As we enter into the third month of COVID-19, a lot of us are wondering when a vaccine will be developed to prevent this from ever happening again. Unfortunately the answer is not a simple one. The process of developing a vaccine can take a long time and often is very costly for the manufacturers. In this article we’ll explore the process of vaccine development and what it takes to get cleared for market consumption. Vaccine development occurs in stages, each of which take a certain amount of time, to create something that has the desired effect and is safe for the entire population (including children, people at risk, and the elderly) to consume.
Step 1: Generation of an Antigen
An antigen is a toxin or other foreign substance which induces an immune response in the body, especially the production of antibodies. During this step scientists must identify and create a relevant antigen which will induce an immune response. In order to do this, there are three basic research pathways to take when creating an antigen:
- Use of a pathogenic agent, but attenuated, inactivated or genetically modified
- Using components of the virus to induce a specific immune response. This is especially important in preventing infection
- Creation of a pseudovirus, which looks like the normal virus but lacks the actual genetic material
During this step it is essential to understand any mutations the virus may have undergone since its initial discovery. Characteristically, viruses mutate frequently, and Coronavirus is no exception – it actually mutates rapidly as well. For example, the COVID-19 strain that is currently in Italy has been found to have mutated from the original virus found in Wuhan, China (where the virus is believed to have originated from). Once the antigen has been created, different immunization processes must be undertaken, beginning with animal testing. This is done in part to determine specific immune parameters, i.e. whether there is any production of neutralizing antibodies.
Step 2: Release and Isolation
The second step is to release the antigen from the cells and isolate it from the material used for growth (i.e. cell culture). Proteins and other parts of the material may still be present and must be separated in the next step. The goal of this stage is to release the virus from the cells where it is being contained.
In order to replicate itself, the virus needs a host – in this case the host is the cell. The virus enters into a cell, and stops either in the cytoplasm of the cell (if it is a RNA virus, such as COVID-19) or it travels to the nucleus (if it's a DNA virus). Settled in their new locations, this is where the virus replicates.
During vaccine development the host cell that is used is often not a human cell (due to cost, availability, etc.). This is why the antigen, and not the complete cell, is used in vaccines as the non-human cell can cause health problems in humans.In vaccines we use to have only the antigen, not the complete cell, because this can cause health problems to patients due to media are usually not human cells.
Step 3: Purification
The third step is the purification of the oxygen medium where the cells grow. The goal is to purify the antigen enough to remove anything that may be harmful to the possible patient.
Step 4: Strengthening
This step is being used more frequently these days as it was discovered that the addition of co-helpers improved the immune response in patients. Co-helpers are very often used when a vaccine has a low concentration of the antigen, making it possible for the patient's body to generate enough antibodies as an automatic immune response without the patient ever experiencing side effects of the virus. During this stage stabilizers and / or preservatives are added as well which extends the useful life of the vaccine.
When people become infected with a virus, the main problem is the patient's immune response. A common cold has a fast and controlled immune response, but that is not the case with many other viruses. If the body’s response is not controlled properly an overproduction of cytokines is generated which inflames the body and can cause pneumonia or even organ failure.
Step 5: Clinical Trials
When we reach this stage, it is ready to start the clinical and preclinical tests. Up to this point the only thing we’ve actually done is to colonize the host (cell) with our antigen to assess the patient's immune response. Now it's about seeing its effectiveness and safety. Safety in terms of the patient's immune reaction and efficacy so that in a situation where the patient faces the virus, his body reacts as expected. Also at this point it is essential to know when the immunity lasts.
So, now that we know what it takes to discover a new vaccine and get it on the market - where exactly do we stand today with finding one for COVID-19? Laboratories around the world work together to systematically collect samples of circulating influenza viruses and send them to the WHO (World Health Organization) Collaborating Centers for Flu Research and Reference to be analyzed. If a new strain of the influenza virus is identified and isolated, it takes five to six months for the first batches of the approved vaccine to be ready. The first stage of production of a pandemic vaccine begins when one of these centers detects a new strain of the virus that differs considerably from the current circulating strains (i.e. the Coronavirus). Thanks to this collaborative effort, the complete genetic sequence of the COVID-19 virus has been discovered in just a few short weeks.
Simultaneously, the WHO prepares standardized substances and provides them to manufacturers so that they can achieve the drug performance they are looking for and also package the correct doses of the vaccine. This stage takes at least three months and can often represent a bottleneck for manufacturers. Today, around thirty-five companies and academic institutions worldwide are competing to create a COVID-19 vaccine, four of which have reported that animal testing has already begun.
The first of these, produced by Boston-based biotech firm Moderna, Inc., will enter human trials very soon but no official date has been released. Moderna was able to piggyback on their previous work for MERS (Middle East Respiratory Syndrome) at the U.S. National Institute of Allergy and Infectious Diseases, in Bethesda, Maryland.
Novavax, based in Maryland, has studied coronaviruses in more detail, since they have also worked on vaccines for SARS (Severe Acute Respiratory Syndrom) in China in 2002 - 2004, and MERS which started in Saudi Arabia in 2012. In both cases the work on the vaccines was started but then shelved when the outbreaks were contained. Novavax has now repurposed those vaccines for SARS-CoV-2 which means most of their work is already done. It's been discovered that SARS-CoV-2 shares between 80% and 90% of its genetic material with the virus that caused SARS. Both viruses consist of a strip of ribonucleic acid (RNA) inside a spherical protein capsule that is covered in spikes. The spikes adhere to the receptors on the surface of the cells that line the human lung, the same type of receptor in both cases, allowing the virus to enter the cell. Once inside it hijacks the cell's reproductive machinery to produce more copies of itself before leaving the cell again and killing it in the process.
So, as you can see, coming up with a solution in the form of a vaccine is not an easy process. But there is hope and it looks like we are well on our way toward discovering a vaccine for this deadly virus.
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