The World's First New Coronavirus Vaccine was Approved, and the Vaccine Safety Risk Caused an Uproar

An immunologist, M, who did not want to be named, said : By bypassing the Phase III clinical trial and directly applying it on a large scale, there may be certain safety risks and hidden dangers, especially adverse reactions and effectiveness issues. Therefore, I hope that countries will not be stimulated by Russia. We need to remain rational and cautious. Of course, if the Russian vaccine is successful, it can reduce the pressure on countries' imported new coronavirus vaccines from Russia; it can also provide experience for other country's vaccine development.

WHO Hopes to Strictly Review the Safety of Vaccines

Recently, a piece of news made a sensation in the vaccine circle.

On August 11, local time, Russian President Putin announced at a government meeting that Russia has become the first country in the world to approve the new coronavirus vaccine. After two months of human clinical trials, the country's first new coronavirus vaccine has been registered in Russia.

This means that in the global new coronavirus vaccine research and development competition, Russia, the dark horse, broke the siege, surpassed the Chinese, British and American teams, and finally took the lead.

Putin hopes that the vaccine will be mass-produced as soon as possible. He also revealed that one of his daughters also participated in a clinical trial and that the body has high levels of antibodies after receiving the vaccine.

Source: BBC

However, as soon as the news was announced, it caused an uproar in the scientific community. This vaccine has passed the Phase III clinical trial and directly registered, causing widespread doubt and condemnation. A spokesperson for the World Health Organization (WHO) warned that vaccine safety should not be compromised in the fight against the new coronavirus.

So, is this Russian vaccine that does not follow the routines, is it reliable?

In the 2-Month Human Test, Only 76 People were Tested

The development of conventional vaccines is long and expensive, requiring a cycle of several to ten years. However, in the face of the major public crisis of the new coronavirus epidemic, all research and development are accelerated and shortened.

The WHO hopes that the development time of the new coronavirus vaccine will be as short as possible within 12 to 18 months. But Russia’s vaccine, developed by the Gamaleya Research Institute of Epidemiology and Microbiology, has been approved in less than two months in human trials.

On the clinicaltrials website in the United States, the vaccine has a clinical phase II trial record, which mainly tests the safety of the vaccine.

The experiment designed two groups of subjects, each with 38 subjects, a total of 76 subjects. Several reports showed that these participants were isolated in two different hospitals in Moscow, but the specific results of the clinical trials were not announced.

A vaccine expert said, 'For the global epidemic prevention and control, the registration and listing of the new coronavirus vaccine in a large country like Russia is undoubtedly very good news. However, scientifically speaking, there is really no relevant news before. The effectiveness and safety of the vaccine need more data to support.'

Compared with inactivated and attenuated vaccines, adenovirus vectors are a new type of vaccine technology. Scientists use 'castrated' or 'modified' harmless adenovirus as a carrier to carry and transfer the S-Protein gene of the new coronavirus, thereby stimulating the body's immunity.

In addition to Russia, vaccines jointly developed by China's Sino Biological and Military Academy, Oxford University and AstraZeneca are also adenovirus vector vaccines.

The difference between the three is that China and Russia use human adenovirus, while the UK is based on chimpanzee adenovirus. There is no essential difference between the two.

Adenovirus vector vaccines are relatively safe and efficient, but they may not be effective. There is a problem of 'pre-existing immunity', that is, most people have been infected with adenovirus during their growth, and there may be antibodies that can neutralize the adenovirus vector in their bodies. This may attack the vector and reduce the effectiveness of the vaccine. It is believed that the pre-existing immunity of adenovirus vaccines can be solved by multiple vaccination to make up for the lack of effect.

Is it Scientific or Political to Bypass Phase III Clinical Trials?

There are three phases of vaccine clinical trials, of which phase III clinical trials are crucial.

Generally speaking, only through phase III clinical trials can vaccines be successfully approved for marketing.

Phase III clinical trials are designed to test whether the vaccine is effective against viral infections and potential side effects. It takes the longest time and has the largest sample size. It needs to enroll thousands or even tens of thousands of people. Generally, observe an epidemic cycle to determine the vaccine's protection rate for susceptible people.

According to incomplete statistics from WHO, as of August 10, there were 167 COVID-19 vaccine projects under research worldwide, 28 of which have entered the clinical trial stage, while only 6 teams have entered phase III clinical trials. China accounted for three seats, Britain, America and Germany each have one seat.

Source: WHO, DRAFT landscape of COVID-19 candidate vaccines

Before the sudden emergence of the Russian team, the leaders in vaccine research and development were fighting for the speed and results of Phase III clinical trials.

For example, In China, Sino Biotech and Kexing Zhongwei have been approved to conduct phase III clinical trials of the new coronavirus vaccine in three overseas countries. Sino Bio will carry out trials in the UAE. Kexing Zhongwei will carry out phase III trials in Brazil and Bangladesh respectively. The former is expected to involve 9,000 people and the latter is expected to recruit 4,200 volunteers.

In addition, Oxford University and AstraZeneca Phase III clinical trials are expected to recruit 10,000 volunteers in the UK and 30,000 in the United States. On June 2, the Brazilian Health Administration approved Oxford University’s request to recruit 2,000 volunteers in Brazil to participate in the Phase III trial.

Although President Putin has repeatedly emphasized that the Russian vaccine has passed all necessary inspections and is quite effective, the vaccine has been widely condemned by the scientific community due to the lack of phase III clinical trial results.

Russian scientists commented on this. Source: "Science" magazine (Science)

'Russia's rapid development of vaccines arouses people's anger about its safety', 'Nature'

The WHO said it would pay attention to the development of the Russian new coronavirus vaccine and hope to review the safety of the vaccine.

'Science' magazine commented that this was a shocking and confusing move.

'This is ridiculous, and I am ashamed of our country." Svetlana Zavidova, a lawyer and chairman of the Association of Clinical Research Organizations in Russia, told Science. This scientist with more than 20 years of clinical trial experience appealed to the Russian Ministry of Health yesterday to postpone vaccine registration until the clinical trial is completed.

She wrote on behalf of the clinical research team: Accelerating vaccine registration will no longer make Russia a leader in this competition. It will only expose the end users of the vaccine, that is, citizens of the Russian country, to unnecessary risks.

Other vaccine expert in Moscow believes that Russia’s vaccine has passed Phase III clinical trials. On the one hand, this may be related to the country’s different approval procedures and routines. On the other hand, the political significance of the news (first registration, large orders, and social confidence enhancement, etc.) is greater than actual scientific significance.

In fact, emergency approval of similar vaccines is not uncommon.

For example, the U.S. Food and Drug Administration (FDA) can approve the use of drugs through emergency use authorization before the efficacy trials are completed.

Zavidova told the media that Russia’s certification process is similar to the FDA’s emergency use, but the FDA has an independent advisory committee mainly composed of academics that regularly reviews vaccine approval applications.

Regarding the meaning of national registration, some Chinese vaccine experts told the media that after registration, the new coronavirus vaccine can be produced and legally and normally vaccinated. In fact, it may be vaccinated for high-risk groups first, but not necessarily directly on the market.

It can be seen from the certificate issued by the Russian State Drug Registration Agency for the vaccine that the vaccine is only allowed to circulate in the private sector before January 1, 2021. A spokesperson for the Russian Ministry of Health said the certificate allows the vaccine to be given to 'a small number of vulnerable citizens', including medical staff and the elderly.

Coincidentally, special approval of vaccines also exists in China.

In the face of doubts from the outside world, Kirill Dmitriev, president of the Russian Direct Investment Fund, told the Russian news agency TASS that the vaccine phase III clinical trial will be launched 12 days after registration and is planned to be carried out in the UAE, Saudi Arabia and the Philippines. The data of each phase of the test will be announced as soon as it is obtained.

According to 'Science' magazine, the Russian vaccine will be produced by Binnopharm in Zelenograd. The company can produce 1.5 million doses of the product each year and hopes to expand its production capacity.

According to the Gamalian Institute, Russia has received orders for 1 billion doses of vaccine from 20 countries and plans to produce the vaccine in Brazil, India, South Korea, Saudi Arabia and Cuba.

In the face of the New Coronavirus Pandemic, is it Safe or Effective?

Putin said that one of his daughters had high levels of antibodies after being vaccinated.

However, high levels of antibodies do not mean that the vaccine is effective.

In fact, as a foreign antigen, vaccines will cause the body to produce antibodies and immune responses after being injected into the human body. However, for a successful preventive vaccine, it is necessary for the body to react quickly to the same antigen within a long period of time.

After the vaccine is injected, the higher the titer and the longer the duration, the more long-term protection can be provided.

The protection rate of the vaccine has become an important indicator of the success of phase III clinical trials. In the face of the epidemic, the restrictions on these effectiveness indicators have been relaxed.

On June 30, the FDA issued the 'Industry Guidelines: Development and Approval of COVID-19 Preventive Vaccine' document by the Center for Biological Products Evaluation and Research, which requires that the protective efficacy of the marketed vaccine is at least 50% higher than that of placebo.

But usually a vaccine has a protection rate of over 80% before it is qualified. Among the active vaccines, except for the low protection rate of influenza vaccine (about 70%), other vaccines exceed 80%, measles vaccine exceeds 90%, and rabies vaccine is even higher.

In other words, the FDA's requirements for the protection rate of new coronavirus vaccines in emergency situations are lower than those of general vaccines. But this data needs to be provided by Phase III clinical trials.

Since the Russian vaccine team has not released relevant data at present, its safety and effectiveness are still unknown.

Taulina is more optimistic. He told the medical community: 'Russia’s skipping of Phase III trials will reduce the confidence of the vaccine’s effectiveness. But in the current state of emergency, if safety can be ensured, even if the assurance of effectiveness is lowered, I seem to be acceptable.'

According to statistics from Johns Hopkins University, as of 20 o'clock on August 12, Russia has more than 900,000 new coronavirus pneumonia cases, of which 15,231 people have died.

Reference 

1.WHO cautions Russia on COVID-19 vaccine.https://www.aa.com.tr/en/asia-pacific/who-cautions-russia-on-covid-19-vaccine/1938509

2. Russia’s approval of a COVID-19 vaccine is less than meets the press release.

https://www.sciencemag.org/news/2020/08/russia-s-approval-covid-19-vaccine-less-meets-press-release

4. Putin announced that Russia has registered the world's first new crown vaccine. WHO: Will evaluate its safety. https://finance.sina.com.cn/world/gjcj/2020-08-12/doc-iivhvpwy0522480.shtml

5. New crown vaccine special report: inactivated vaccines are leading the world, and recombinant protein vaccines have great potential. Shanghai Securities. http://pdf.dfcfw.com/pdf/H3_AP202007101390778875_1.pdf