LONDON – Results from two non-randomized phase I/II trials of the Russian COVID-19 vaccine Sputnik V that recently received conditional regulatory approval show both a frozen and a freeze-dried formulation of the two-shot vaccine had a good safety profile and induced antibody responses in all 76 participants within 21 days.

The results were published today in a peer reviewed paper in The Lancet, following controversy that although Russian President Vladimir Putin had announced the conditional licensing of the vaccine on Aug. 11, no data had been made available for scientific scrutiny.

In the phase I part of each trial, the individual components of the vaccine, recombinant human adenovirus type 26 (rAd26-S) and recombinant human adenovirus type 5 (rAd5-S), engineered to express the spike protein by which the SARS-CoV-2 virus enters human cells, were assessed for safety.

Following this, the phase II tested whether the vaccine elicited an immune response, with rAd26-S administered first, with rAd5-S following 21 days later.

All 40 participants in the phase II trials produced antibodies against the SARS-CoV-2 spike protein on day 42. In addition, neutralizing antibody responses occurred in all 40 individuals.

Comparing the antibody responses from the vaccination and from natural infection, using plasma from 4,817 people who had recovered from mild or moderate COVID-19, the authors say responses from vaccination appear to be higher. Vaccination also elicited the same level of SARS-CoV-2 neutralizing antibodies as seen in people who had recovered from COVID-19.

T-cell responses occurred in all participants in the phase II trials within 28 days of vaccination, including the generation of T-helper (CD4) cells and T-killer (CD8) cells.

The trials, which took place in two hospitals in Russia, were open-label and non-randomized. The healthy adults aged 18-60 years who took part in the study self-isolated as soon as they were registered to take part and remained in hospital for 28 days after first vaccination.

The frozen vaccine (Gam-COVID-Vac) was tested in a branch of Burdenko Hospital, an agency of the Ministry of Defense, and involved both civilian and military volunteers. In the freeze-dried vaccine (Gam-COVID-Vac-Lyo) trial at Sechenov University, all volunteers were civilians.

The trials were funded by the Ministry of Health of the Russian Federation and conducted by researchers from the Ministry of Health and the Ministry of Defense.

Most adverse events were mild, and no serious adverse events were detected within 42 days of vaccination. The authors note the observed adverse events are characteristic of those seen with other recombinant viral vectors.

The strategy of using two different adenoviral vectors was adopted is a bid to avoid the immune system becoming immune to the vector, said author Denis Logunov of N F Gamaleya National Research Center for Epidemiology and Microbiology. “To form a powerful immune response against SARS-CoV-2, it is important that a booster vaccination is provided. However, booster vaccinations that use the same adenovirus vector might not produce an effective response, because the immune system may recognize and attack the vector,” Logunov said.

In the event, despite neutralizing antibody responses against the adenovirus vectors, the antibody response to the SARS-CoV-2 spike protein was not affected, according to Logunov. In addition, neutralizing antibodies against rAd26 did not interfere with rAd5, or vice versa.

The researchers suggest using different adenovirus vectors is an effective approach to elicit a robust immune response and circumvent the immune reaction to the first viral vector, but say more research is needed to confirm this.

Apart from the obvious shortcoming that there was no placebo arm, the authors note other limitations of the study, including the short 42-day follow-up. It was a small study and some of the phase I included only male volunteers, and despite planning to recruit people aged 18–60 years, most volunteers were in their 20s and 30s.

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, the authors say.

Researcher Alexander Gintsburg also of the N F Gamaleya National Research Center for Epidemiology and Microbiology, said the “unprecedented measures” taken to develop a COVID-19 vaccine in Russia 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 license allows the vaccine to be used under strict pharmacovigilance measures in at risk populations. It also requires a large-scale phase III study be carried out, said Gintsburg. “The phase III clinical trial of our vaccine was approved on 26 August 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,” he said.

The studies, “are encouraging but small” said Naor Bar-Zeev of the International Vaccine Access Center at Johns Hopkins Bloomberg School of Public Health, in a commentary accompanying the trial results. “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 COVID-19 vaccines are safe will be crucial, not only for vaccine acceptance but also for trust in vaccination broadly, Bar-Zeev said. “Safety outcomes up to now are reassuring, but studies to date are too small to address less common, or rare serious adverse events.”