Current state of the pursuit of the vaccine against COVID-19

Summary:

  • There are more than two hundred vaccines in development with more than thirty of them in clinical trials.
  • Ten vaccines have reached the final stages of the clinical trials, where up to 30’000 adult volunteers participate to examine the products’ safety and efficacy.
  • mRNA vaccines are shown to be safe but the achieved immunity may be limited.
  • Viral vector vaccines are the most promising to achieve high and broad protection but may be more prone to safety issues in comparison to other promising candidates, though rarely.
Current state of the pursuit of the vaccine against COVID-19

Currently, SARS-CoV-2 is one of the most important issues of the global community due to its threat to human health. Economic burden should be also considered due to its long lasting effect on job markets and small/middle size businesses to say the least. The majority of infected individuals may undergo asymptomatic infections or develop a mild illness with fever, tiredness, and cough. Difficulty of breathing and loss of sense of smell and taste are observed. In the most severe cases, the infection can be life-threatening or leave long-term effects [1]. The infection rate is progressing with unprecedented speed, meaning more people will suffer from the infection in the near future. Vaccines have been shown to be the practical and the most cost-effective solution to protect the majority of people from pathogens in the long run. In this article, we present leading vaccine candidates in order to familiarize readers with the approaches taken by scientists around the world to solve this problem.

 There are more than two hundred vaccine candidates in development. Thirty nine are now being tested on people in clinical trial settings, which we described in one of our previous articles (Clinical Trials). Ten of them have successfully reached the last stage of clinical multicenter phase 3, where usually up to 30’000 volunteers aged 18-85 participate with an inclusion of a placebo control [2]. With an exception of the Russian vaccine Sputnik V, each of the aforementioned vaccines is following standard, though administratively compressed, process [3].

Some of the most discussed vaccine candidates are mRNA-based vaccines, in which recipient’s cells are instructed to produce a small part of the virus themselves to train the immune system (mRNA vaccines). The leaders are BioNTech/Pfizer’s BNT162 and Moderna’s MRNA which are currently in the final phase of clinical testing [4, 5]. The technology is promising due to the lack of frequent or severe safety issues present in clinical trials and potential rapid manufacturing in the time of pandemic. Unlike cell-based vaccines, the mRNA can be promptly generated or changed in vitro thanks to utilization of extremely efficient enzymes such as RNA polymerase [6]. On the downside, it is not fully known whether the vaccines will induce strong immunity in the lung tissue, a major infection site of SARS-CoV-2.

 The other promising candidates that have reached the third phase of clinical testing are so called viral vectors. Such vaccines contain genetically engineered viruses, e.g. different human or animal adenoviruses, with characteristic SARS-CoV-2 proteins on their surface. They tend to generate stronger immune response, including within the lung tissue. ChAdOx1 nCoV-19 (or AZD-1222), developed by the University of Oxford and AstraZeneca, is based on chimpanzee adenovirus, and may achieve broad immune response. Whereas Ad26-S (Janssen Pharmaceutical), Ad5-nCoV (Cansino Biologics) and Sputnik V (Gameleya Research Institute), which contain human adenoviruses, may be less effective. A fraction of people might have come into contact with the viruses already. Thus, the strongest response in recipients will target their human adenovirus components instead of the SARS-CoV-2 proteins [8]. These types of vaccines are relatively safe. However, at the beginning of September AstraZeneca paused all the ChAdOx1 nCoV-19  trials temporarily due to unexpected illness, with symptoms of transverse myelitis, in order to investigate the causation [9]. This illustrates that, despite potential political pressure, the safety concerns are being addressed according to the protocol. Conversely, Sputnik V received surprisingly early approval in August 2020 for distribution in Russia before finalizing all the clinical trials [3].

 Other candidate vaccines are being developed in a form of inactivated virus, which are usually administered with adjuvants (additional pharmacological substance) in order to enhance immunological response. Thus, they are not suitable for delivery to lungs and may be prone to some safety concerns [10]. These types are being developed mostly in China, India and Kazakhstan [2].

This is not an exhaustive list of potential vaccines and it only gives a general notion of them. For further reading please see reference 2. In summary, there is a strong effort on the line between the scientific community, pharmaceutical companies and regulatory agencies to bring safe and effective vaccines against SARS-CoV-2. As of November 2020, BioNTech/Pfizer’s BNT162 was shown to be 90% effective based on the interim results [11]. Likely, the vaccines may be mainly used within the developed countries due to the storage requirements [6]. In regions with insufficient distribution mechanisms adenovirus-based vaccines may be prefered. In any case, it is believed that the vaccines will be administered first to healthcare workers or vulnerable ones and later on to the general population. In the near future this will prevent overburdening of the hospitals and excess of death of the vulnerable population. In the long run, hopefully the transmission of the virus will be broken and the SARS-CoV-2 outbreaks will happen more infrequently.

References:

  1. Azer S.A. COVID19: pathophysiology, diagnosis, complications and investigational therapeutics. New Microbes New Infect 37, (100738) (2020).
  2. https://www.covid-19vaccinetracker.org/
  3. Burki K. T.: The Russian vaccine for COVID-19. Lancet 8, (11): e85-e86.
  4. ClinicalTrials.giv – NCT04470427, A Study to Evaluate Efficacy, Safety, and Immunogenicity of mRNA-1273 Vaccine in Adults Aged 18 Years and Older to Prevent COVID-19.
  5. https://biontech.de/science/pipeline
  6. Pardi N., Hogan M.J., Porter F.W., Weissman D. mRNA vaccines – a new era in vaccinology. Nat Rev 17:261-279 (2018).
  7. Leticia Moreno-Fierros , Ileana García-Silva & Sergio Rosales-Mendoza: Development of SARS-CoV-2 vaccines: should we focus on mucosal immunity?, Expert Opinion on Biological Therapy, 20, (8): 831-836 (2020).
  8. Zhang S., Huang W., Zhou X., Yhao Q., Wang Q., Jia B.: Seroprevalence of Neutralizing Antibodies to Human Adenoviruses Type-5 and Type-26 and Chimpanzee Adenovirus Type-68 in Healthy Chinese Adults. J. Med. Virol. 85:1077-1084 (2013).
  9. Mallapaty S., Ledford H.: COVID-vaccine results are on the way – and scientists’ concerns are growing. Nature 586, 16-17 (2020).
  10. Lingbin Z.: Mucosal adjuvants: Opportunities and challenges, Hum Vaccin Immunother 12, (9): 2456-2458 (2016).
  11. https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-announce-vaccine-candidate-against