May 15, 2020
An overview of the current scientific progressions of SARS-CoV-2 vaccine candidates.
As the COVID-19 pandemic continues to sweep across the world, one question seems to be at the forefront of everyone’s minds. When will we see a vaccine for the virus? That very same question has led scientists from all over to put a halt to their normal day-to-day operations and unify in the fight against SARS-CoV-2. An effective vaccine may typically take years or even decades to produce. However, with the tireless efforts of the global scientific community, a vaccine can potentially be seen as early as 2021.
Shortcuts to Approval
To accelerate the timeline of a vaccine’s production by years, teamwork and compromise are essential. Regulating bodies, such as the United States Food and Drug Administration (FDA), are working with scientists to minimize any obstacles that may delay the process of clinical trials. Creating a more efficient screening and volunteer recruitment system alone may save scientists months of time, according to virology expert Andino-Pavlovsky. Additionally, if any vaccine passes safety tests and shows promise in initial phases of clinical trials, the FDA has the ability to approve that vaccine for emergency use and forgo further clinical trials. If the FDA chooses to implement any vaccine candidate for emergency use, the timeline for production will be significantly shorter than the already accelerated expected predictions. (1)
In congruence with the FDA, organizations such as the U.S. Department of Health and Human Services (HSS) and the Biomedical Advanced Research and Development Authority (BARDA) are working with research teams to make the transition between safety testing and clinical trials as smooth as possible. BARDA will be funding the manufacturing needed to produce thousands of vaccine doses used during clinical trials for multiple US based research teams. (2) Unlike the normal timelines for a vaccine, preparations for these COVID-19 vaccine tests are being made before any candidate even enters the clinical trial phase. This allows the immediate transition from safety testing to clinical testing, potentially reducing production time by months. (1)(2)
Obstacles Scientists Face
With the production of any vaccine, the safety of the general public must come first. As scientists race against the clock to fight SARS-CoV-2, we must be reminded of the meticulous process any candidate vaccine must go through to ensure not only its effectiveness against a virus, but it's harmlessness towards the human body. Factors to consider are: complications due to vaccine usage, the durability of immunity, and accounting for the wide range of demographics that will be treated with a vaccine. (3)
While animal models may demonstrate that a candidate vaccine is effective at preventing viral infections, research must make certain that secondary issues do not arise. Particularly with infections of the respiratory system, damage to the lungs by way of vaccine injection may lead to equally as dangerous outcomes as the virus itself.
The duration of a vaccine’s effect must also be taken into account in the production process. With much speculation about the potential seasonality of SARS-CoV-2, an effective vaccine should provide humans with long-term immunity from the virus. Research into the durability of immunity for a vaccine candidate will take, at minimum, a few months to conduct properly. (1)(3)
Creating a vaccine that protects those most at risk, while not harming others is also a challenge. COVID-19 has displayed much more severe symptoms in the demographic over the age of 50. However, individuals in this demographic also do not produce a strong immune response to vaccines in comparison to younger groups on average. (3) This leads scientists to the obstacle of finding a balance between creating a specific vaccine that will produce an immune response in our immunocompromised populations, and not adversely affecting the remaining vaccine users.
What Types of Vaccines Are Being Tested?
The typical vaccine takes the form as a weakened or dead version of a virus that will be directly injected into patients. This injection will cause the patient’s immune system to react to the foreign antigens that have entered the body and produce antibodies to fight off the infection.(14) While efficient, conventional vaccine models can be time and labor intensive. (1) (4) Such a process requires the proper culturing and modifying of massive amounts of live virus samples that will eventually enter animal testing. These steps alone can add months or more on the total timeline of a vaccine’s production. (1)(5) Due to the time-sensitive nature of producing a COVID-19 vaccine, researchers are veering from this traditional approach. Some vaccine candidates showing promise are using a synthetic mimic, or non-replicating viral vector, of the virus as opposed to an actual sample of the virus. By creating a vector, scientists are still producing a strong antibody response from the immune system without the hassle of working with live virus samples. (4)(12)
An unconventional approach also used in the race against the virus is the novel class of mRNA vaccines. mRNA is the genetic material that leads to the production of specific proteins. The basic premise behind an mRNA vaccine is that creating the genetic material found in proteins that cover the surface of SARS-CoV-2 can lead to a strong immune response without the presence of the actual virus. (1) As with the synthetic mimic vaccines, mRNA vaccines avoid that time spent culturing live viruses. Additionally, mRNA vaccines can be administered at lower doses and can produce millions of doses in just a few liters of sample. (4)(15) This is especially important, as faster global scaling and production rates equate to more people receiving the vaccine sooner rather than later.
Leading Vaccine Candidates
It would be beneficial to first discuss the possible clinical stages a vaccine candidate may be in before listing the progress of current leading candidates. There are 4 main phases in the clinical development of vaccines: (3)(6)
· Phase 1 - Very small human trials are conducted
· Phase 2 - Volunteer group is expanded and will now include demographics that the vaccine is intended for (elderly and immunocompromised for COVID-19)
· Phase 3 - Vaccine is then tested amongst thousands of individuals with varying demographics to further test safety and efficiency
· Phase 4 - After a vaccine is approved, testing will continue over time
Credit: Jen Christiansen
As of May 15, 2020, we have one candidate vaccine in phase 3 clinical testing. Originally used as a pediatric Tuberculosis (TB) vaccine, ‘Bacillus Calmette-Guerin (BCG) live-attenuated vaccine for COVID-19’ has been linked with positive correlation with prevention of acute respiratory infections among the elderly. (7)(8) A recent publication from medRvix explored the relationship between countries with BCG vaccination policies and lower morbidity and mortality rates than countries that do not implement these policies. It was also found that countries, such as Iran, that began BCG vaccination programs relatively recently (1984) had a steeper mortality rate than countries with longstanding programs. This indicates that BCG potentially offers strong protection to elderly populations. (9) However, it must be noted that these exciting statistics from the medRvix article are still in the preprint stages and are in the process of receiving peer-review. The vaccine is currently recruiting thousands of volunteers for phase 3 testing in Australia and the Netherlands and is in early testing phases in the United States. (8)(10)
Not far behind BCG is mRNA-1273 out of the United States. Moderna, the biotech company working in conjunction with National Institutes of Allergy and Infectious Disease, is currently preparing for phase 2 trials to begin shortly with phase 3 trials expected to follow this summer. (11)(12) US regulating bodies are helping to fund the production of the vaccine and have greatly accelerated the process. If this mRNA vaccine would be approved, provisions are already in place to scale it on a global level for distribution. With many candidates accelerating through clinical trials this month, the current landscape of vaccine progression is rapidly evolving. As of May 15th, many vaccines are either awaiting clearance to begin human testing or approval to advance to larger clinical studies.(2) Additional vaccines in, or soon to be in, phase 2 or 3 of clinical trials include INO-4800 (Inovio Pharmaceuticals Beijing, DNA-based), ChAdOx1(University of Oxford, Viral mimic), and Ad5-nCoV (CanSino Biologics Beijing, Viral mimic). An expansive view of the progress of all vaccine candidates in human clinical trials can be found in the chart below. In total, over 12 vaccine candidates are in human trials with well over 80 more currently in preclinical development. (8)(10)(11)(12)(13)(14)
Where We Currently Stand
With the around-the-clock research being conducted on COVID-19 and the seemingly endless global support from the scientific community, a vaccine may be available to the public as early as 2021(15). This unprecedented timeline is dependent on the continued success of clinical trials and assistance from regulating bodies and manufacturers alike. As our scientists and healthcare workers do everything in their power to fight this virus, it is our job to remain as safe as possible. Frequent hand washing, minimizing hand contact to the face, and following local health guidelines should all be practiced.
1. Lanese, Nicoletta. “When Will a COVID-19 Vaccine Be Ready?” LiveScience, Purch, 16 Apr. 2020, www.livescience.com/coronavirus-covid-19-vaccine-timeline.html.
2. U.S. Department of Health and Human Services. “HHS Accelerates Clinical Trials, Prepares for Manufacturing of COVID-19 Vaccines.” HHS.gov, US Department of Health and Human Services, 30 Mar. 2020, www.hhs.gov/about/news/2020/03/30/hhs-accelerates-clinical-trials-prepares-manufacturing-covid-19-vaccines.html.
3. “Get the Facts about a COVID-19 (Coronavirus) Vaccine.” Mayo Clinic, Mayo Foundation for Medical Education and Research, 8 May 2020, www.mayoclinic.org/diseases-conditions/coronavirus/in-depth/coronavirus-vaccine/art-20484859.
4. Kalema, et al. “RNA Vaccines: a Novel Technology to Prevent and Treat Disease.” Science in the News, 10 July 2015, sitn.hms.harvard.edu/flash/2015/rna-vaccines-a-novel-technology-to-prevent-and-treat-disease/.
5. Leakey, Sam, et al. “A Leading COVID-19 Vaccine Scientist Answers Our Questions.” World Economic Forum, www.weforum.org/agenda/2020/05/covid19-vaccine-researcher-questions/.
6. “Vaccine Testing and Approval Process.” Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, 1 May 2014, www.cdc.gov/vaccines/basics/test-approve.html.
7. “BCG Vaccination to Protect Healthcare Workers Against COVID-19 - Full Text View.” BCG Vaccination to Protect Healthcare Workers Against COVID-19 - Full Text View - ClinicalTrials.gov, clinicaltrials.gov/ct2/show/NCT04327206?term=bcg&cond=covid-19&draw=2.
8. “COVID-19 Vaccine Tracker.” Regulatory Affairs Professionals Society (RAPS), www.raps.org/news-and-articles/news-articles/2020/3/covid-19-vaccine-tracker.
9. Miller, Aaron, et al. “Correlation between Universal BCG Vaccination Policy and Reduced Morbidity and Mortality for COVID-19: an Epidemiological Study.” MedRxiv, Cold Spring Harbor Laboratory Press, 1 Jan. 2020, www.medrxiv.org/content/10.1101/2020.03.24.20042937v1.
10. “COVID-19 Vaccine & Therapeutics Tracker.” COVID-19 Vaccine Tracker, biorender.com/covid-vaccine-tracker.
11 Molteni, Megan. “Front-Runners Emerge in the Race for a Covid-19 Vaccine.” Wired, Conde Nast, www.wired.com/story/frontrunners-emerge-in-the-race-for-a-covid-19-vaccine/.
12. “COVID-19 Treatment and Vaccine Tracker.” Milken Institute, milkeninstitute.org/covid-19-tracker.
13. “COVID-19: Vaccine Trials and Antibody Testing Provide Fresh Hope.” Medical News Today, MediLexicon International, www.medicalnewstoday.com/articles/covid-19-reasons-for-hope-vaccine-trials-take-center-stage#First-volunteers-enter-U.K.-vaccine-trial.
14. Callaway, Ewen. “The Race for Coronavirus Vaccines: a Graphical Guide.” Nature News, Nature Publishing Group, 28 Apr. 2020, www.nature.com/articles/d41586-020-01221-y.
15. Schmidt, Charles. “Genetic Engineering Could Make a COVID-19 Vaccine in Months Rather Than Years.” Scientific American, Scientific American, www.scientificamerican.com/article/genetic-engineering-could-make-a-covid-19-vaccine-in-months-rather-than-years1/.