By all accounts, the Covid-19 vaccine developed by Russia’s Gamaleya Institute, called Sputnik V, has looked really good. In a study published in The Lancet in February, the vaccine’s efficacy was 91.6%, putting it among the most effective vaccines for this pandemic in the world.
The technology used for Sputnik V is similar to the approach from Johnson & Johnson and AstraZeneca. It uses adenoviruses, essentially cold viruses, as vectors to ferry genetic instructions for the coronavirus-like protein to the body’s cells, causing the immune system to makes antibodies to this protein and thereby conferring protection.
Russia has emphasized that the vaccine costs less than $10 per dose and that it can be stored at 36-46 degrees Fahrenheit, making it easier to use around the world than the vaccines that have to be kept ultra cold. It says Sputnik V is already registered in more than 60 countries. But some regulators are now starting to ask questions about the vaccine. Brazil’s, in particular, this week rejected the vaccine, saying questions remained about its safety, manufacturing and development.
STAT sat down with Angela Rasmussen, a virologist and research scientist affiliated with the Georgetown Center for Global Health Science and Security and VIDO-InterVac at the University of Saskatchewan, to discuss.
This conversation has been lightly edited and condensed for clarity.
So what is your understanding of why Brazil rejected Sputnik V?
So the Sputnik V vaccine is actually two vaccines. It’s what’s called a heterologous dosing regimen. They start off with ad26 vector vaccine, that’s similar to what the Johnson & Johnson vaccine is, and then they follow that up with a booster dose of a vaccine that’s vectored with adenovirus 5. What they determined was that with the adenovirus component the virus can actually replicate and potentially cause downstream complications. The vaccine itself is designed to be replication incompetent, meaning that the adenovirus vectors are not going to replicate beyond expressing the spike protein that you’re developing immunity to.
These are essentially cold viruses and if there were replicating vector there, wouldn’t lots of people have gotten really bad colds during the clinical trials of Sputnik V?
Well, in this case, it’s not being delivered via the respiratory tract, so you wouldn’t necessarily expect these viruses to cause a respiratory disease. These are being delivered intramuscularly, which is not the way that adenoviruses are normally transmitted. That means there could be potentially unpredictable results of what could happen, particularly in recipients who might be immune compromised or have some type of immune dysfunction. There’s still a lot that’s not known about this particular issue. But in the Phase 3 clinical trials, at least in the data that was reported in The Lancet paper describing those trials, there wasn’t evidence of replication-competent virus in those vaccine preparations and normally making sure that there’s no replication-competent virus there should be part of any good-quality control program for manufacturing a vaccine.
To that point, there have been quality-control questions raised in other parts of the world too, specifically in Slovakia where regulators said a batch didn’t match the ones reviewed by The Lancet. Do you think that’s the same issue? Or is there something else also going on here with quality control?
So the situation in Slovakia — I have only seen reported that they they declined to allow a batch of vaccine in because it wasn’t consistent with what was reported in The Lancet, but I don’t know what the specific issue was. In general, this certainly gives me less confidence in the quality-control processes of this product going forward. If you are not getting the vaccine that you think you’re getting, then that means that the process is what’s the problem, not the vaccine. The Gamaleya Institute certainly has a long history of developing vaccines, including adenovirus vectored vaccine, so I don’t think that this is an issue with design. It doesn’t mean that the vaccine itself is inherently bad, it means that there are discrepancies in the manufacturing process.
So this vaccine has been licensed in dozens of countries around the world, at least on an emergency basis. Should people in the countries where it’s being used be worried if they’ve taken the vaccine?
It’s really hard to say right now because we just don’t have enough information about how commonly this is affecting all of the lots of vaccine that are being manufactured and distributed in those countries. This is definitely going to be something that the regulators in those countries are going to want to look into it. It is going to be really important to figure out what the risks are if somebody did get this vaccine that was replication competent and what that might mean in terms of vaccine safety.
For better or worse, global vaccine development has become a matter of soft power diplomacy between the U.S., China and Russia. How do you think the mounting concern about Sputnik V might affect geopolitics?
Well, I’m certainly a virologist and not a geopolitics expert, but you can imagine that Russia has presented the Sputnik V vaccine as something that they are doing out of altruism, and that’s their way of contributing to global health. And as you also know, there’s been a lot of discussion about the inequities in terms of rolling out vaccines globally. So this potentially deals a pretty serious blow, I would imagine, in terms of Russia taking a leadership role in making sure that vaccines are being distributed equitably to many countries around the world that desperately need them.
Speaking of Russia’s PR campaign around this vaccine, you’ve actually heard from the folks behind Sputnik V after you posted a detailed Twitter thread on what’s been found. What did they say?
They told me to stop spreading fake news. As I mentioned before, the Gamaleya Institute has a great reputation and their scientists are excellent, so I don’t think that this was intentional. But that said, I don’t consider it fake news when a country’s regulatory agency presents data showing that, in fact, there is replication-competent virus in the lots that they evaluated. That’s not fake news. That is an observation and that directly contradicts what their statement says. So I think that it would be a good idea for Sputnik to be cooperative with these regulatory agencies, because I don’t think that you can just point to a statement and say, oh, this is fake news.
Do you think the fact that the Brazilian regulators are saying, hold up here, we see something that we need to look more into and that Slovakia flagged that bad batch — do you think that’s a sign of the regulatory system globally is working? And do you worry that in the many countries that have been using the vaccine, maybe they don’t have that those same kinds of safeguards in place and people are more vulnerable there?
I think that’s definitely a possibility. It’s really hard in some cases to compare regulatory agencies around the world because apart from the WHO, which can make recommendations, there’s no such thing as a global regulatory agency. And certainly there are countries that really don’t have much in the way of a robust regulatory system. And in fact, you could argue that given that Russia authorized this vaccine before there was any type of clinical trial data, that that Russia might be among those countries. But I think overall, the WHO has said today that that they are still in the “back and forth phase” of evaluating the Sputnik V vaccine. I think that the WHO recommendation at least will carry a lot of weight.
I do think that this certainly shows that the Brazilian regulatory apparatus is intact at looking at this, I agree with everybody who said that the J&J pause was also evidence that the U.S. regulatory system is robust as well. I should add that those severe side effects observed with Johnson & Johnson, and perhaps also with AstraZeneca, aren’t necessarily the same problem with the Sputnik vaccine. This is a different issue. To my knowledge, there has never been an issue with J&J or AstraZeneca vaccines being given that were problematic in terms of their manufacturing or quality control. And in fact, the doses of Johnson & Johnson where there were quality control problems were discarded prior to those vaccines ever making it to market. Again, showing that our regulatory systems are robust and working.