While major pharmaceutical companies around the world are hoping to introduce a vaccine by the end of the year, Russia announced in August the launch of Sputnik V, its home-made adenovirus-based candidate vaccine against COVID-19, for citizens. India has also decided to take the Russian vaccine after clinical trials with Indians.
Lalit Kant, an infectious disease epidemiologist and former chief of epidemiology and communicable diseases at the Indian Council for Medical Research (ICMR), spoke about why phase III clinical trials are important for the Russian vaccine, the adenovirus vector vehicle of the vaccine. , advantages for India and the way forward. Edited excerpts from an interview:
What do you think about the safety of the Russian covid-19 Sputnik V vaccine?
This is the first vaccine against Covid-19 approved worldwide. The vaccine is reportedly already available to the public in Moscow. Scientists and health agencies have warned against euphoria as the vaccine has been approved without the results of the phase I / II trial being made public or the phase III trial being conducted. Phase III trials are essential to understand the safety and efficacy of the vaccine.
Russia’s level of confidence can be measured by the fact that they are not seeking full compensation for legal risks from countries that have shown interest in using their vaccine. This is very different from what other manufacturers are looking for: full compensation, meaning full protection against future liability claims arising from adverse reactions with the countries where they have signed supply agreements. Whether the vaccine would turn out to be a Sputnik moment or Russian roulette, the results of Phase III will tell.
Please explain the adenovirus vectors on which the Russian vaccine is based.
The Russian vaccine uses adenovirus (which commonly causes the common cold in children) as a vehicle to transport the adenovirus vector that carries the S gene encoding the ‘spike protein’ of SARS CoV2 into the human body. The adenovirus enters cells and discharges the genetic load. It uses a prime booster strategy, that is, the vaccine is given in two doses 21 days apart.
Research on the use of adenoviruses to transport foreign genetic material has been being refined since the 1980s. The advantage of using adenovirus vectors is that the vector has surface proteins that help facilitate delivery of the SARS-CoV- nucleic acid. 2 to the host cell, which then transcribes it to become viral antigens. Adenoviruses have been isolated from humans, apes (monkeys), and birds. Human adenoviruses have more than 50 serotypes and Ad5 is the most common.
Since adenoviruses are present throughout the world and almost all of us would have been exposed to it during our childhood, we all have immunity. This pre-existing immunity has been one of the main reasons that adenoviral platforms have had very limited success so far. The only successful application of this strategy has resulted in the development and approval of a rabies vaccine for use in animals. Although great efforts have been made to develop a vaccine against HIV, malaria, tuberculosis, Ebola and the Zika virus. Several approaches have been used to overcome the problem of pre-existing immunity, such as using isolated adenoviruses from chimpanzees for which humans may not have immunity, administering the vaccine in two doses, each using a different serotype of adenovirus, and one one of them could be common as Ad5 and the other rare serotype as Ad26 and Ad35, or use a totally rare serotype.
Adenovirus has also been genetically altered and some of its own genes have been deleted and therefore it cannot replicate and thus minimize reactions with pre-existing immunity. Several companies are using the adenoviral platform for Covid-19 vaccines and some of them are in an advanced stage of clinical development, for example.
AstraZeneca from the UK uses chimpanzee adenovirus, the Johnson and Johnson vaccine from the USA is based on Ad26 and China’s CanSino Biologics is using Ad5 as a vector. The Russian vaccine uses serotypes Ad5 and Ad26 for its preparation and boost strategy. These vaccines aim to stimulate both arms of the immune system, the antibody and T-cell responses, so that they attack the virus as it circulates in the body and also attack cells infected by SARS-CoV-2.
Many countries, including India, are considering the emergency authorization of covid vaccines. Why do you think phase III clinical trials are important for any country?
For a vaccine to be prequalified for global use by the World Health Organization (WHO), data for all three phases of the clinical trial (Phase I-III) are required for review, although each country may have its own approval criteria in his country. . At the time the Russian vaccine was approved by its national authorities, it had data for Phase I / II and none had been published. Since its publication in The Lancet, scientists have been raising the red flag by observing ‘strange duplicate patterns in the data, between different groups looking at different groups’ and have called for a new review of the raw data.
Since its approval in August, phase III trials of the Sputnik V vaccine have begun in Russia, there are reports that approximately 14% of the 300 volunteers who received the vaccine have had self-limited mild side effects (weakness, muscle pain and increased temperature). and chills). The trial is in 40,000 volunteers and results are expected by the end of October 2020.
The immune response observed in Phase I / II of the Russian vaccine trial may not be proportional to the degree of protection being studied in Phase III alone.
India will also conduct clinical trials of the Sputnik vaccine in its population. What is your opinion on the side effects of the Russian vaccine during the clinical trials already conducted?
If for any reason Sputnik does not work or results in some kind of unforeseen adverse event in Phase III that could affect public perception of the vaccine process. An inefficient product could make the pandemic worse, as those who receive the vaccine may fail to take precautions. Confidence can be affected by a vaccine that was approved and later shown to be harmful. Safety is of the utmost importance as the vaccine is administered to healthy people and must be balanced against the risk of infection. A vaccine that reduces the severity of the disease but does not prevent infection can make things worse.
What are the advantages of the Russian vaccine for India?
One of the formulations of the Russian vaccine is lyophilized. In my opinion, this is the biggest advantage it offers. The benefits of lyophilized products include lower cold storage requirements, lower shipping costs, simplified product use, and longer shelf life. This formulation could be used within the existing refrigerated cold chain in India, the stability of the product would maximize the reach in remote areas, which will help universal and equitable coverage. Brazil, Cuba, the Philippines, the United Arab Emirates, and Saudi Arabia have agreed to conduct a phase III clinical trial.
On September 16, Dr. Reddy’s Laboratory, Hyderabad announced that it had signed an agreement with the Russian Direct Investment Fund (RDIF) to conduct Phase III testing of the Sputnik vaccine. Russia is reported to have submitted complete data on the safety and immunogenicity / efficacy of vaccines to India. If all goes well, this could happen before the end of 2020. About 100 million doses will be available for use in the Indian population soon after. If Phase III trials begin in September, it would be the first vaccine to enter Phase III in India and could become the first vaccine to be licensed for use. If the candidate vaccine is quickly tracked and given an emergency clearance, it may well be available sooner.
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