Russian Sputnik vaccine demonstrates 91.6% efficacy

Preliminary efficacy and safety results from the Russian COVID-19 phase 3 vaccine trial suggest that the two-dose regimen of the adenovirus-based vaccine (Gam-COVID-Vac) is 91.6% efficacious against symptomatic COVID-19.

Published in The Lancet, the trial was conducted across 25 hospitals and polyclinics in Moscow, Russia. The primary interim efficacy analysis reports on results from almost 20,000 participants: 14,964 in the vaccine group and 4902 in the placebo group. The ongoing trial is aiming to include 40,000 participants.

No serious adverse events were deemed to be associated with vaccination, with most reported adverse events being mild, including flu-like symptoms, pain at injection site and weakness or low energy. A sub-analysis of 2000 adults older than 60 years suggests the vaccine is similarly effective and well tolerated in this group.

The Gam-COVID-Vac is a two-part vaccine that includes two adenovirus vectors — recombinant human adenovirus type 26 (rAd26-S) and recombinant human adenovirus type 5 (rAd5-S) — which have been modified to express the SARS-CoV-2 spike protein. The adenoviruses are weakened so that they cannot replicate in human cells and cannot cause disease.

Trial participants were given one dose of rAd26-S, followed by a booster dose of rAd5-S 21 days later. The authors explained that using a different adenovirus vector for the booster vaccination may help create a more powerful immune response compared with using the same vector twice, as it minimises the risk of the immune system developing resistance to the initial vector.

“Our interim analysis of the randomised, controlled, phase 3 trial of Gam-COVID-Vac in Russia has shown high efficacy, immunogenicity, and a good tolerability profile in participants aged 18 years or older,” said Dr Inna V Dolzhikova, co-lead author from the Gamaleya National Research Centre for Epidemiology and Microbiology, Russia.

Worldwide, 64 candidate COVID-19 vaccines are currently in clinical assessment (including 13 vaccine candidates at phase 3) and 173 vaccines are in preclinical analyses. Phase 3 candidate vaccines include a variety of vaccine platforms, such as vector vaccines, mRNA vaccines, inactivated vaccines and adjuvanted recombinant protein nanoparticles.

“Stopping the COVID-19 pandemic requires the introduction of different vaccines based on different mechanisms of action to cover diverse global health demands. Our vaccine, along with other SARS-CoV-2 vaccines, helps to diversify the world SARS-CoV-2 vaccine pipeline,” co-lead author Dr Denis Logunov said.

From 21 days after receiving the first dose (the day of dose 2), 16 cases of symptomatic COVID-19 were confirmed in the vaccine group (0.1%) and 62 cases (1.3%) in the placebo group — equivalent to an efficacy of 91.6%.

The authors note that because COVID-19 cases were detected only when participants self-reported symptoms (followed by a PCR test), the efficacy analysis only includes symptomatic cases of COVID-19, and further research is needed to understand the efficacy of the vaccine on asymptomatic COVID-19, and transmission. Furthermore, median follow-up was 48 days from the first dose, so the study cannot assess the full duration of protection.

During the trial, four deaths were recorded — three (<0.1%) in the vaccine group and one (<0.1%) in the placebo group. In the vaccine group, one death was associated with a fracture. Two had underlying conditions and developed symptoms of COVID-19 4–5 days after the first dose of the vaccine. Based on the incubation period of the disease, both participants were deemed to have already been infected before inclusion in the trial, despite a negative PCR test. The death in the placebo group was associated with a stroke. None of the deaths were deemed to be associated with vaccination.

As part of their secondary analyses, the authors explored the efficacy of the vaccine against moderate or severe COVID-19. At 21 days after the first dose, there were no cases of moderate or severe COVID-19 in the vaccine group and 20 cases in the placebo group, equivalent to an efficacy of 100% against moderate or severe COVID-19.

Although the study was not designed to assess the efficacy of a single-dose regimen, the findings hint to the early onset of a partially protective effect 16–18 days after a single-dose immunisation. From day 15–21, efficacy against moderate or severe COVID-19 was 73.6%, but further research is required to draw any robust conclusions from these observations. The research team have recently received approval to investigate the effectiveness of a single-dose regimen of the vaccine.

Writing in a linked Comment, Professor Ian Jones from the University of Reading and Professor Polly Roy from the London School of Hygiene & Tropical Medicine said, “The development of the Sputnik V vaccine has been criticised for unseemly haste, corner cutting, and an absence of transparency. But the outcome reported here is clear and the scientific principle of vaccination is demonstrated, which means another vaccine can now join the fight to reduce the incidence of COVID-19.”

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