Sputnik V launched again!
The SARS Cov-19 vaccine developed by the Gamaleya research institute, Russia
Background and Controversy
On August 12th President Vladimir Putin made a huge announcement to the world calming that Russia has developed a successful vaccine for SARS-Cov19 despite having no published research papers on the clinical trials of the vaccine. Russians have decided to name it “Sputnik V”, a tribute to the Soviet Era when Russia launched a successful orbital satellite in 1957. The global community had mixed opinions about using this for a mass vaccination as there were no published work on it. This vaccine was controversial as the trials were much smaller and quicker than other proposed vaccines. Russians said that their vaccine was created so quickly because it was based on a previously developed Russian Ebola vaccine. However, in August the Russian authorities said that they would start the mass vaccination in October. In late September details about the phase I and II was published in the Lancet giving the global community some data of the vaccine for the first time.
How it works
“Sputnik V” is being developed as a two-dose vaccine using two human recombinant adenovirus vectors; rAd5 and rAd26. These are known to cause respiratory infections, but they have been inactivated so that they would not replicate in the body hence making it unharmful. These inactivated adenoviruses function as vectors as they are modified to carry the gene that encodes the spike protein of the coronaviral envelop. Prevention of SARS-CoV-2 infection might be achieved by targeting the spike protein (glycoprotein S), which interacts with the cell membrane and enables entry of SARS-CoV-2 into the cell. Blocking this interaction decreases chances that the virus has to enter the cell. The hope is that these vectors would trick the immune system into producing antibodies and memory cells so that they can fight the real virus if it enters the body.
A full dose of the vaccine was 10¹¹ viral particles per dose for both recombinant adenoviruses. The dose was set based on findings of preclinical studies (unpublished data). The vaccine was manufactured as two formulations, frozen and lyophilized (freeze dried into a powder). The frozen vaccine has a volume of 0·5 mL (per dose) and the lyophilized vaccine needs to be reconstituted in 1·0 mL of sterile water for injection (per dose).
There have been several experimental vaccines and drugs that use human adenovirus vectors but none has been commercially approved for use in people. Sputnik V is also a two-dose regimen, meaning that individual shots are dispensed three weeks apart. The argument is that the second dose acts as a booster shot and the developers has said the use of two vectors is what differentiates the Russian vaccine from the other adenovirus-based approaches. The challenge to use human adenovirus as a vector is that because they commonly infect people, many have pre-existing immunity to the virus and so antibodies may block the vector even before it infiltrates cells and synthesizes proteins that can specifically induce immune cells specific to the coronavirus. The rAd5 has been previously used to produce vaccines as well as drugs against other diseases including HIV, but that didn’t work.
The Trials (Stage 1 and 2)
The developers have done two open, phase 1 and 2 non-randomized studies at hospitals in Russia. For each study, 120 healthy adult volunteers (aged 18–60 years) were preselected to be included in the volunteer register; all adults provided signed informed consent to be included in this database for study participation. The trials included adult volunteers of both sexes with a body-mass index of 18·5–30·0 kg/m², who had a negative PCR and did not have antibodies to SARS-CoV-2, and who had no history of COVID-19 or contact with patients with COVID-19. Volunteers had no infectious diseases at the time of vaccination and for 14 days before vaccination, and they did not receive any other vaccinations within 30 days of participation in the study.
To compare post-vaccination immunity with natural immunity that forms during infection with SARS-CoV-2, we obtained convalescent plasma from blood samples of 4817 people from Moscow who had recovered after COVID-19 (between March 29 and Aug 11, 2020). Convalescent plasma was obtained from people who had had a laboratory-confirmed COVID-19 diagnosis, who had been recovered for at least 2 weeks, and who had tested negative by PCR twice.
During phase 1 of both studies (administration of either rAd26-S or rAd5-S alone), SARS-CoV-2 antibodies were detected on day 14 in 88·9% of participants after administration of rAd26-S and in 84·2% of participants after administration of rAd5-S (combined data for both the lyophilized and frozen vaccine formulations); beginning from day 21, SARS-CoV-2 antibodies were detected in 100% of vaccinated participants.
During phase 2, SARS-CoV-2 antibodies were detected in 85·0% of participants on day 14 (after priming with rAd26-S) and in 100% of participants from day 21. Boosting with rAd5-S led to an increase in SARS-CoV-2 antibodies.
Analysis of neutralizing antibodies to SARS-CoV-2 showed that only administration of both rAd26-S and rAd5–2 led to production of neutralizing antibodies in 100% of participants, whereas administration of only rAd26-S led to a seroconversion rate of 61·1% (combined data for both the lyophilized and frozen vaccine formulations). Comparing data for antibody responses to SARS-CoV-2 at days 28 and 42 with data for antibody responses in convalescent plasma showed that post-vaccination antibody concentrations were significantly higher than were after COVID-19 infection, whereas significant differences in neutralizing antibodies were not seen.
The Side effects
In both studies, systemic and local reactions and changes in laboratory variables were among the unfavorable events reported. The most common systemic and local reactions were pain at injection site (44 [58%]), hyperthermia (38 [50%]), headache (32 [42%]), asthenia (21 [28%]), and muscle and joint pain (18 [24%]). Most systemic and local reactions were mild. Changes in laboratory variables were mild and only lasted for a short time.
In volunteers who received both vaccine components (rAd26-S and rAd5-S), most unfavourable events occurred after the second vaccination. No such events, either during phase 1 or phase 2, led to withdrawal of a participant from the study or withdrawal of study drug. In general, disadvantageous events identified during phase 1 and phase 2 of both studies were characteristic of other vaccines (particularly those based on recombinant viral vectors). No serious adverse events were reported and all participants were clinically well throughout the study.
