By Charles F. Moreira, Editor
As mentioned in our earlier article, China-based biotechnology companies are amongst the first worldwide to have begun phase III clinical trials of their domestically developed COVID-19 vaccines, with China National Biotec Group (CNBG) and Sinovac expecting their vaccines to be ready for public use by the end of this year.
Also, on 11 August, Russian President Vladimir Putin announced that his country had registered the world’s first Covid-19 vaccine Sputnik V after it had successfully completed phase I and II testing. It will go on to undergo phase III clinical trials launched on 26 August involving 40,000 volunteers before releasing it to the general public next year. Meanwhile, the vaccine candidate will be distributed to selected groups such as medical personnel and teachers.
Critics regard this as a ‘shortcut’ by Russia. However, this is understandable considering the urgency of the situation where that country has over on million COVID-19 cases at time of writing, or the fourth highest number worldwide after the United States, India and Brazil.
Also, a report by Center for Infectious Disease Research and Policy of University of Minnesota revealed the COVID-19 pandemic will likely last 18 to 24 months, while 60 to 70 percent of the population may need to achieve herd immunity for halting the pandemic, and a vaccine is believed to be one of the most imperative key to stop the spread.
Whilst the above developments are welcomed by many people and countries which have been anxiously waiting for a vaccine which can potentially help end the COVID-19 pandemic which has infected close to 30 million people worldwide and caused close to one million deaths, whilst the lockdowns and travel restrictions have had serious economic consequences.
Despite that, there are others, especially in the west who question the efficacy and safety of the above vaccines, some for valid reasons and others for political or commercial agendas.
China supports the COVID-19 Vaccines Global Access (COVAX), one of three pillars of the Access to COVID-19 Tools (ACT) Accelerator, which was launched in April by the World Health Organization (WHO), the European Commission and France in response to this pandemic, however the United States refused to join COVAX’s international efforts to develop a COVID-19 vaccine.
However, some western media have accused China of having ‘stolen U.S. research data in COVID-19 vaccines’, whilst some Western countries consistently alleging that China’s vaccine research is part of a ‘global influence campaign’.
Faced with such hostility, China is concerned that any safety problems with its vaccines. especially in other countries, could lead to legal biosafety disputes.
“We have to be very clear that if Chinese vaccines break any law or restrictions in host countries, and vice versa, whether Chinese home-grown technology can be well protected from infringement by local enterprises,” said Xu Xinming, a Beijing-based lawyer specializing in intellectual property rights, told the Global Times.
“In bilateral cooperation on vaccines, ways of resolving disputes over bio-safety (such as coping with potential side effects) should be specified in the contract. Failing to do so risk the vaccines being politicised”, Xu warned.
However, Xu urges enterprises to take the lead in cooperation and protect self-interests using international rules, whereas governmental institutes or diplomatic tools should only be used to assist countries in resolving disputes.
There also are economic risks for China’s vaccine producers, since China has pledged to offer the successful COVID-19 vaccine to at least 10 developing countries, most of which of which are low-income countries, which raises concerns that the high R&D costs involved cannot be recouped.
Guns trained on Sputnik V
On 14 September, 15 scientists, mostly from Italy, as well as from Sweden, Britain, the United States and Japan had signed a formal letter to the internationally respected British medical journal, The Lancet, challenging the accuracy of early data on Russia’s COVID-19 vaccine. The 15 have expertise in virology, immunology, pharmaceutical development, research integrity and statistical analysis.
Results of Sputnik 5’s phase I and II clinical trials by Moscow’s Gamaleya Institute which developed Sputnik V .were published in The Lancet on 4 September after having undergone a thorough peer review process. The results show no serious adverse events under any of the criteria, with all participants in the Sputnik V trials having generated a stable humoral and cellular immune response.
However, the 15 said they found patterns in the Phase I and II trial data, which was peer-reviewed in the journal, to appear ‘highly unlikely’, with multiple participants reporting identical antibody levels.
Earlier, the phase one clinical trial results of China’s Ad5-nCoV adenovirus candidate vaccine was published in the Lancet on 22 May, showing that all 108 volunteer participants had produced antibodies against the novel coronavirus after vaccination.
This is the world’s first results of human trials released on COVID-19 vaccines and they demonstrate that the vaccine is able to introduce a dual immune response in the recipient, namely humoral immunity and cell immunity.
Meanwhile, according to an article in the Australian publication The Conversation on 5 September, argues that there is ‘nothing novel’ about adenovirus-based vaccines such as Sputnik V, that developed by China’s CanSino Biologicals, Oxford University and Johnson and Johnson, since they are based upon the common cold viruses called Ad5 and Ad26.
Such neutered adenoviruses cannot grow in the body and only function to deliver the genetic code of one of the novel coronavirus proteins, called the spike proteins, into human cells after vaccination, so as to stimulate the body’s immune system to develop defences against the SARS-CoV-2 coronavirus which causes COVID-19 in humans, hopefully for many years in the future.
“So it’s safe, at least in healthy people aged 18 to 60, but does it work – does it protect against COVID-19?”, The Conversation’s article asks.
The article accepts that the Russian group showed that their vaccine induces high levels of antibodies that can bind to the spike protein but questions the level of antibodies that are functional and whether the antibodies can prevent or neutralise, infection of a virus into a cell.
“The levels of neutralising antibodies were quite low in this study, compared with other published vaccine trials. So too were the T cell responses (the other arm of the immune system’s adaptive response)”, the article contends.
“One interpretation of this is that these vaccines do not induce good neutralising protection. Alternatively, the methods used to measure these immune responses may not have been optimal. In the absence of international reference standards, we can’t tell if this vaccine is better or worse compared with others.
“Crucially, as with other COVID-19 vaccine clinical trials, we don’t know if that level of neutralisation is enough to protect from infection and how long these antibodies remain in the blood. The publication shows responses only up to one month after immunisation. The ultimate question of whether these vaccinated people are protected against COVID-19 was not a focus of this paper”.
The Conversation article goes on to argue that all vaccines need to be tested in large numbers of people, of different ages and ethnicities, in phase three clinical trials, so as to gain a high-level of confidence that the vaccines protects against infection and . Phase three trials are necessary to gain a high level of confidence that the vaccine protects against infection and also unveil any rare side effects which may not be evident amongst a small group of healthy volunteers.
“Unfortunately, the Sputnik moniker highlights the politicisation of earnest scientific and medical efforts to develop vaccines against COVID-19. This ‘vaccine nationalism’ is a source of much concern for everyone in the vaccine field who understands the power of vaccines to eliminate disease, but only when used with the acceptance of the population”, The Conversation article concludes.
Russia fights back
Meanwhile, Kirill Dmitriev, Chief Executive Officer of the Russian Direct Investment Fund (RDIF) rebuts the critics of Sputnik V in an article in Russia Today on 7 September.
The RDIF is a sovereign wealth fund established in 2011 to make strategic investments in Russia and abroad and now funds the development the most promising COVID-19 testing systems, drugs and vaccines and it supports the development of Sputnik V by the Gamaleya Center.
On the argument by critics that 76 participants in Phase 1 and 2 clinical trains of Sputnik V is too small to be reliable compared to the 1,077 participants in AstraZeneca’s Phase I and 2 trials, Dimitriev counters:-
“On the surface the Sputnik V trial with 76 participants seems smaller in size compared to 1,077 people that, for example, AstraZeneca had in its Phase 1-2 studies. However, the design of the Sputnik V trial was much more efficient and based on better assumptions”.
“AstraZeneca ran its trial from the beginning with a one-shot model but that was a false assumption since only a two-shot model can provide a long lasting immunity as AstraZeneca conceded following the trials.
“As a result of wrong initial assumptions, AstraZeneca tested the two-shot model only on 10 people out of 1,077. Overall, the number of people who received two injections in the Sputnik V trial exceeded the similar number in AstraZeneca trial by 4 times. Most media missed this point”, Dimitriev contends.
Besides the ongoing Phase III clinical trials involving 40,000 persons in Russia, Phase III trials of Sputnik V will begin in Saudi Arabia, United Arab Emirates (UAE), the Philippines, India and Brazil this month (September) with will begin this month, with the preliminary results being published in October-November 2020.
Russia had gone ahead and registered Sputnik V for emergency use because of the very positive results of its Phase I an II trials and because the human adenoviral vector-based delivery platform has proven to the the safest delivery platform over decades.
“The scientists provided convincing data on safety of use of human adenoviral vaccines and medicines worldwide based on studies since 1953. According to records, more than 10 mlllion U.S. military personnel have received human adenoviral vaccines since 1971. A cancer treatment, Gendicine, based on human adenoviral vectors has been administered to more than 30,000 people in China in the course of 15 years. Clinical trials of vaccines based on human adenoviral vector technology using the same vectors as Sputnik V, have already involved more than 25,000 people worldwide. Since 2015 more than 3,000 people were administered human adenoviral vector-based vaccines against Ebola fever and Middle East Respiratory Syndrome (MERS) created in the Gamaleya Center”, said Dimitriev.
“So Russia registered the vaccine because it had a, previously approved, safe and efficient human adenovirus delivery platform for other illnesses. Since the registration of Sputnik V in Russia, other countries also announced plans to follow the Russian approach for emergency use registration of their vaccines.
“Sinovac Biotech’s vaccine received a similar approval in China. The government of the United Kingdom and the head of the US Food and Drug Administration (FDA) Stephen Hahn have signalled the potential for fast-track registration for British and American vaccine makers, respectively, despite their earlier reservations”, he added.
No to ‘vaccine nationalism’
As the vaccine race intensifies alongside the progress in vaccine development worldwide, Chinese analysts warned against ‘vaccine nationalism’ and have called for international cooperation against the pandemic.
World Health Organisation (WHO) Director-General Tedros Adhanom Ghebreyesus told a briefing that vaccine nationalism will prolong the problem, not shorten it, adding that using vaccines effectively across the world is “a global public good” and it is in the “the national interest of each and every country.”
China has promised as early as May to make its COVID-19 vaccines, when available, a global public good, which will be China’s contribution to ensuring vaccine accessibility and affordability in developing countries, whilst its also pooling efforts in international cooperation to secure a fair distribution of COVID-19 vaccines without geopolitical boundaries.
Altogether 172 economies including China are engaged in discussions to potentially participate in COVAX, which is looking to deliver two billion doses of safe, effective vaccines that have passed regulatory approval and/or WHO pre-qualification by the end of 2021.