Lynne Xu, Torrey Pines High School
Part of the Collaboration with JOURNYS
It has been six months since the SARS-COV-2 virus emerged in China, and since then, there have been over 9 million confirmed cases worldwide and the virus has swept through over 180 countries. Currently, there is no known cure for COVID-19. In order to delay the spread of COVID-19, the United States has imposed social distancing rules and shut down businesses, leading to a meltdown of the US economy. As of now, over 38 million people in the US have filed for unemployment. A history of viral pandemics tells us that an effective vaccine for the virus is needed urgently to stop COVID-19 and resume normal life. For example, in 1953, the successful development of the polio vaccine by the hero Dr. Jonas Salk, the founder of the local Salk Institute for Biomedical Research, effectively eradicated the polio virus, saving thousands of children’s lives worldwide.
Research done with coronaviruses show that the viruses infect cells with their “spike” glycoprotein. The spike protein of the coronavirus binds to the receptor on the surface of a human cell, allowing the genetic material of the virus to enter. Scientists believe finding a way to prevent the virus from binding can help fight the virus [1]. Some progress has been achieved in finding neutralizing antibodies to stop viral entry into cells and clear the virus by the immune system [2].
The permanent solution, however, remains in the development of effective vaccines for SARS-CoV-2. There are many different types of vaccines being developed, including recombinant-protein vaccines, viral vector vaccines, DNA vaccines, mRNA vaccines, live vaccines, or inactivated virus vaccines. In this case recombinant-protein vaccines involve injecting purified proteins of the spike protein into a person. Viral vector vaccines involve a virus such as an adenovirus; most viruses being tested currently use a weakened cold virus to deliver genetic material to cells in the body. In DNA vaccines, a plasmid is injected into a human; the plasmid codes for many SARS-CoV-2 viral proteins, including the spike protein. In mRNA vaccines, mRNA for coding for viral proteins (the body synthesizes proteins by itself) are injected into the body.
Pre-clinically, over 100 vaccines are being developed by institutions and companies worldwide. The frontrunners in vaccine research are Moderna, Oxford/Astrazeneca, CanSino, and Inovio, who are in the process of their phase I or II trials, and many planning phase III trials.
So far, one vaccine that has potential positive outcomes is Moderna’s mRNA-1273 vaccine. The company has not tested the drug on primates but said that the vaccine did elicit an immune response to the virus in rodents. The company recently completed its Phase I clinical trial, which was to determine the safety of the vaccine. It released data from eight phase I trial participants, showing an immune response with the production of anti-viral antibodies. After a repeated vaccination, their antibodies levels were near the levels of individuals recovering from COVID-19 [3]. Moderna has now initiated a Phase II trial, which is to test the efficacy of vaccination against virus. The Phase II trial will include 600 adult patients, half under 55 years old. The company predicts that the Phase III trial can begin as early as July [4].
Another vaccine that had promising results is ChAdOx1, developed by scientists at the Jenner Institute of Oxford University. It is an adenovirus vaccine; it uses a weakened cold virus to deliver genomic material of SARS-CoV-2 to human cells, which produces the spike protein of the coronavirus to induce immune responses. The vaccine had only been tested in rhesus macaque monkeys. The study showed that the vaccination prevented pneumonia in six monkeys [5]. However, vaccinated monkey’s noses contained as much virus as those of unvaccinated monkeys, indicating that the vaccine may not fully protect against viral infections. The monkey study shows no safety concerns about the vaccine. The Oxford group has initiated Phase I trials [4].
CanSino also developed an adenovirus vaccine with the vector Ad5, which was determined safe in humans. A study published earlier this month showed participants generated an immune response and the vaccine was well tolerated at different dosages with no serious adverse effects within 28 days after vaccination [6]. However, the heightened immune response could be due to the individual’s pre-existing immunity to the adenovirus. A phase II trial has been started to confirm the efficacy and long-term adverse effects. It is expected to include about 500 adults [7].
Inovio is developing a DNA vaccine called INO-4800. In a DNA vaccination, a plasmid is injected into a human; in this case, the plasmid encodes for many SARS-CoV-2 viral proteins, including the spike protein. In early May, the company published results showing T cell activation and antibody responses in mice and guinea pigs [8]. The vaccine is currently in a phase I trial with 40 participants. The results of the trial are expected in June, and the company is planning a phase II/III study during the summer [7].
The US and other countries around the world have pledged millions of dollars to vaccine development in an effort to bring an effective vaccine to the market at the end of 2020. Scientists believe that an effective vaccine could take at least six more months of testing. Researchers are making great efforts in condensing "10 years of vaccine development and testing into a matter of months” [9]. Whether it be a few months, a year, or two years, huge improvements are occurring in the field of vaccine development every day, with the hope that society can one day get back to “normal”.
References
[1] Wrapp, D., Wang, N., Corbett, K. S., Goldsmith, J. A., Hsieh, C. L., Abiona, O., ... & McLellan, J. S. (2020). Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science, 367(6483), 1260-1263.
[2] Jiang, S., Hillyer, C., & Du, L. (2020). Neutralizing antibodies against SARS-CoV-2 and other human coronaviruses. Trends in immunology.
[3] Lewis, T. (2020, May 22). Early Coronavirus Immunity Data Fuel Promise for a Vaccine. Retrieved from http://www.scientificamerican.com/article/early-coronavirus-immunity-data-fuel-promise-for-a-vaccine/.
[4] Callaway, E. (2020, May 21). Coronavirus Vaccine Trials Have Delivered Their First Results-but Their Promise Is Still Unclear. Retrieved from http://www.scientificamerican.com/article/coronavirus-vaccine-trials-have-delivered-their-first-results-but-their-promise-is-still-unclear1/.
[5] van Doremalen, N., Haddock, E., Feldmann, F., Meade-White, K., Bushmaker, T., Fischer, R. J., ... & Clark, M. H. (2020). A single dose of ChAdOx1 MERS provides protective immunity in rhesus macaques. Science Advances, eaba8399.
[6] Zhu, F. C., Li, Y. H., Guan, X. H., Hou, L. H., Wang, W. J., Li, J. X., ... & Jia, S. Y. (2020). Safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 vectored COVID-19 vaccine: a dose-escalation, open-label, non-randomised, first-in-human trial. The Lancet.
[7] What are the Top 5 most promising COVID-19 vaccine candidates? (n.d.). Retrieved from https://allianceforscience.cornell.edu/blog/2020/05/what-are-the-top-5-most-promising-covid-19-vaccine-candidates/
[8] Smith, T. R., Patel, A., Ramos, S., Elwood, D., Zhu, X., Yan, J., ... & Xu, Z. (2020). Immunogenicity of a DNA vaccine candidate for COVID-19. Nature Communications, 11(1), 1-13.
[9] Steenhuysen, J. (2020, May 23). Exclusive: U.S. plans massive coronavirus vaccine testing effort to meet year-end deadline. Retrieved from http://www.reuters.com/article/us-health-coronavirus-usa-vaccine-exclus/exclusive-u-s-plans-massive-coronavirus-vaccine-testing-effort-to-meet-year-end-deadline-idUSKBN22Y2L3