Antalya, TURKEY - August 11, 2020. The Covid-19 coronavirus vaccine produced in Russia named Sputnik-V. Russia's coronavirus vaccine concept

Image credit: Yalç?n Sonat / 123rf

The world has yearned for a vaccine against the novel coronavirus that causes COVID-19 since the pandemic began. However the recent announcement of Russia’s coronavirus vaccine has been met with scepticism – justly or unjustly.

COVID-19 – the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), or simply coronavirus – has disrupted virtually every facet of the global economy and of our societies. It has resulted in untold human anguish, as hundreds of thousands of lives have been lost and many remain in intensive care.

The hunt for treatments for COVID-19 and, eventually, a coronavirus vaccine has been underway since the pandemic’s early stages. There have been indicators of progress. For example, the vaccine ChAdOx1 nCoV-19, developed by the University of Oxford in the United Kingdom, enjoyed research findings BBC News described as “hugely promising” following trials involving 1,077 people. Meanwhile, research indicated that the corticosteroid medication dexamethasone reduces the risk of mortality among COVID-19 patients.

However, our understanding of COVID-19 and the novel coronavirus that causes it is evolving. As such, all breakthroughs – no matter how highly-touted in the press – must be met with caution. In the case of ChAdOx1 nCoV-19, the BBC News report also emphasised that “it is still too soon to know if this is enough to offer protection and larger trials are [underway].” The New York Times reported of ChAdOx1 nCoV-19 that “scientists cautioned that the antibody responses in convalescing patients varied widely, and that even matching those responses did not necessarily guarantee any degree of immunity.” Meanwhile, following the promising results of dexamethasone, Atul Gawande, MD, MPH, a surgeon and chairman of Haven Healthcare, took to Twitter to remind us of “all the retractions and walk backs” we have seen during the COVID-19 pandemic regarding prospective treatments.

There are some similarities between ChAdOx1 nCoV-19 and the Russian vaccine, Sputnik-V. As The Lancet notes, ChAdOxn1 nCoV-19 is “a chimpanzee adenovirus-vectored vaccine (ChAdOx1 nCoV-19) expressing the SARS-CoV-2 spike protein compared with a meningococcal conjugate vaccine (MenACWY) as control.” Sputnik-V, by comparison, “is administered in two doses and consists of two serotypes of human adenovirus, each carrying an S-antigen of the new coronavirus, which enter human cells and produce an immune response” as noted by Al Jazeera.

Put simply, we cannot afford not to be cautious. This is where Russia’s coronavirus vaccine comes in.

Russian President Vladimir Putin. Kremlin.ru / CC BY (https://creativecommons.org/licenses/by/4.0)

The news came when Russian President Vladimir Putin announced on state television on August 12th that “a vaccine against coronavirus has been registered for the first time in the world this morning. I know that it works quite effectively, it forms a stable immunity.” The vaccine, was developed by the Gamaleya Institute in the Russian capital of Moscow. However, as CNN reports, the vaccine is not reported to have yet undergone phase-III trials. This is at the crux of the international controversy over Russia’s coronavirus vaccine.

As epidemiologist Gideon Meyerowitz-Katz explains in an opinion piece published in The Guardian, “phase three trials are the biggest pre-licensure studies, and they test whether the vaccine actually works – they randomly allocate people into two groups, vaccine versus control, and follow them over months to see if the people who received the vaccine get infected less than people who get the control. These trials are huge, with tens of thousands of participants, so they can also look for rare side-effects that the smaller studies cannot pick up.”

Meyerowitz-Katz identifies phase-III trials as “the key thing…until these are completed, all you’ve shown is that the vaccine doesn’t do harm to everybody who takes it, and that there is some antibody response within a month of getting the immunisation at a certain dosage level. There are numerous examples of vaccines that looked promising at phase two – they caused antibody responses and were safe enough – that turned out to be useless at actually preventing disease.” In the example of Sputnik-V, Meyerowitz-Katz explains that “while phase one and two trials of the vaccine have been pre-registered, they are reportedly ongoing and have not yet posted any results. There is no evidence a phase three trial has even been started, never mind completed. This leaves us with the obvious conclusion: no one really knows if this vaccine actually works.”

Russia’s state news agency RT does note that “Russia’s health regulator registered the vaccine after it passed Phase II trials in June and July. It was decided that completing a Phase III trial was not necessary for the initial roll-out because it is based on an already proven platform. However, it’s important to note that Sputnik V won’t go into general circulation until January 2021, allowing another four to five months in which to further observe its effectiveness.”

It is worth noting that the Ebola vaccine, as the World Health Organization (WHO) stated on August 9th, 2015, was still at the stage of “the Phase III trial…continuing” at the time when “randomisation [had] stopped on 26 July, 2015 to allow for all adults in the newly-defined rings to receive the vaccine immediately, and to gather more conclusive evidence on effectiveness of the vaccine and of the ring vaccination strategy…continuation of the clinical trial could contribute to interrupt transmission of Ebola virus in Guinea. Indeed, the “ring vaccination” approach adopted for the clinical trial Ebola ca suffit is based on a strategy used during the eradication of smallpox.”

However, reactions have still been mixed. Science magazine described Russia’s announcement of having approved the world’s first coronavirus vaccine as “a startling and confusing move” and reported that “scientists around the world [have] immediately denounced the certification as premature and inappropriate.” In a statement, geneticist Francois Balloux of University College, London did not mince words, stating “this is a reckless and foolish decision. Mass vaccination with an improperly tested vaccine is unethical. Any problem with the Russian vaccination campaign would be disastrous both through its negative effects on health, but also because it would further set back the acceptance of vaccines in the population.”

In India, All India Institute of Medical Sciences (AIIMS) director Dr Randeep Guliera told The Hindustan Times that “if Russia’s vaccine is successful, then we will have to see critically whether it is safe and effective. There should not be any side effects of the vaccine and it should provide good immunity and protection. India has the capacity for mass production of the vaccine.” Meanwhile, officials in a number of countries, including Brazil, Israel, Kazakhstan, and the Philippines, have expressed cautious interest in the vaccine – including purchasing it and participating in clinical trials.

The World Health Organization (WHO) has said it is in contact with the Russian government regarding Sputnik-V. “We are in close contact with the Russian health authorities and discussions are ongoing with respect to possible WHO prequalification of the vaccine,” said WHO spokesperson Tarik Jasarevic. “Pre-qualification of any vaccine includes the rigorous review and assessment of all the required safety and efficacy data.” He emphasised that “to get this [prequalification], there is a review and assessment of all required safety and efficacy data that are gathered through the clinical trials. WHO will do this for any candidate vaccine.”

Russia, for its part, has hit back at the controversy. “It seems our foreign colleagues are sensing the specific competitive advantages of the Russian drug and are trying to express opinions that…are absolutely groundless,” retorted the country’s Minister of Health Mikhail Murashko. The Minister has added that “within two weeks, the first batch of the vaccine will be released” and that “the domestic market needs are our priority.”

It is worth noting that criticisms have come from within Russia, not just from “foreign colleagues.” The Science article quotes Svetlana Zavidova of the Association of Clinical Research Organizations in Russia, who said “I feel only shame for our country.” She cautioned that “accelerated registration will no longer make Russia a leader in this race, it will only expose end users of the vaccine, citizens of the country of the Russian Federation, to unnecessary danger.”

As my colleague Nicholas Parry wrote for Health Issues India earlier this month, “a rushed and ineffective vaccine could not only prove to have little impact, but diminish confidence in any future vaccines which could in turn reduce the efficacy of vaccination efforts even with an effective vaccine.” This is a key consideration. An ineffective or even dangerous vaccine could fuel a new wave of vaccine hesitancy – a major threat to global health, identified as a major challenge by the WHO.

No-one denies that the world needs a vaccine. But we need a safe and effective one. Unless the rigmarole of studies and the scientific process is undertaken – one Meyerowitz-Katz explains is “not for fun” – we will simply be embarking on a gamble we cannot afford.