Russia has been badly hit by the COVID-19 pandemic, reporting over 3.85 million confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections to date.
Russia joined the vaccine race early on with the Sputnik V COVID-19 vaccine (Gam-COVID-Vac). Sputnik V, is a COVID-19 vaccine developed by the Gamaleya Research Institute of Epidemiology and Microbiology, and registered on August 11, 2020, by the Russian Ministry of Health as Gam-COVID-Vac. Sputnik V is an adenovirus viral vector vaccine. Gam-COVID-Vac was initially approved for distribution in Russia on the preliminary results of Phase I–II studies eventually published on September 4, 2020. The quick approval in early August of Gam-COVID-Vac was met with criticism in mass media. It precipitated discussions in the scientific community whether this decision was justified in the absence of robust scientific research confirming the vaccine's safety and efficacy.
On February 2, 2021, an interim analysis from the trial was published in The Lancet, indicating 91.6% efficacy without unusual side effects.
The phase 3 human trial is the last stage of clinical evaluation, showing how effective and safe a drug or vaccine is. In this case, the Gam- Sputnik V showed a consistent strong protective effect across all participant age groups.
The Gam-COVID-Vac vaccine
Sputnik V uses a heterologous recombinant adenovirus approach utilizing adenovirus 26 (Ad26) and adenovirus 5 (Ad5) as vectors for the expression of SARS-CoV-2 spike (S) protein.
Sputnik V uses a weakened virus to deliver small parts of a pathogen and induce an immune response. It is a vector vaccine based on adenovirus deoxyribonucleic acid (DNA), wherein the SARS-CoV-2 gene is integrated. The use of two varying stereotypes, which are administered 21 days apart, is intended to overcome any pre-existing adenovirus immunity in the population.
Unlike other vaccines against SARS-CoV-2, only Gam-COVID-Vac or Sputnik V uses this approach. It has the Ad5 and vesicular stomatitis virus as the carrier viruses. The aim of the vaccine is to prime-boost with two different vectors. The Gamaleya National Research Centre for Epidemiology and Microbiology has made a similar vaccine against Ebola.
The phase 3 trial
The late-stage trial or phase 3 trial involved 21,977 adults randomly assigned to the vaccine or placebo groups. Of these, 19,866 received two doses of the vaccine or placebo and were included in the primary outcome analysis.
At the screening, information on concomitant diseases and the COVID-19 risk group was entered into the participants' case report forms. High-risk individuals were those whose work involved interaction with patients who have COVID-19, the medium risk as those who interact with many people, such as social workers and shop assistants. The general risk group was those that have no additional risks linked to their work or activities.
The vaccine administered contains two vector components, rAd26-S and rAd5-S. The vaccine's full dose was 10¹¹ viral particles per dose for each recombinant adenovirus and administered as 0.5 ml per dose for intramuscular injection. Meanwhile, the placebo contains the vaccine buffer composition but without the recombinant adenoviruses.
The vaccine, wherein the first dose is the rAd26 and the second dose is the rAd5 or placebo, was administered intramuscularly into the deltoid muscle with a 21-day interval between doses. The participants received an initial dose of either the vaccine or a placebo, and then a booster dose 21 days later.
Trial findings
The study's primary outcome was the proportion of participants with COVID-19 confirmed by polymerase chain reaction (PCR) test from day 21 after receiving the initial dose. The secondary outcomes were the severity of COVID019, changes in antibody levels against SARS-CoV-2 glycoprotein S, changes in SARS-CoV-2 neutralizing antibody titers, proportion of participants with antibodies against SARS-CoV-2 N protein, and incidence and severity of adverse events.
Of the 14,964 people in the vaccine group, only 16 had developed symptomatic cases of COVID-19 after receiving the second dose of the vaccine. In the placebo group, however, 62 were infected in the 4,902-strong placebo group.
Hence, the vaccine efficacy was computed at 91.6 percent. The observed vaccine efficacy was greater than 87 percent in all age and sex subgroups. Also, vaccine efficacy was 91.8 percent in participants who are older than 60 years.
Further, the group did not receive reports of moderate or severe COVID-19 confirmed cases at least 21 days after the first dose, compared to 20 cases in the placebo group. This means that the vaccine efficacy against moderate or severe COVID-19 was 100 percent.
In terms of adverse effects, most of the reported cases were mild or grade 1. Meanwhile, 45 participants of the vaccine group and 23 of the placebo group had serious adverse events. None were considered linked to vaccination.
Notably, four deaths were recorded during the trial period, three in the vaccine group and one in the placebo group. However, none of these were considered related to the vaccine, as confirmed by the independent data monitoring committee (IDMC).
Vaccine roll-out
The interim analysis of the phase 3 trial of Gam-COVID-Vac has shown promising results. Along with the implementation of clinical trials in other countries, such as Belarus, India, and the United Arab Emirates, the vaccine has already been rolled out in Russia for public use, mainly in high-risk populations such as health workers and teachers. By January 23, 2021, more than 2 million doses of the vaccine have already been administered to the public.
The group has set to investigate a single-dose regimen of the vaccine and the clinical trial has been approved in January 2021 by the Regulator and Ethics committee in Russia.
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