Updated 3 Feb 2021 to reflect peer reviewed data on Sputnik. Note this blog was originally published 21 Aug – a month before the developers of this vaccine began recruiting into a phase III trial and a month before the early Phase I-II data was published so I absolutely stand by my critique. As of today Phase III data has been published and the trial appropriately registered. The first data includes over 20,000 randomised adults (3:1 so more received the vaccine) over 18-years. The efficacy against COVID disease was estimated to be 91.6% after two doses and 73.1% after one dose. This vaccine appears effective and there were no safety concerns identified. Pity they failed to be transparent and appeared to be cutting corners early on.
Russia are deploying a COVID-19 vaccine to its people without knowing if it works or if it is safe. They also appear to be taking advance orders for doses from other countries. It is almost hard to know where to start with why this is so wrong. Reckless, unethical, and now utterly reliant on dumb luck.
In 2020 it is not hard to come up with a vaccine candidate. Just 45 days after China released the SARS-CoV-2 genome an RNA vaccine was ready to be administered to the first humans. There are over 175 COVID-19 vaccine candidates of all kinds under development so Russia knocking off a candidate is not all that impressive. Sticking a needle into people in not very impressive either. The real challenges come with assessing the vaccine candidate for efficacy and safety – ethically – and that takes time, lots of participants, rigorous regulatory processes, and clear informed consent from the participants (see my blogs on these processes here and here.
What we know about the Russian COVID-19 vaccine
It is hard to find information about this vaccine but from the Registration Certificate based on 38 people it would seem to indicate a prime-boost strategy with two viral vector vaccines. This strategy involves two doses administered at different times, with each dose using a slightly different viral vector. The viral vectors are basically benign viruses that infect humans. Essentially the first dose is like the Johnson and Johnson candidate, which uses adenovirus-26, and the second dose is like the Chinese CanSino Biologics, candidate which uses Adenovirus-5. I assume the Russians are using the different viral templates to avoid the potential of existing immunity interfering with the immune response. Just guessing here.
Reports suggest the immune responses and reaction profiles from 76 volunteers are in line with the Johnson and Johnson and CanSino candidates, although as it is not actually published in a peer reviewed forum it is hard to judge. And this appears to be the sum total of data upon which this vaccine was registered for use in Russia. Yikes!! I am practically having kittens!
Here is a schematic of how a viral vector vaccine works from Nature.
Examples of similar vaccines – doing it right
Speaking of COVID-19 viral vector vaccines as comparisons you can see a recent publication on the Chinese CanSino candidate here in the Lancet, with over 500 participants in a Phase II trial, they are now in Phase III. Here is a publication on the Johnson and Johnson candidate which is in earlier stages; and here is a publication on the Oxford vaccine describing results from over 1000 participants, this vaccine is also now in Phase III trials now.
Doing it wrong
Putin claims the Russian vaccine has shown efficacy and safety.
“I know that it works quite effectively, forms strong immunity, and I repeat, it has passed all the needed checks,” Putin said
This cannot possibly be true because to prove efficacy you need a very large placebo-controlled trial with enough people and enough time to prove that the risk of disease is lower in the vaccinated group (in this case tens of thousands over several months). As for safety, I would not consider a vaccine had a robust safety profile until there was quality post licensure data from at least a million people (like our routinely used vaccines do). Russia’s own head of Clinical Trials organisation acknowledges that Russia’s ability to monitor safety “is not the best”.
So, if something goes wrong the Russians probably have limited ability to pick it up promptly. Post licensure surveillance of vaccines is a science in itself that needs resource and robust systems. If something goes wrong then the entire global effort to develop safe and effective vaccines against COVID-19 can be damaged by association.
To put this in context, I would want to see data from trials that have included in the order of 30,000 participants, most of them randomised to vaccine or placebo, before putting my arm out. Fortunately, this will be the standard that most countries demand. Fortunately, there are some promising COVID-19 vaccine candidates well into such trials such as the Oxford viral vector and the RNA vaccine candidates. For my part, I will wait for those.