International delivery of the Sputnik V vaccine will start in January

Russia and India have been engaging on several fronts—strategic, nuclear, engineering—in the past. On the medical side, this is probably the first engagement. What are your thoughts on this important area of collaboration?

India and Russia have enjoyed what can be called a special relationship for many decades. As fellow BRICS and G20 members, the two countries often see eye to eye when it comes to many global challenges. There have been numerous cases of our collaboration in various spheres, from military and finance to energy and construction among many others. It is true that pharmaceutical industry has hardly been at the centre of Indian-Russian economic ties and I hope that our joint struggle against Covid-19 will help change that as we overcome the social and economic disruption caused by the pandemic. Russia’s long-standing track record as medical pioneers and India’s world-class production and export capabilities are a great match.

We are absolutely confident in India’s ability to manufacture the vaccine given that the country is already producing about 60 per cent of all vaccines globally. Its production capabilities are unmatched. Together we will able to meet the demand, that is the need of the hour as both of our countries are among the most affected by Covid-19 globally.

Please explain in what ways you will be engaging with Indian manufacturers and suppliers for the Covid-19 vaccine? What sort of engagements with the drug regulator and manufacturers are lined up for you in the coming months?
In September, a partnership with Dr Reddy’s was formed to conduct clinical trials of Sputnik V in India and to work together on its local distribution. As part of the partnership, 100 million doses of the vaccine will be supplied to Dr Reddy’s upon regulatory approval in India. Dr Reddy has been working in Russia for over 25 years and is a well-established and respected player on the pharmaceutical market here.

We have also signed agreements with the manufacturers in India to produce the vaccine locally. According to our deal with Hetero, one of India’s leading pharma companies and the world’s biggest maker of anti-retroviral drugs, which we announced on November 27, the company will be producing 100 million doses of the Sputnik V vaccine per year starting from 2021.

Given that India is among the nations worst-hit by the pandemic, we are hopeful that our vaccine, based on human adenovirus dual vector platform, will help stop the spread of Covid-19 in the near future. As the Drug Controller General of India has allowed us to conduct adaptive phase II-III human clinical trial for our vaccine, we believe we will secure all the regulatory approvals to distribute the vaccine in India.

In what ways would you say Sputnik V is different from the other front-runner candidates including Moderna, Pfizer and Oxford-Astra Zeneca?
There are several key differences. Let me highlight the most important ones:

1. Proven Platform
Sputnik V uses a proven, two-vector human adenovirus-based platform that has been adapted from the two-vector platform used in 2015 to develop a vaccine against Ebola (like Sputnik, it was designed by the Gamaleya Research Centre). The human adenoviral vectors platform has also been used to produce Gendicine, a drug for the treatment of cancer, which has been used in China for more than 12 years and a vaccine against Ebola by J&J. Other platforms, such as the chimpanzee adenovirus-based one used by AstraZeneca, or mRNA-based ones from Moderna and Pfizer, do not have long-term safety studies.

2. Safety and Efficacy

Even before this global health crisis began, the efficacy of the human adenoviral vector platform had been widely proven for non-COVID-19 vaccines, including by some of the world’s largest pharmaceutical companies. More than 250 clinical trials and 75 international publications confirm the safety of vaccines and medicines that are based on human adenoviral vectors.

This was confirmed with the results of phases I-II clinical trials of Sputnik V, published in the reputable peer-reviewed medical journal The Lancet that showed no serious or severe adverse events (Grade 3). Phase III preliminary results based on 18,794 volunteers 28 days after they received the first immunisation (seven days after the second one) showed the vaccine’s efficacy at 91.4 per cent. This compares to a minimum 50 per cent efficacy rate set out by the Indian Council of Medical Research (ICMR) and the World Health Organisation (WHO) alike. Preliminary data on volunteers on the 42nd day after the first dose (equivalent to 21 days after the second dose), when they have already formed a stable immune response, indicates the efficacy rate of the vaccine is above 95 per cent.

As of November 24, there were no unexpected adverse events during the trials. For comparison, in the recently released preliminary phase III results, AstraZeneca showed full dosage efficacy at only 62 per cent for its chimpanzee adenovirus candidate vaccine. Sputnik V does not contain live human adenoviruses, instead it uses human adenoviral ‘vectors’ that are unable to reproduce and are completely safe for health. Furthermore, Sputnik V does not contain the SARS-CoV-2 virus itself, so it is impossible to get Covid-19 as a result of the vaccination.

3. Storage
Storage and logistic remain the biggest challenges in most countries, particularly in large developing nations such as India. To address them, there are two forms of the Sputnik V vaccine—the liquid one, which would have to be stored at -18°C, and the lyophilised (freeze dried) one, which can be stored at 2°C to 8°C. The lyophilised form was developed especially for the transportation of the vaccine to remote places. This compares to temperature of -70°C  that some other vaccines need to be stored at. RDIF and partners have already launched production of the lyophilised form of the vaccine.

4. Dosage
Two doses of Sputnik V are required three weeks apart. It makes the body develop antibodies against S-protein of the virus post administration. It is at this level when the immunity is triggered against this protein that the coronavirus is prevented from entering cells in the body, making us immune to the infection.

Sputnik V is the only late-stage adenovirus-based Covid-19 vaccine candidate to use two different vectors for different injections—human adenovirus types Ad5 and Ad26. In vaccines that use the same vector in two injections, the immune system may launch defence mechanisms against the second injection making the vaccine less effective.

5. Cost
The cost of one dose of the Sputnik V vaccine for international markets will be less than $10. As Sputnik V is a two-dose vaccine, it will be at least twice as cheap as mRNA vaccines with similar efficacy levels. Vaccination with Sputnik V will be free of charge for Russian citizens.

How are the phase III trials in Russia progressing?
There are currently over 40,000 volunteers taking part in the double-blind, randomised, placebo-controlled phase III of Sputnik V clinical trials. Over 23,000 have been vaccinated with the first dose and more than 19,000 with both doses of the vaccine. In addition, frontline medical staff in the 'red zones' of Russian hospitals are already being vaccinated as part of the civil circulation of the vaccine. The interim research data will be published by the Gamaleya Center team in one of the leading international peer-reviewed medical journals.

Following the completion of phase III clinical trials of the Sputnik V vaccine, Gamaleya Center will provide access to the full clinical trial report.

RDIF is actively working with Russian and foreign manufacturers to increase production of the Sputnik V vaccine.

Data from phase I/II studies of Sputnik V was debated in The Lancet. What are your key arguments?
There is no question that all vaccines should, as a rule, be subject to the most rigorous scrutiny by the scientific community. Please note that The Lancet, one of the world’s oldest and well-known medical journals, has rigorous standards involving a requirement for publications to be peer-reviewed. Obviously, that applied to the Russian Covid-19 vaccine story based on phases I-II clinical trials published in September.

Nevertheless, a group of readers in an open letter to The Lancet raised concerns about the validity of the data presented. All these concerns were addressed by the article’s leading author, Dr Logunov, in a response published on The Lancet’s website. He emphasised that all the presented data were obtained in experiments within the required timeframe and double checked and attributed the coincidences to discreteness of the data and the small number of participants in the groups.

We are now close to a couple of vaccine candidates getting early, emergency approvals. Public health experts are pushing for transparency from vaccine developers. What are the challenges in early vaccine approvals?
The world is in urgent need of top-quality vaccines against Covid-19. While the experts, governments, and agencies across the globe have fast-tracked the development process to a degree, virologists have a sense of responsibility to provide safest and efficient vaccines. The process is streamlined and every vaccine must go through the litmus test and prove its safety and efficacy during clinical trials. We are abiding by the rules and regulations. Sputnik V is now in Phase III and we believe that the vaccine will reach the world very soon.

I think the biggest challenges, that I touched upon earlier, are production and distribution. Universal vaccination will require billions of doses and that is no small feat for the global pharmaceutical industry. Countries around the world are already lining up to make sure they will be at the beginning of the queue once production commences. Equally important is delivery as some vaccine types require special equipment to be stored and transported. That could be a challenge even for developed countries with top-notch medical facilities at their disposal not to mention developing countries.

What are your production plans for Sputnik V?
We have received applications for more than 1.2 billion doses of the vaccine from more than 50 countries. A significant amount of the vaccine will be produced outside of Russia, including in India, China, South Korea and Brazil. Next year, vaccine production by foreign manufacturers contracted by RDIF will significantly exceed the volume produced in Russia. According to the agreements already signed, the vaccine will be manufactured internationally for 500 million people per year from 2021.

RDIF is currently considering additional applications from a number of countries. Based on the unprecedented interest we are seeing, that number could be increased even further. Based on existing partnerships with foreign manufacturers, the first international deliveries of the Sputnik V vaccine will be made in January 2021. Those customers, who have recently submitted their requests, will be able to receive the first batches starting from March 2021.

Are you planning to be a part of COVAX? How do you think it will benefit equitable distribution of the vaccine?
It is clear that no single vaccine can be sufficient for the world. We need to have several solutions at our disposal and countries need to secure access to a
portfolio of vaccines to achieve maximum results.

The collaborative approach of having diverse vaccine options is the step in the right direction to stop the spread of the coronavirus. We are open to partnerships and are willing to cooperate with all the states and global entities. For this reason, we would want Sputnik V to be part of the COVAX portfolio of vaccines. The world is need of Covid-19 vaccines and we should all work together to provide them safely, efficiently and to all. We definitely aim to join the COVAX initiative because we see it as crucial in delivering the vaccines
globally, including to countries that need them most. We are in constant contact with GAVI, CEPI and WHO and are preparing for the application for COVAX through UNICEF.

How will Russia’s application for pre-qualification and emergency use listing help in getting early licensure for Sputnik V?
First of all, we are extremely grateful to the World Health Organisation for its cooperation and we are looking forward to the successful conclusion of the process of pre-qualification at all the crucial stages. We are going through the approval process and are in constant communication with the WHO on our application. Pre-qualification will make the vaccine qualify for worldwide access as we believe we will be able to abide by the set standards of safety, quality and efficacy. Sputnik V will be included in the list of medicines that will be used by global procurement agencies and nations to manage bulk buying of medicines.

What challenges do you foresee in the development of Sputnik V in the coming months?

The main focus in the coming months will be the successful completion of phase III clinical trial, followed by the publication of their results. We are confident in Sputnik V as, unlike some other vaccines in development, it is based on an already well-proven technology, but there are still many global regulatory hurdles that would need to be overcome for it to reach consumers. Another issue at hand is how fast production can be scaled and whether it will be fast enough to minimise the virus’s impact. The main task is the launch of large bioreactors in Russia to boost production; this is already happening and we are on the way to meet our year-end target capacity of 5-7 million doses/month.

At what stage of development is Russia’s second candidate for Covid-19 vaccine?
Russia approved its second vaccine, EpiVacCorona, in October. The antigens-based vaccine is being developed by The Vektor Institute in Novosibirsk, Siberia. It is now in phase III of clinical trials.

Unlike Sputnik V, this vaccine contains synthetic peptide antigens, fragments extracted from the virus, that provoke an immune reaction to Covid-19 and stimulate immunity development.