In May, there was multiple news surrounding the vaccine development for COVID-19 prevention. As I am writing this blog, seven companies are conducting human clinical trials for their vaccine candidates, nine more that are undergoing preclinical testings.
The news buzz has been around the three top contendents, 1) the US-owned Moderna, 2) the UK-based the University of Oxford with AstraZeneca, and 3) the China-based CanSino Biologics.
Let’s first talk about the vaccine candidate by Moderna. It is a vaccine that is based on novel technologies, using messenger RNA (mRNA) as the active agent for triggering the human adaptive immune response. The phase one clinical trials showed the vaccine’s capability to induce the body to product neutralization antibody at a level that mimicked patients recovered from COVID-19. I have explained the mRNA technology in an earlier blog post.
Despite the promising results, the vaccine research community is slightly skeptical about the press-release result from Moderna. Many scientists would like to review the actual collected data from Moderna.
On Wednesday, June 3rd, the CEO from Moderna, Stephane Bancel, explained to the media that the company withheld prominent data on its COVID-19 vaccine, the mRNA 1273, was due to the federal securities laws and other standards in scientific journals.
The federal securities laws?
This suggests the federal government sees the vaccine as a precious asset that is no longer a matter of health issue, and instead of a subject that matters national security. The last time science research being treated as national security was probably during WWII, the Manhatten Project. It appears that the US government is on a race, but a race against whom?
On the other side of the Atlantic Ocean, the University of Oxford has partnered with AstraZeneca to develop their version of the COVID-19 vaccine. The current candidate’s name is AZD 1222. It’s an investigational vaccine that is based on a recombinant chimpanzee adenovirus (a common cold virus that infects chimpanzees) that is modified to contain the genetic material of the spike protein of the SARS-CoV-2. The spike protein is responsible for binding and entry to human cells that express the angiotensin-converting enzyme 2 (ACE2) receptors. The modified adenovirus is designed to be unable to replicate inside the host body. This technology has been in development for two to three decades.
This vaccine candidate is still in Phase I clinical trial.
In a recent report, AstraZeneca has found manufacturing partners to produce and distribute two billion doses of the vaccine when the authorities approve it. Their effort is not only aiming to benefit people in developed countries. AstraZeneca has also reached a licensing agreement wit an India manufacturer, SII, to produce and supply one billion doses of the vaccines to other developing countries.
Over in China, the researchers from the biotech company, CanSino Biologics are also appeared to be on a race. In comparison, they published their phase I clinical trial results in the famous medical journal, The Lancet. The company reported using a different recombinant adenovirus (human adenovirus type 5) for the expression of the SAR-CoV-2 spike protein. The vaccines showed promising results in inducing the recipients to produce neutralizing antibodies and cellular-based (T-cell) immunity. However, critics were concerned that half of the participants had experienced a fever after the vaccine injection. This vaccine candidate is currently undergoing phase 2 clinical trial.
Which one will win?
If anyone is just looking purely on the timeline for development, it seems like Moderna is in the lead. However, biomedical research is never only about who is leading during the process.
In the development of biological agents, agents that are not synthesized by chemical reactions, a large number of development failures happen at Phase 3 clinical trial. It is the stage where a large number of participants are involved in the testing of product safety and efficacy.
“Can the vaccine stop the virus from infecting human, and with limited adverse effects?”
This is the critical question all drug companies seeking new drug/ vaccine approval has to answer.
My research background is in nucleic acids (DNA and RNA), so I am particularly intrigued by the early success of the mRNA vaccine by Moderna. Although I am also skeptical about their press release, I fully understand the need to protect their technology. In the world of nucleic acid research, the nucleic acid sequence is the essence of the entire investigation. From an industrial standpoint, releasing certain data can be suggestive of the particular mRNA sequence behind the vaccine technology. After investing millions of dollars and countless amount of time, the mRNA technology is no doubt the “top secret” in the company.
However, I cannot hide my skepticism based on my knowledge of the formulation technology behind the mRNA vaccine. The mRNA is packaged in a lipid nanoparticle that is modified with an agent called polyethyleneglycol (PEG). The modification process is commonly called pegylation. Pegylation can improve the drug/ vaccine’s retention time in the body. The slower the body to clear the administered agent, the more the effect it will have. On the other hand, PEG can also be the problem source for trail failure. There have been reports indicating PEG can induce neutralizing antibody productions in the recipients’ bodies. If this phenomenon is observed in a large number of participants during Phase III clinical trials, it will effectively terminate the study.
I believe having healthy competition in the COVID-19 vaccine development is an excellent thing. This means people will have more chances of getting an effective vaccine in the near future—something the human race desperately needs.
We are at an arms race, but the competition is against the coronavirus, not with each other.
Let’s hope we will have at least one winning candidate before the looming second wave of the pandemic.
Written by Dr. Ka Lok Hong, June 6th 2020
