A vaccine for a new disease usually takes more than ten years to be ready to administer to people. In the case of Ebola, which accelerated, it took five years for a candidate vaccine to enter clinical trials. Vaccine development has progressed exceptionally rapidly since January, when the causative agent of COVID-19 was identified. The first COVID-19 vaccines were created and went through clinical trials in less than a year. This was a record and was recognized by Science like the “Advance of the year 2020”.
How was it possible even without cutting corners?
Many of the traditional steps in vaccine development were contracted. Initially, many assumptions were made in the development of an SARS-CoV-2 vaccine based on experience with other viruses. Vaccine manufacturers learned from the experience with Ebola. In many ways, the world was lucky enough to treat us to a coronavirus, as there were ongoing vaccine development plans for MERS, another coronavirus.
In addition, many new technologies and platforms were used that increased the speed of vaccine development. This contrasts with the first generation of vaccines for other diseases that used a more passive approach. I will discuss these technologies later in this chapter.
By the end of 2020, there were several vaccines that had gone through the glove of clinical trials and had received provisional approvals for use in many parts of the world. Although these vaccines were still in clinical trials, manufacturers had already begun the process to produce them in the hope that they would work. Two main vaccines showed similar efficacy (around 95%) in the prevention of the disease after two doses: a first and a booster12. Other vaccines were also shown to work slightly less effectively.
Basically, COVID-19 vaccines try to do the same. They depend on the idea of preventing the spike protein from binding to the ACE2 receptor. This is the key step in infection and, although antibodies can be formed against other viral proteins, the neutralizing antibodies we want are targeted to this interaction. The virus is also not completely helpless against antibodies: it is coated with sugars and tries to keep the crucial part of the ear covered so that antibodies cannot access it.
Traditionally, a vaccine was created from a virus that was isolated and weakened or inactivated.
The whole virus (or part of it) was inserted into the body (which produced neutralizing antibodies). This is the basis of most vaccines in use.
Within a few months of identifying SARS-CoV-2, there were vaccine candidates who used weakened viruses, dead (inactivated) viruses, or pieces of the virus to try to generate an immune response. This is notable not only for the speed with which vaccine candidates were created, but also because they represent so many different strategies.
Without entering into the debate of whether viruses live in the first place, colloquial vaccines with inactivated viruses are “killed” by chemical treatment or heat. This means that after injecting them into the body, they can trigger the immune system but cannot replicate inside the cells. Fully inactivated antivirus vaccines require an additional substance to boost the immune response. This is called an adjuvant.
On the other hand, instead of inactivating the virus, a vaccine can also consist of a weakened virus insofar as it causes only a mild infection, while losing all its disease-causing properties. Traditionally, weakened viruses were generated by repeatedly passing through cell cultures.
The safety of live inactivated and live vaccines is widely tested as they use real viruses.
Large amounts of virus are required for inactivated viruses. For weakened living viruses, we need to make sure they don’t go back to their disease-causing ancestral strains. Again, as a live virus is injected, thorough testing is needed to make sure they are safe for those with compromised immune systems.
An example of an inactivated vaccine is Covaxin, which was created in India by the National Institute of Virology of the Indian Medical Research Council and Bharat Biotech. Thousands of participants were enrolled in a phase III clinical trial in late November 2020.
Other vaccines can be made from parts of virus proteins or virus-like particles, all deficient in some key component present in an infectious virus. Some of these also require adjuvants to trigger the immune system.
Some vaccines consist of virus proteins packaged in nanoparticles and injected into the body. These viral proteins are recognized as foreign by the immune system, which begins to give an adequate response. By the end of 2020, Novavax had enrolled patients in phase III clinical trials for their version of this type of vaccine.
Another approach is based on creating a “virus-like particle” that mimics SARS-CoV-2, but has no genetic material inside. They are expected to cause an immune response in the body, but because they have no genetic material, they are not infectious. However, vaccines approved in late 2020 and most other candidate vaccines use platforms that do not require viruses or real parts, but use genetic information to get human cells to create parts of the virus. way the virus would.
These are fast and secure systems.
DNA or RNA is injected into the body, where it serves as a plane for the cellular machinery to form parts of a virus that attach to antigen-presenting cells. The immune system recognizes these parts of the virus created by cells as “alien” and makes antibodies against them. Prior to this pandemic, there was limited experience working with these systems, although some of these platforms were reasonably successful with cancer and other molecular diseases.
Some companies use the route of a DNA vaccine with garland-shaped genetic material. Getting DNA into the cells has been a bit of a problem. Therefore, a technique called electroporation is used, which uses electricity to briefly create holes in the cell membrane. Once inside the cell, DNA is transcribed into RNA which translates into the coronavirus ear protein which, hopefully, can cause people to generate a strong immune response.
But by the end of 2020, the vaccines that had generated the most excitement used RNA.
An RNA vaccine completely skips the first steps of a DNA vaccine and induces potent immunity. Once inside the cell, it translates directly into the spike protein that the host cell uses to generate immune responses.
In late November, two major candidate vaccines created by Pfizer and BioNTech and Moderna using RNA technology were shown to be effective after two doses. In December, these candidates were the first two major vaccines approved in the world. The widespread use of mRNA vaccines may indicate a paradigm shift in the way attempts are made to prevent the spread of infectious diseases.
Why are only the first approved RNA vaccines now available? After all, they could have helped us fight other infectious diseases in the past. Three recent technical advances make these vaccines possible. First, RNA is unstable and difficult to access cells. But by incorporating it into molecules known as lipid nanoparticles, delivery and stability have been improved. Second, “foreign” RNA can elicit an immune response (rather than the protein it helps the body produce). But if RNA is chemically made from synthetic nucleosides, the immune system does not react against it. Third, RNA is “read” by host cells to make viral proteins. But before it was modified and stable, it didn’t read well. The proverbial stars lined up shortly before the COVID-19 pandemic.
However, RNA vaccines are not without disadvantages. RNA is less stable than many other biological molecules.
Enzymes that can degrade RNA are ubiquitous. Even with chemical changes that improve stability, the Pfizer vaccine should be kept at -70 ° C. The Moderna vaccine is more stable and can be kept in a normal freezer at -20 ° C for six months.
The ability to produce and distribute hundreds of millions of doses of RNA vaccines during an active pandemic remains a challenge. But the good news is that by the end of 2020, clinical trials and preliminary observations after weeks of wider deployment indicated that both RNA-approved vaccines were generally well tolerated. Some adverse effects such as injection site pain, fatigue, headache, or mild fever had been reported, but there were no general safety concerns.
The last class of vaccines I want to talk about contains a DNA plan inserted into the shell of a harmless virus (usually an adenovirus vector). This is quite ingenious, as it uses a defective virus to send a message that will generate antibodies against SARS-CoV-2. These defective viruses generate immune responses, or are too weak to cause disease or lack the components needed to reproduce completely.
By 2020, AstraZeneca, along with Oxford University, and Johnson & Johnson were two companies that had enrolled thousands of participants in vaccine trials using adenovirus vectors. By the end of 2020, AstraZeneca’s vaccine candidate had shown promising initial results and was ready for approval in 2021.
Extracted with permission from Covid-19: separating fact from fiction, Anirban Mahapatra, Penguin Books.