A New Age of Vaccines
By: Krish Patel
With nearly 4 million cases and 286,000 deaths inflicted by the novel coronavirus, COVID-19 (SARS-CoV-2), the pressing need for a vaccine is only growing. Each day over 75,000+ new cases accumulate, with the United States supplying roughly one-third of that number daily.
COVID-19 is a novel strain of SARS CoV, which caused the Severe Acute Respiratory Syndrome pandemic from 2002-2004. The overwhelming consensus is that this virus originated from bats, leaving humans unprepared causing the swift escalation to the pandemic we now face. Both these diseases are in the family of Coronavirus; meaning a crowned/hallo virus based on the microscopic view. According to the Centers for Disease Control, these two viruses share about 80% of their RNA; it’s important to remember that humans and chimpanzees share upwards of 98% of their DNA. Nevertheless, scientists believe that there are some critical similarities and differences between these two strains that could prove useful in the fight for a vaccine.
COVID-19 is a respiratory illness, primarily causing permanent damage to the lungs similar to SARS CoV. The two respiratory diseases have many structural similarities being in the same family, coronavirus. According to the Centers for Disease Control, SARS CoV caused 8,098 cases and had a 15% mortality rate (from 2002-2004), while COVID-19 has a much greater 4.37 million cases and an estimated 3.4% mortality rate (Dec. 2019 - Present). This increased infection rate has caused COVID-19 to become the pandemic it’s grown to today.
Doctor Peter Hotez from the National School of Tropical Medicine believes that it’s vital that we find a vaccine as soon as possible to prevent further harm but the traditional vaccine just won’t cut it. However, he acknowledges that “not many pharmaceutical companies are willing to join in as they know that there will not be a large financial return” until they see that this could become a seasonal virus. This has left smaller, but capable biotech companies to unite to form ‘Product Development Partnerships’. However, these companies face the challenge of finding a coronavirus vaccine, a task that has not been successfully executed for the past decade.
A traditional vaccine can take upwards of a decade to fully develop and successfully pass through the three-stage United States federal test. Lead scientists at the World Health Organizations say, “For over a hundred years vaccination has been affected by one of two approaches: either introducing specific antigens against which the immune system reacts directly or introducing live attenuated infectious agents that replicate within the host without causing disease synthesize the antigens that subsequently prime the immune system.” The job of these antibodies endogenously created by the body is to neutralize the threat of the pathogen; the three ways this occurs is through neutralization, opsonization, or lysis. Neutralization is the process by which the antibody binds to viruses and toxins hence deactivating them. Secondly, opsonization is the process by which antibodies bind to antigens and make several pathogens stick together. This makes it easier for phagocytes to find and engulf the pathogen. A phagocyte is a type of white blood cell, used to engulf pathogens and destroy them with certain enzymes. The final process is lysis, where antibodies activate a complementary system to puncture the pathogen, resulting in its deactivation.
However, the problem with traditional vaccines, almost always, is the timeline. As the COVID-19 Pandemic rages, it is not feasible to allow the production of the vaccine to take years to develop. Dr. Evan Rachlin and Micheal Watson from Moderna Inc., a Cambridge based biotechnology company, point out that, “The target pathogen/antigen are grown in dedicated cell-cultures and/or fermentation-based production before being extracted, killed, separated and purified. This involves a long, complex, and costly process.” They continue to elaborate that traditional vaccines “often demonstrate efficacy empirically” (i.e. without knowing why they work.), two major flaws. This led companies like Moderna and pharmaceutical giant Pfizer to use the previously failed method of Nucleic Acid Vaccines, a new approach but the same effect.
The theory behind the Nucleic Acid Vaccines is that they will deliver a certain genetic sequence (i.e. a series of nitrogenous bases) into the body, which codes for the set of proteins that the pathogen carries. There are two types of nucleic acid vaccines, including DNA and (m)RNA vaccines. Both of these vaccines work in a very similar manner, as they both intend to create a small amount of the antigen inside the body so that the body can endogenously create antibodies. However, as Rachlin and Watson continue, they point out the difficulties of DNA vaccines, illustrating that the strand of DNA must penetrate past two membranes, cytoplasm, and the nucleus. For this precision, advanced injective devices must be used, to inject a milligram of the DNA into the body. In addition to this, there is a risk that the DNA could become integrated with the human's natural genome. Many independent institutions including researchers from Dartmouth and Johns Hopkins University agree that this method is much more efficient and feasible, especially with the current advancements in the field of genetics. Moderna and Pfizer believe that their usage of mRNA vaccines will be the most optimal and beneficial to the world.
In Moderna’s ten-page report on the mRNA vaccine, it points to several key distinctions from the traditional and DNA vaccines. Firstly, there is no risk of DNA integration as the mRNA will not need to penetrate beyond the cytoplasm; this is unlike the DNA vaccine which needed to penetrate the nucleus to be effective. Since the vaccine does not need to reach the nucleus of cells, no special delivery device will be necessary, decreasing the cost. Also, the vaccine can be injected at a much smaller scale, μg v.s. Mg, or at a 1000 time smaller quantity than the DNA vaccine. Moderna strongly believes that this technology can be implemented far beyond the pandemic at hand. The RNA technology is a standard one for all viruses and is a fraction of the cost of traditional vaccines (150,000,000 to 1,000,000,000 USD).
The future of the mRNA vaccine is still uncertain, as the Moderna vaccine remains at phase two of three federal tests. However, the future looks bright on nucleic acid vaccines, as a contemporary solution for global help crises. Officials at Pfizer say, “mRNA vaccines potentially offer greater flexibility and quicker development timelines than traditional vaccines development [something we must take forward]”