the same level of SARS-CoV-2 neutralising antibodies as in people who had recovered from COVID-19.
While the vaccine is being considered safe, it did cause side effects such as pain at the injection site (58 per cent), high temperature (50 per cent , headache (42 per cent , weakness (28 per cent), and muscle and joint pain (24 per cent). Most adverse events were mild, the researchers said.
They noted some limitations to their study such as the short follow-up period (42 days), predominance of male volunteers in the study and lack of comparison with placebo or control vaccines. In addition, they noted that despite planning to recruit healthy volunteers aged 18-60 years, in general, most volunteers recruited were in their 20s and 30s.
Explaining the next steps of their research, Alexander Gintsburg, professor with the N F Gamaleya National Research Centre for Epidemiology and Microbiology, Russia, said: “The phase III 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.”
Preclinical and clinical studies have made it possible to provisionally approve the vaccine under the current Decree of the Government of the Russian Federation of April 3, 2020 no 441.
The provisional licensure requires a large-scale study, allows vaccination in a consented general population in the context of a phase III trial, allows the vaccine to be brought into use in a population under strict pharmacovigilance, and to provide vaccination of risk groups.
Writing in a linked comment in the journal, Naor Bar-Zeev from the International Vaccine Access Center, Johns Hopkins Bloomberg School of Public Health, USA said the studies were encouraging but small.
The immunogenicity bodes well, although nothing can be inferred on immunogenicity in older age groups. Safety outcomes so far are reassuring, but studies to date are too small to address less common or rare serious adverse events, he said. He was not involved in the study.
Commenting on the study, Jacob Puliyel, Delhi-based paediatrician and an advocate of safe vaccines, said vaccines have to compete and show off their efficacy, safety and price efficiency. However, advance market commitments are being canvassed to circumvent real competition and it could leave countries with ineffective and harmful vaccines.
Instead, let the best formulation win whether it be from the United States, the United Kingdom, Russia or India, he added. The phase 3 would be the real test of the vaccine and decision of procurement should be made only after that, Puliyel said.