COVID-19 has forced us all to accustom to a new ‘normal’ with several challenges.
Luckily for the world of medical research, uncertainty is not new. However, the consequences and wide-spread panic of this novel coronavirus has mandated a timely development and deployment of an effective vaccine from world leaders and researchers of infectious diseases.
Before delving into vaccine development trial specifics, let’s go over the pathology and epidemiology of the SARS-CoV-2 virus, more commonly referred to as COVID-19. Each virus is unique in its ability and its course of reproduction within the host. For COVID-19, the spike surface glycoprotein binds to the host via receptor binding domains of the angiotensin converting enzyme-II (ACE-II), which is most abundant in type II alveolar cells typically found in the lungs (Xiaofeng et al., 2020). After a SARS-CoV-2 molecule attaches to its target cell, the virion releases RNA into the cell, initiating the replication process of the virus, which continues to disseminate (Xiaofeng et al., 2020). The virus primarily targets the upper respiratory tract and with continues infection, progresses to the bilateral lung lobes. It mimics pneumonia in mild cases, ARDS in severe cases, and can also progress to sepsis (John Hopkins, 2020). As the immune system battles the virus, the body is left susceptible to secondary infections resulting in a superinfection with severe medical consequence (John Hopkins Medicine, 2020). There are currently 6.5 million cases confirmed world-wide, with 390,000 associated deaths (John Hopkins, 2020). Canada has a total of 94,000 cases and 7,500 deaths, which is substantially less than the SARS virus in the early 2000s, which killed 44 Canadians (John Hopkins University, 2020).
The prestigious Lancet journal outlines 10 distinct vaccine trials that have progressed to clinical trials around the world. Vaccine development is a long process, just like any drug development. For example, the U.S. Food and Drug Administration (FDA) only approved a vaccine against the Ebola virus in 2019, which is forty-three years after the deadly virus was discovered (Mullard, 2020). Vaccinologists have made little progress with HIV and respiratory syncytial virus (RSV), despite huge monetary investments towards the development of an effective prophylactic treatment. On average, it takes 10 years to develop a vaccine which can be confidently used on human participants (Mullard, 2020). With the COVID-19 crisis in full swing, many are hoping a vaccine will be developed much quicker than previous attempts in history.
There are several clinical trials being initiated around the globe. I will briefly discuss two prominent studies that focus on vaccine development, that are moving into the final phases of clinical trial.
Trial #1- Oxford University & AstraZeneca Pharmaceuticals – Phase 2b/3
The vaccine termed ‘ChAdOx1 nCoV-19’ has shown promise in the early stages of development and has now progressed into phase 2/human trials.
ChAdOx1 nCoV-19 is developed from the weakened adenovirus virus (ChAdOx1), otherwise known as the common cold. ChAdOx1 causes infections in chimpanzees but has been genetically changed to make it impossible for human replication (University of Oxford, 2020). In order to target SARS-CoV-2, proteins used to make spike glycoproteins from the SARS-CoV-2 molecule are added to the ChAdOx1 construct (University of Oxford, 2020). This protein is found on the surface of SARS-CoV-2 and plays an essential role in the infection pathway of COVID-19.
The phase one trial in healthy adult volunteers began in April 2020 with more than 1,000 immunizations and all follow-ups completed. The next phase enrolled a total of 10,260 adults and children. Phase 2 studies employ expanded participant age ranges to include a small number of older adults (ages 56-69, age 70 and older) and younger children (ages 5-12) (University of Oxford, 2020). For the age groups, researchers will assess the immune response to the vaccine in order to assess a relationship between age and immune system response.
The phase three component of the study will assess vaccine efficacy and infection prevention in an even larger adult population. Adult participants in both the Phase II and Phase III groups will be randomized to receive one or two doses of either the ChAdOx1 nCoV-19 vaccine or the control vaccine, a licensed vaccine (MenACWY) used for combatting the meningococcal bacteria that causes meningitis and septicemia (University of Oxford, 2020).
Trial #2 – Moderna & National Institute for Allergy and Infectious Diseases (NIAID) – Phase 2/3
Moderna, Inc. along with the Vaccine Research Center (VRC) in the National Institute of Allergy and Infectious Diseases (NIAID), has started dosing the first human participants in all age cohorts of the Phase II clinical trial of its COVID-19 vaccine candidate, mRNA-1273. This molecule is a messenger RNA (mRNA) vaccine encoding for a pre-fusion stabilized form of the spike protein (Clinical Trials Arena, 2020).
In the Phase I trial of the vaccine candidate, 25 micrograms (μg) first dose and 100 μg second dose, demonstrated neutralizing antibody titers at or above convalescent sera, and were observed to be generally well tolerated (Clinical Trials Arena, 2020).The Phase II trial will assess the safety, reactogenicity (adverse events that are common and known to occur for the intervention/investigational product being studied) and immunogenicity (the immune response by an organism against a therapeutic antigen) of the two dosages of mRNA-1273, administered 28 days apart. It is set to involve 600 healthy individuals across the age groups of 18-55 and 55 and above, to assess the efficacy in young and middle-aged adults versus older adults (Clinical Trials Arena, 2020). Participants will receive one of the following regimens: two 50 μg doses, two 100 μg doses, or two placebo doses. They will be followed for 12 months after the second vaccination (Clinical Trials Arena, 2020).
Both trials have shown promise in the global fight against COVID-19. While this article only briefly touches on the main findings of these two trials, I encourage you to further investigate them as well as other current literature, as new trials work their way through the developmental pipeline.
In closing, I want to personally thank all health care providers, particularly the sometimes underappreciated Respiratory Therapists around the world, for their dedication and service during these unprecedented times.
Clinical Trials Arena. (2020 June 01). Moderna starts dosing in Phase II Covid-19 vaccine trial.
Retrieved from https://www.clinicaltrialsarena.com/news/moderna-phaseii-vaccine-trial/
John Hopkins University. (2020 June 04). Corona Virus Resource Centre.
Retrieved from https://coronavirus.jhu.edu/news
Mullard, A. (2020 June 06). COVID-19 vaccine development pipeline gears up.
Retrieved from https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31252-6/fulltext
University of Oxford. (2020 May 22). Oxford COVID-19 vaccine to begin phase II/III human trials.
Retrieved from http://www.ox.ac.uk/news/2020-05-22-oxford-covid-19-vaccine-begin-phase-iiiii-human-trials
Xu, Zhe et al. (2020 April 20). Pathological Findings of COVID-19 associated with acute respiratory distress syndrome.
Retrieved from https://www.thelancet.com/journals/lancet/article/PIIS2213-2600(20)30076-X/fulltext
Yoshikawa, A. et al. (2020 May 14). Lung nontumor infections Coronavirus disease 2019.
Retrieved from http://www.pathologyoutlines.com/topic/lungnontumorcovid.html
Zhai, X. et al. (2020 May 20). Comparison of SARS-CoV-2 spike protein binding to ACE2 receptors from human, pets, farm animals, and putative intermediate hosts.
Retrieved from https://jvi.asm.org/content/early/2020/05/14/JVI.00831-20/article-info