World's first COVID-19 vaccine: long-expected salvation or a premature celebration?

Author: Ivana Mišová, PhD.

Published at: 08/13/2020

The announcement from August 11 of the first registered COVID-19 vaccine by the Russians took the whole world by surprise1. From the first glance, this is the news we have all been waiting for – finally a vaccine ready to combat the ongoing pandemic. But is it, truly? What do we really know about the vaccine?

First, let's have a look at the process of vaccine testing. Approved vaccines are among the safest medical products thanks to rigorous testing of their safety and effectiveness. Before a candidate vaccine can be tested on humans, it undergoes preclinical testing on animals, such as rodents and primates, where the researches look for an immune response. After successful preclinical testing, the candidate vaccine is tested in clinical trials, which consist of three phases. In phase 1, the vaccine is given to a small number of people (dozens) to test safety and dosage as well as to confirm that it produces an immune response.  Phase 2 involves hundreds of people from various groups to see how it acts in the target population. It further tests the vaccine's safety and stimulation of the immune system. Phase 3 monitors toxicity, immunogenicity, and serious adverse effects on a much larger scale (thousands of participants). The vaccine needs to be safe and effective before being submitted for approval. Once approved, phase 4 clinical trials continue to monitor data on vaccine usage, adverse effects, and long-term immunity.

The Russian vaccine is named Sputnik V (previously Gam-COVID-Vac)2. It has been developed by the Gamaleya National Center of Epidemiology and Microbiology. Here is what the manufacturers claim: it is an adenoviral-based vaccine that uses two different vectors (rAd26 and rAd5) – carriers – of a gene coding the S protein of SARS-CoV-2. The S protein forms the spike of the virus, which is the part that the coronavirus uses to get into a cell. The first vaccination introduces one of the vectors into our cells. Our body synthesizes the S protein, which induces immune reaction and production of antibodies. The second vaccination uses a different vector and is meant to boost the immune response and provide long-lasting immunity3. In theory, it sounds wonderful. But what is the evidence behind its approval?

Truth be told, there is not much. Based on the available data from the clinical trials registry, Gam-COVID-Vac has been tested in two Phase 1/ Phase 2 clinical trials, on 38 participants each4,5. Though the clinical trials claim to have finished, there are no results posted. Since then, the results have been published in The Lancet. The tested vaccine induced a strong immune response in all 76 participants and was well tolerated6. However, for regulators such as the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA), data on immune response alone would not generally be an adequate basis for approving a vaccine. This is due to the fact that immune response is not necessarily directly proportional to the degree of protection, which can be found out only in large-scale trials7. [Updated on Sept 8, 2020]

The official website of Sputnik V describes a Phase 3 clinical trial starting this month involving “more than 2,000 people”8. This number is much lower than the estimated enrollment for phase 3 clinical trials testing other candidate vaccines, such as Sinovac's PiCoVacc (8,870 participants) or Moderna's mRNA-1273 (30,000 participants)9,10. Is it wise to approve a vaccine tested only for two months in dozens of people?

The answer from the global scientific community seems to be clear – no. Both the scientific community as well as other vaccine developers have strongly urged caution as they have seen no evidence that suggests that Sputnik V is safe and effective. Phase 3 trial is a crucial part of vaccine testing that could reveal side effects that may not have shown up in a small number of volunteers in the earlier phases. Estimates show that only half of the candidate vaccines that successfully pass phase 2 trials are approved after phase 311. Despite the global critique, the Russians plan to start with vaccinating their population in the following months, starting with health care workers and teachers. They even claim to have received requests for over 1 billion doses od the vaccine from 20 states12. While the whole world desperately waits for a vaccine to avert the current crisis, the race for a COVID-19 vaccine should not be won at the cost of our health and safety.

Our project AIM also monitors the development of COVID-19 vaccines. Currently, there are 78 candidate vaccines in our database. Some of the most promising substances are The University of Oxford's AZD1222, Sinovac's PiCoVacc, Moderna's mRNA-1273, and CanSino Biological's Ad5-nCoV.

 

References

    1. https://tass.com/society/1188135
    2. https://sputnikvaccine.com/
    3. https://sputnikvaccine.com/about-vaccine/
    4. https://clinicaltrials.gov/ct2/show/NCT04436471?term=vaccine&cond=covid-19&draw=4
    5. https://clinicaltrials.gov/ct2/show/NCT04437875?term=vaccine&cond=covid-19&draw=4
    6. Y. Logunov et al., “Safety and immunogenicity of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine in two formulations: two open, non-randomised phase 1/2 studies from Russia,” Lancet, vol. 0, no. 0, Sep. 2020.
    7. K. Burki, “The Russian vaccine for COVID-19,” Lancet Respir. Med., vol. 0, no. 0, Sep. 2020.
    8. https://sputnikvaccine.com/about-vaccine/clinical-trials/
    9. https://clinicaltrials.gov/ct2/show/NCT04456595?term=vaccine&cond=covid-19&draw=2
    10. https://clinicaltrials.gov/ct2/show/NCT04470427?term=vaccine&cond=covid-19&draw=5
    11. Chi Heem Wong, Kien Wei Siah, Andrew W Lo, Estimation of clinical trial success rates and related parameters, Biostatistics, Volume 20, Issue 2, April 2019, Pages 273–286, https://doi.org/10.1093/biostatistics/kxx069
    12. https://tass.com/society/1188259