The Sputnik V Covid-19 vaccine from Russia offers 91.6% efficacy against symptomatic Covid-19 with a two-dose regimen according to the preliminary findings, published in The Lancet.
The phase 3 trial is based on analysis of data from nearly 20,000 participants, three-quarters of whom received the vaccine and one quarter received a placebo.
The trial included 2,144 participants older than 60 years, and vaccine efficacy was 91.8% in this group. The vaccine was well tolerated and safety data from 1,369 of these older adults found that the most common adverse events were flu-like symptoms and local reaction.
Serious adverse events (those requiring hospital admission) were rare in both the placebo (0.4% [23/5,435]) and vaccine (0.2% [45/16,427]) groups and none were considered associated with vaccination. Four deaths were reported in the trial, none of which were considered related to the vaccine. Most reported adverse events were mild, including flu-like symptoms, pain at injection site and weakness or low energy.
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 also weakened so that they cannot replicate in human cells and cannot cause disease. Adenoviral vector vaccines have been previously used, and their safety has been confirmed in several clinical studies.
Good tolerability profile in participants over 18 years
In this trial, participants were given one dose of rAd26-S, followed by a booster dose of rAd5-S 21 days later. The authors explain 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," says Dr Inna V Dolzhikova, co-lead author, 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.
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% [16/14,964) and 62 cases (1.3% [62/4,902]) in the placebo group - equivalent to an efficacy of 91.6%.
The vaccine induced a robust humoral response (also called antibody response) and cellular immune response (also called T-cell response) with data from 342 and 44 participants, respectively. Six of the 342 participants did not mount an immune response following vaccination, possibly due to older age or individual characteristics.
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.
Most of the reported adverse events (94% [7,485/7,966]) were mild (grade 1), and included flu-like illness, injection site reactions, headache, and asthenia (physical weakness or low energy). 451 were grade 2 (5.66%) and 30 were grade 3 (0.38%).
There were three episodes of serious adverse events in the placebo group (urolithiasis, sinusitis and flu-like illness) and three in the vaccine group (renal colic, deep vein thrombosis and extremity abscess). No association was found between the adverse events and vaccination.
Partially protective effect 16-18 days after a single-dose immunisation
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, University of Reading, and Professor Polly Roy, London School of Hygiene & Tropical Medicine, UK (who were not involved in the study), 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."