No test results to back up Russia’s coronavirus vaccine but Russia will mass produce anyway

No test results to back up Russia’s coronavirus vaccine but Russia will mass produce anyway
Russia claims it has developed an effective vaccine against the coronavirus (COVID-19) but researchers have not shared any of the efficacy results from the early trials
By Ben Aris in Berlin August 13, 2020

Russia has registered the world’s first vaccine against the coronavirus (COVID-19) and is already launching mass production of the drug, President Vladimir Putin announced during a government meeting on August 11.

However, medical testing of the vaccine is not finished and the Kremlin has been accused of jumping the gun to score political points. bne IntelliNews approached the Russian Direct Investment Fund (RDIF), Russia’s sovereign wealth fund that has championed the development of the drug, for more information.

We received details of the “vectors” being used to deliver the DNA at the heart of the treatment but a request to share the efficacy results from the first two phases of testing were met with silence.

On August 10, the non-profit Association of Clinical Research Organisations (AOKI) called on Russia’s Health Ministry to postpone the registration of the vaccine. In an open letter, AOKI emphasised that the Gamaleya Institute, which is developing the vaccine, had yet to complete any trials involving “even hundreds of people” and said that mass production of the drug had yet to be developed, reports Meduza.

In response both Russia’s federal healthcare watchdog, Roszdravnadzor, and the Health Ministry’s chief epidemiologist, opposed delaying the registration process. Rosdravnadzor’s Deputy Head Valentina Kosenko told RBK that the vaccine had been tested on several hundred volunteers without any adverse side-effects. She also added that the third phase of the vaccine trials would involve several thousand volunteers, Meduza reports.

Similarly, the Health Ministry’s chief epidemiologist, Nikolai Briko, insisted that he saw no reason to “put obstacles” in the way of registering the Gamaleya Institute’s coronavirus vaccine, adding that accelerating the registration process made sense in the context of the ongoing COVID-19 pandemic. “It [the vaccine] has shown that it’s safe, it’s continued effectiveness will be studied,” Briko said.

The reticence to share efficacy numbers may also be due to the amount of money that is on the table: the RDIF reportedly believes it can capture up to a quarter of the estimated $75bn market for an effective vaccine. And Russia’s sovereign wealth fund is, at the end of the day, a fund. Its boss Kirill Dmitriev cut his teeth as a private equity investor, who ran Icon Private Equity, the private equity vehicle for Russia’s richest man Suleyman Kerimov and Ukrainian oligarch Viktor Pinchuk, and was also the head of Russia’s Private Equity Association, before being appointed the head of the RDIF.

According to the Russian president, the vaccine is effective, builds stable immunity, and has passed all of the necessary tests in the first two phases of testing. However, the crucial phase III tests have yet to be conducted. Usually a new drug has to pass all three phases before it is registered and released to the public. Russia has skipped over the last stage and is starting mass production and inoculations in parallel with the phase III testing.

Putin is so confident of the vaccine’s safety that he allowed one of his two daughters to be inoculated. “On the second day her temperature went up to 38C, but after that it went back to normal. That’s all,” the president said on nationwide TV.

The announcement has been met with a storm of derision which is grounded in the legacy “exploding TVs” image Russia has for R&D. Observers cannot believe that a Russian pharmacologist could have got the jump on the West’s world-class drug manufacturers and Western governments that are pouring billions of dollars into research.

But by releasing no information at all on the results of the Phase I & II tests the Kremlin has opened itself up to the scepticism.

Research and development

Russia’s scientific reputation is spotty. It was the first country to put a man into space, which amazingly it did in the context of a brutally oppressive centrally planned totalitarian state. There is no question of its prowess in the theoretical sciences either. Dmitry Mendeleev discovered the periodic table and Nikolai Lobachevsky’s non-Euclidean geometry is the mathematical system Albert Einstein used as the basis of his relativity theory, to name two examples.

In terms of more hands-on applications of science, Russia’s aviation, radar, weapons and nuclear technology are all world-class. But it is not famous for pharmacology and has little to show in this field.

That has changed a bit in recent years. Virological research is centred on the State Research Centre of Virology and Biotechnology in Koltsovo in the Novosibirsk Oblast, known simply as the Vector Institute.

It is one of two official repositories for the now-eradicated smallpox virus, and was part of the system of laboratories known as the Biopreparat in the Soviet-era. Recently the facility has been upgraded and security improved. The facility has, at least in Soviet times, been a nexus for biological warfare research but since independence has turned to civilian projects. The Vector institute headed up Russia’s early response to the coronavirus (COVID-19) epidemic and was the centre of testing at the start of the outbreak.

However, the Gamaleya Research Institute, an epidemiological centre running one of the vaccine trials, is conducting research on the new coronavirus vaccine.

Gamaleya has an expertise in adenoviral-based vectors, the RDIF told bne IntelliNews. A vector is the cell that is used to transport the vaccine DNA into the host cells that provoke the production of anti-bodies that give the host an immunity to infection.

And this experience is actually quiet extensive, as Gamaleya has worked on a vaccine against Ebola and the Middle East Respiratory Syndrome (MERS), which belongs to the same family as COVID-19 and kills in a similar way.

Research into Ebola got a big boost when there was a deadly breakout of the Ebola virus in Guinea that affected a bauxite deposit belonging to aluminium producer Rusal and owned by oligarch Oleg Deripaska. The virus infected a total of 29,000 people and killed 11,310 people – the largest and most lethal outbreak of the virus since it was discovered. The WHO classed the outbreak as a global threat.

In less than two months Deripaska had funded and built a $10mn epidemiological and microbiological diagnostic centre in Guinea’s Kindia Province that is still there today and funded research in Russia too. Russian doctors were flown in to treat patients and thanks in part to Rusal’s efforts the 2014 outbreak was halted, the contagion was contained within the region, and a pandemic was avoided.

Thanks to this research the delivery system of using adenoviral-based vectors seems to be thoroughly researched and effective. What the Gamaleya institute has produced is a neat package into which different anti-viral DNA can easily been placed and effectively delivered to a host.

“Human adenoviruses are considered as some of the easiest to engineer in this way and therefore they have become very popular as vectors,” the RDIF spokesperson said.

“The efficacy and safety of these vaccines has been validated through years of testing. Nowadays, this is the safest mechanism for introducing the genetic code of the virus spike into the human body, and it has been thoroughly studied not only in Russia but also abroad,” a spokesperson for the RDIF said in comments emailed to bne IntelliNews.

However, that says nothing about the effects of the DNA that constitute the meat and potatoes of the vaccine, which is new.

The key element is a gene from adenovirus, which causes the infection, is removed and a gene with the code of a protein from coronavirus virus is inserted in its place.

“After the start of the COVID-19 pandemic Russian researchers extracted a fragment of genetic material from novel coronavirus SARS-COV-2 [COVID-19’s official name], which codes information about the structure of the spike S-protein, which forms the virus’ “crown” and is responsible for connection with human cells. They inserted it into a familiar adenovirus vector for delivery into a human cell, creating the world’s first COVID-19 vaccine,” the RDIF said.

 

“This inserted element is safe for the body but still helps the immune system to react and produce anti-bodies, which protect us from the infection,” the spokesperson explained.

On paper is should work; in practice things can go wrong.

For example, the shape of the molecule is important. Just how that “crown” latches on to a host's cell makes a difference, but it is hard to predict what differences in the shape will do, as different shaped molecules can be chemically identical.

Famously in the 1950s and 1960 doctors developed thalidomide, a drug proscribed to pregnant women in 46 countries, which resulted in the "biggest man‐made medical disaster ever." 

In that case the drug actually worked, except many molecules have two chemically identical versions: one that spirals clockwise and a mirror image that spirals anti-clockwise, for example. In the case of thalidomide the clockwise version did what it was supposed to, but the mirror image produced horrific deformities in new-born children. And the chemical process used to mass-produce the drug produced equal parts of both versions.

Mass production

However, no one within the Russian effort has shared any of the efficacy results from the preliminary trials with the general public, presumably so far so good.

And it is not given that the vaccine will give its recipients immunity, but could just improve their odds of surviving unscathed if they are infected. It has proved particularly difficult to develop vaccines for the other viruses in the coronavirus family: after years of research there is still no effective virus against SARS or MERS, both of which are similar to COVID-19.

Nevertheless, Russia is pushing ahead with the mass-production of the vaccine that will be put into general circulation in January next year on a voluntary basis. The Gamaleya Institute’s head, Alexander Ginzburg, said that the vaccine will be brought into circulation in Russia’s regions after the start of the third phase of trials in Moscow, which they are prepared to start “as soon as the money comes in.”

Russian Health Minister Mikhail Murashko said that the vaccine will be produced by the Gamaleya Institute, as well as the Zelenograd-based company, Binnopharm. Other enterprises will begin producing the vaccine at a later date.

Deputy Prime Minister Tatyana Golikova, who oversees the whole social sphere, said that Russia could begin vaccinating healthcare workers against the coronavirus at the end of August or September this year. The Health Ministry hopes that the vaccine will help maintain long-term immunity to the coronavirus, possibly for up to two years.

That is another problem: viruses are, by definition, highly mutable, and so there is no guarantee that a vaccine that works this year will still work next year.

 

 

 

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