The story so far: On September 16, Hyderabad-based Dr. Reddy’s Laboratories announced that it had signed an agreement with the Russian Direct Investment Fund (RDIF) to conduct large human trials (Phase-3) of Sputnik V. A candidate vaccine for COVID-19 , it has been developed by Russia’s Gamaleya Research Institute and piloted by the RDIF, the country’s sovereign wealth fund. If these trials are successful and the vaccine is proved to be safe, Russia has committed itself to supplying 100 million doses to India through Dr. Reddy’s.
What do we know about Sputnik V?
Much like the launch of the Sputnik-1 satellite in 1957 heralded the Space Age, Russia claims the vaccine candidate will “reinvigorate” vaccine development and a potential solution to the coronavirus pandemic. Sputnik V is being developed as a two-dose vaccine using two human recombinant adenovirus vectors — rAd5 and rAd26 — known to cause respiratory infections. These vectors have been modified to not replicate in the body. These inactivated vectors are also tweaked to carry the ‘S gene’ that encodes the ‘spike protein’ of the coronavirus. The hope is that these vectors will inveigle themselves into a small number of the body’s cells, trick the body into registering the coronavirus’ spike protein and thus activate the immune system into producing specialised ‘T’ cells that can neutralise the affected cells. Once this happens the immune system is expected to produce antibodies as well as ‘memory B cells’, which can produce the right offensive cells when needed to neutralise future SARS-CoV-2 infections the body may encounter.
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Is this a proven approach?
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 Gamaleya has said the use of two vectors is what differentiates the Russian vaccine from the other adenovirus-based approaches. CanSino Biologics of China and the vaccine being developed by Oxford University (ChAdOx1) are also based on adenovirus platforms, except that the Oxford candidate uses an adenovirus vector that is known to infect chimpanzees.
What are the key challenges?
The challenge with using human adenoviruses 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 synthesises 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. CanSino Biologics used the same vector to make a vaccine against the Ebola virus during an outbreak in West Africa. The vaccine was tested in people but wasn’t licensed, though it reportedly induced a short-term antibody response in those who were inoculated. Researchers suggested that the pre-existing rAd5 immunity in people may have blunted the response. An adenovirus-based vaccine has been commercially licensed for rabies. The second vector being used by Sputnik V, rAd26, is a rarer adenovirus and is devised to work as a backup or a booster to stimulate a stronger response. The risks are that too strong a response may cause severe adverse reactions.
Has Russia started large trials of Sputnik V?
Earlier this month, Russia said it had begun testing the vaccine in the country among 40,000 volunteers as part of its large Phase-3 trials. Experience from Phase-1 and Phase-2 in a smaller group of volunteers and designed to test for safety and efficacy suggested that it was promising enough to progress onto the larger trials. The most controversial aspect of Sputnik V is that it has already been preapproved by the country’s health agency even before Phase-1 and 2 trial results were published. According to health experts, this indicated that speed, and not safety, was being prioritised. Pharmaceutical companies in the U.S. and Europe have pledged not to approach regulators before Phase-3 trials concluded. As of September 19, there were no details of how Dr. Reddy’s planned to go about conducting the trials in India.