Vaccines ordinarily require several years of research and clinical trials. However, scientists around the world are racing to develop a safe and effective Coronavirus disease 2019 (COVID-19) vaccine within 12 to 18 months. Several different vaccine platforms are being tested for COVID-19, and a handful of vaccine candidates are nearing the end of clinical trials. It is hoped that a safe and effective COVID-19 vaccine will be a viable solution to disperse around the world.
While vaccines typically require several years of research and testing, scientists around the world are racing to develop a safe and effective Coronavirus disease 2019 (COVID-19) vaccine within 12 to 18 months. As of 15th October 2020, the World Health Organization (WHO) has been tracking at least 42 candidate vaccines in clinical trials and 156 candidate vaccines in the preclinical trial phase (1). Nearly a dozen are reaching the final stage of clinical testing.
Vaccines stimulate the production of antibodies in the immune system to protect against one or several diseases. Vaccines are made from either a causative agent of the disease, a subunit, or a synthetic form to emulate a toxic threat (called an antigen) without inducing the disease through the body. As a result, the immune system is alerted to produce antibodies to destroy the threat and any associated microorganisms in the future.
The development of vaccines includes a pre-clinical stage and several phases in clinical trials before approval. (Read more about clinical trials here) Several different vaccine platforms are being tested for COVID-19, including: viral vectors, genetic-based, protein subunits, inactivated, and repurposed vaccines.
Viral vector vaccines consist of viruses engineered to carry some COVID-19 genes. University of Oxford and AstraZeneca were the first to produce a vaccine candidate based on a chimpanzee adenovirus. In May, the vaccine began Phase 3 in Brazil, South Africa, and the United States. On 6th September, AstraZeneca paused all of its multinational clinical trials to investigate an infection one of its volunteers developed. Clinical trials have resumed in recent weeks; however, trials are still on hold in the United States [2]. Johnson & Johnson has used the Adenovirus 26 (Ad26) to produce several vaccines in the past and has also used Ad26 to produce a COVID-19 vaccine [3]. Johnson & Johnson began Phase 3 testing in September but halted their testing on 12th October to investigate safety concerns when a study participant developed an unexplained illness.
DNA and RNA-based vaccines deliver genetic instructions into the cells (of the human host) to produce viral proteins and provoke an immune response against the virus. Moderna began developing a mRNA vaccine in January 2020 and started Phase 3 testing in July around the United States [4]. Pfizer and BioNtech have collaborated with Fosun Pharma to produce a mRNA vaccine as well [5]. Their vaccine began Phase 3 testing in July in various countries, including Argentina, Brazil, Germany, and the United States.
Protein-based vaccines contain viral proteins, either whole proteins or only subunits. Novavax develops vaccines by attaching proteins onto microparticles and created a COVID-19 vaccine in a similar way [6]. The vaccine began Phase 3 testing in September with volunteers from the United Kingdom. A larger Phase 3 trial is projected to start in October with participants from the United States.
Inactivated vaccines are created from weakened or killed-off viruses. Wuhan Institute of Biological Products created an inactivated vaccine, which has been tested by Sinopharm [7]. In July, Phase 3 testing started in the United Arab Emirates and then Peru and Morocco in August. In September, the vaccine received emergency approval for use on health care workers. Beijing Institute of Biological Products also developed an inactivated vaccine that has been tested by Sinopharm as well [8]. The vaccine launched Phase 3 testing in July and received approval for limited emergency use on health care workersin September. Sinovac Biotech is also testing an inactivated vaccine, which launched Phase 3 trials in Brazil, Indonesia, and Turkey in July.
Repurposed vaccines are existing vaccines that were developed for specific diseases, but can potentially protect against other diseases. The Bacillus Calmette–Guérin (BCG) vaccine was developed in the early 1900s to protect against tuberculosis [9]. In March, the Murdoch Children's Research Institute launched Phase 3 testing of BCG against COVID-19. University of Campinas, Brazil also sponsored a clinical trial that began Phase 4 in August. UMC Utrecht began in Phase 4 in August. Hellenic Institute for the Study of Sepsis began phase 4 in May. Radboud University started Phase 4 in April.
While the aforementioned vaccines show promise, there are wide-ranging concerns amongst scientists [10,11]. Most of the clinical trials underway project to publish results in 2021. As a result, there are at least several more months of continuing uncertainty regarding the virus that has claimed millions of lives around the world. It is hoped that a safe and effective COVID-19 vaccine will be a viable solution to disperse around the world. Only time and evidence-based results can prove the efficacy of any viable vaccine.
Author; Millie Zhou MSc EBHC Medical Statistics at Kellogg College
References
1. Draft landscape of COVID-19 candidate vaccines [Internet]. [cited 2020 Oct 18]. Available from: https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines
2. Bloomberg [Internet]. [cited 2020 Oct 18]. Available from: https://www.bloomberg.com/news/articles/2020-10-02/astrazeneca-resumes-vaccine-trial-in-japan-u-s-still-on-hold
3. Johnson & Johnson Initiates Pivotal Global Phase 3 Clinical Trial of Janssen’s COVID-19 Vaccine Candidate [Internet]. [cited 2020 Oct 18]. Available from: https://www.jnj.com/johnson-johnson-initiates-pivotal-global-phase-3-clinical-trial-of-janssens-covid-19-vaccine-candidate
4. Phase 3 clinical trial of investigational vaccine for COVID-19 begins [Internet]. 2020 [cited 2020 Oct 18]. Available from: https://www.nih.gov/news-events/news-releases/phase-3-clinical-trial-investigational-vaccine-covid-19-begins
5. Pfizer and BioNTech Announce Further Details on Collaboration to Accelerate Global COVID-19 Vaccine Development [Internet]. [cited 2020 Oct 18]. Available from: https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-announce-further-details-collaboration
6. Novavax Advances Development of Novel COVID-19 Vaccine [Internet]. [cited 2020 Oct 18]. Available from: https://ir.novavax.com/news-releases/news-release-details/novavax-advances-development-novel-covid-19-vaccine
7. Sinopharm Group (Wuhan Institute of Biological Products) and Chinese Academy of Sciences (Wuhan Institute of Virology) [Internet]. 2020 [cited 2020 Oct 18]. Available from: https://www.genengnews.com/covid-19-candidates/sinopharm-group-wuhan-institute-of-biological-products-and-chinese-academy-of-sciences-wuhan-institute-of-virology/
8. China’s Beijing Institute of Biological Product’s COVID-19 Vaccine Reportedly Ready for Phase III? [Internet]. 2020 [cited 2020 Oct 18]. Available from: https://www.trialsitenews.com/chinas-beijing-institute-of-biological-products-covid-19-vaccine-reportedly-ready-for-phase-iii/
9. Al-Kassmy J, Pedersen J, Kobinger G. Vaccine Candidates against Coronavirus Infections. Where Does COVID-19 Stand? Viruses [Internet]. 2020 Aug 7;12(8). Available from: http://dx.doi.org/10.3390/v12080861