Putting Sputnik V in the Spotlight
By Sadira Sittampalam
Ceylon Today Features
On 11 August, Vladimir Putin announced Russian health agencies had approved the use of the world’s first vaccine for widespread use against COVID-19. They named it Sputnik V (yes, really) and while it is potentially really good news, a lot of experts are still quite sceptical as to whether the vaccine actually works, mainly because it has been tested in an unusual way.
Since vaccines are technically drugs, they are supposed to get approved for use by regulatory drug agencies. The people who come up with the vaccine are meant to prove themselves and justify their vaccine publicly with a very specific set of scientific tests. This is usually why vaccines are considered, as a whole, so safe and effective, but this is not what happened with this new Russian vaccine. The developers of the vaccine claimed that their vaccine was successful before even starting any kind of testing that would prove such a thing and only published some seemingly modified version of their results last week.
Drug trials in humans are also known as clinical trials and are typically organised into four or five stages. Each builds on the previous ones, however, they can sometimes be combined. In the US they are named Phases 0, I, II, III, and IV - but phase IV happens after the drug enters the market. Phases 0 and I are generally short, small studies that essentially are intended to make sure that the drug does the very basics of what it is meant to do and doesn’t show any majorly adverse reactions in the process. This is usually the first time this specific drug would have been given to people, so researchers are focused on watching out for any and all negative side effects. They also try and figure out the dosage and what would be best.
A Chinese company called CanSino started their Phase 1 trials for their COVID-19 vaccine all the way in March. They gave 108 participants a low, medium or high dose of the vaccine. They noticed that a few people showed mild to moderate side effects like fatigue or headaches, however, for the most part, the vaccine appeared safe enough to use in people, and therefore, it moved into Phase II clinical trials. This stage is where scientists continued to look for any adverse effects and evaluated their dosing, while also questioning more closely at whether the vaccine actually did anything. This stage is also where participant numbers increase so as to get a better understanding of how the vaccine can affect a wide range of people. So CanSino’s Phase II tested two different doses against a placebo in about 500 participants. As hoped, vaccinated participants started producing antibodies that could neutralise the virus while also having a few other promising immune responses as well.
Going back to the Russian trials, two combined Phase I and II trials for Sputnik V were only listed online as ‘complete’ for three weeks after the vaccine had been announced, with no actual data being published. It was only a week ago that some of the results had been revealed. The data available about how the vaccine works or how those trials went along with everything we know about the vaccine also only comes from the Russian government and the researchers involved, which is problematic, to say the least. However, this gets even worse as while the data claims that these two phases did actually go well, these positive results seem to raise a few concerns as some data appears to repeat in a way that defies coincidence, hinting that some of the data was falsified. Furthermore, data from only those phases do not guarantee the vaccine will work in the real world. Immune reactions are complicated and Phase II trials don’t actually end up testing whether a vaccine prevents people from getting sick. That doesn’t happen until at least Phase III.
These trials are typically hundreds, thousands or even tens of thousands of participants larger, in order to let the researchers see if or how many people catch the disease after getting the vaccine. Thus, a good amount of people are needed in order to make sure a significant percentage would eventually be exposed to the virus in their daily lives. This takes quite a bit of time which is also why Phase II trials usually take more than a year to finish. This phase is also to spot any potential rare or serious adverse events that could occur in every ten thousand vaccinations or so - and is especially vital as the end goal would be to vaccinate hundreds of millions of people. This is why Phase III trials are really important, both as measures of how well the vaccine would work and how safe it really is with the large numbers and extended gestation period key to all of that.
Since Putin’s Sputnik V announcement, it hasn’t really been made clear whether Russia was planning to start Phase III trials. The details are quite fuzzy and there are certain sources that say the vaccine’s approval is dependent on positive Phase II results and that those trials have either started or will start soon. Nevertheless, there are reports that the vaccine is shipping out to all regions of Russia on 14 September, even though many scientists note that no definitive conclusions can be drawn without the full data from the trial and therefore request that the study authors release all of the data from the experiments.
However, Russia isn’t the only country taking risks like this or skipping steps in hopes of delivering a vaccine as soon as possible. In the US, a company called Moderna launched into human trials for their vaccine before completing pre-clinical trials in animals. Then, they went into Phase III before finishing phase II or publishing the full results from Phase I. A pharmaceutical company Pfizer also announced that they may apply for US’s FDA (Food and Drug Administration) approval for their vaccine in October even though they are still in Phase II and III trials. While it would be a something that has never been done before for the FDA to grant approval, the FDA commissioner said that they might consider an emergency use authorisation if a company were to submit compelling paperwork before the end of clinical trials. Nevertheless, vaccine trials in America and even other countries have still collected significantly more data than Russia, even though Russia is the first country to approve of a COVID-19 vaccine.
Sputnik V is an adenovirus, a common cold virus, called Ad5 and Ad26 that are made safe and that are incapable of growing in the body. The only function of this virus is to deliver the genetic code of one of the novel Coronavirus proteins, called the spike protein, into a cell. By injecting people with these modified adenoviruses, the immune system is stimulated to respond to the spike protein and hopefully to continue to respond to it for many years into the future, so that if the person if exposed to COVID-19 they immune system will know how to respond to it. This type of vaccine is not new to Sputnik V though, as even CanSinoa and a few other research companies have been using it as it has, in general, been proven to be safe amongst healthy people within the ages 18-60. The real question is whether the Russian variation of this type of vaccine will actually protect against COVID-19 and whether this vaccine is equally safe, as it has only been tested out in 76 volunteers. Unfortunately, this is a question that will only be answered in time as the vaccine is rolled out around Russia. More than a third of drugs that do well in Phases I and II fail in Phase II. Thus, while it is possible that this gamble may pay off, it could also not work. It could even prove to be truly harmful to a lot of people, ruining whatever trust people have in vaccines.