|What are the steps to follow in order to have ready the vaccine against Covid19?|
|Question Date: 2020-09-11|
Great question. Everyone wants a safe, effective vaccine. More specifically, they want a vaccine that is safe and effective for humans. The only way to know if a vaccine meets those criteria is to test it on humans. Researchers need to follow a lot of guidelines and get permission for those tests.
One problem is that the testing method that is most scientifically valid may not be the most ethical. It might not even be legal. The safest way to proceed will slow down the testing. This question gives us a way to look at how to design a valid (fair) test, but to also show some of the realities of developing a vaccine in the middle of a pandemic.
The most scientifically valid test would be to start by randomly choosing a large sample from everybody on Earth for testing. Obviously that’s not going to happen. The sample will probably be healthy adults from whatever country is doing the testing. That will give researchers an idea about how healthy adults from their country will respond to the vaccine. They have to hope it works in a similar way on, say, sick children or elderly people.
By the way, when scientists say “random” they don’t mean sloppy. They mean that every individual has the same chance of being chosen.
Testing a new vaccine or treatment usually involves a double-blind study where people are randomly assigned to either get the treatment or to get a placebo that is like the treatment as much as possible, but does not contain the actual drug or vaccine. The people don’t know which they are getting. The people collecting the data don’t know which group each person is in. This is important because people who get a placebo often report that they feel better. If they know the potential side effects of the drug, they may even get side effects of the drug (even though they only got the placebo). Also it avoids bias by the people gathering the data. Even when people are trying not to cheat, they may influence the data without being aware of it. For example, they might expect a person’s blood pressure to have decreased, so they might think a high reading is a mistake and try again.
Why even have a control group that gets the placebo? If you don’t have anything to compare the treatment group to, how will you know whether the treatment made a difference? To know whether the vaccine protected people, or gave them a side effect, you have to compare them to people who are as alike them as possible, except for the vaccine itself.
So let’s say you are ready to put people in 2 groups by flipping a coin. Then you will give half the vaccine and the other half an injection that is just saline (the liquid that the vaccine would be in). To see whether it works, you have to expose them to the virus. The quickest way to do that is just swab them with the virus. But is that ethical? Remember that half of the people got a placebo, not a vaccine. To avoid that problem, you can turn everyone loose to live their lives and check back to see who is sick. It might take months before they even get exposed. Maybe they never will be. So a few months later you test both groups for the disease. If a lot more people in the control group than the vaccine group got the disease, you have evidence that the vaccine is effective. But is it safe?
Let’s say that both groups had about the same number of health problems during your study. Remember that people get headaches, sore muscles or even serious problems for lots of reasons. You’re just interested in whether the treatment group had more problems than the control group. Let’s assume that there were no differences or the differences were minor, like more sore arms or nausea that lasted a few hours. Is it safe? Maybe. Maybe it takes months for the side effect to show up. That will delay your results a while. You don’t know how long to wait for side effects. You have to guess based on past studies.
Different people have different responses. Maybe 1 out of 1,000 people will die if they take the vaccine. If you tested 100 people in your study, you may not have included one of these people. So you may need to test a lot of people. You don’t know if there are rare people who will have a bad reaction or how rare those people will be. Do you start off testing on 10,000 people? What if it turns out to cause major problems for 30% of the people. That’s bad. So what about starting with a small group, and if all goes well for a few months, doing a bigger study? That sound good, but people are impatiently waiting for a vaccine, and some of them are dying.
In some movies, the brave crew of scientists finds a person who is immune (or something) and the next scene shows everyone being saved. Unfortunately, this may have given many people false expectations. Vaccines are amazing when they are safe and effective. They allowed public health workers to stop terrible diseases like smallpox and polio. They prevent many deadly diseases. Making sure all vaccines are safe and effective is important for protecting people and also for making sure that people feel safe enough to take them.
If you want to help defeat diseases, you may be interested in a career in public health, medicine, or microbiology.
Thanks for asking.
Vaccine development can be a lengthy and complicated process.
The first step to developing a vaccine is actually determining what the vaccine is going to be. Generally vaccines expose you to an antigen, which is some part of the virus or bacteria that will induce your body to mount an immune response. Vaccines may expose you to the antigen by simply exposing you to the entire virus in a weakened or killed state, or by exposing you to a single piece of the virus, such as a protein that the virus uses to enter cells. Once a research team has determined what antigen to use, they begin pre-clinical trials. These are either done on human cells cultures, which are human cell types grown in petri dishes, or in animals. These pre-clinical trials are used to determine if there are any adverse effects the vaccine has before moving to human trials, and also to determine if the antigen they have chosen actually induces an immune response in the test subjects.
In the US, once these pre-clinical trials are completed, researchers apply to the Food and Drug Administration to begin testing the new vaccine in humans. They start with phase 1 trials, where a small group of human volunteers are exposed to the vaccine to test for side effects and also the induced immune response when given to actual people. If the phase 1 trials show that the vaccine is safe and produces an immune response, which is referred to as "immunogenic", the vaccine moves on to phase 2 trials.
During Phase 2 trials, a larger test group is given the vaccine, again testing for safety and immune response. Phase 2 trials are also often when tests regarding dosage, vaccine delivery, and vaccination schedule are determined. Finally, a vaccine that is demonstrated to be safe and immunogenic moves on to phase 3 trials.
Phase 3 trials involve an even larger test group. Phase 3 trials are important for catching extremely rare side effects, such as those that might occur in 1 in 10,000 instances, by testing on 10s of thousands of volunteers. Phase 3 trials are also when the vaccine's efficacy is tested.
While the vaccine may induce an immune response according to phase 1 and 2 trials, phase 3 trials help scientists determine if the vaccine actually helps in preventing people from getting the disease. Of course at every step along the way, control groups and safety are vital.
Vaccine trials may be suspended or stopped for a variety of reasons. In fact, just recently a phase 3 trial for a covid-19 vaccine was suspended due to a single person presenting neurological symptoms. Further testing must be done to determine if the Covid-19 vaccine caused the symptoms in the person before the trial may proceed. Once a phase 3 trial is completed and the vaccine has been demonstrated to be safe and effective in a large population, it is approved for use in the general population.
Thanks to the incredible effort of research labs and scientists around the world, and large amounts of funding from many different governments, there are over 90 candidate vaccines for Covid-19 already, and many are already moving into human trials, with some in Phase 3 trials as mentioned above. This is an unprecedented pace for vaccine development, but it's also important that these trials take place so the vaccine that is eventually developed has been proven to be safe and helpful in slowing or stopping the spread of Covid-19.
In the United States, vaccines are regulated by the Food and Drug Administration. A new vaccine must pass a series of clinical trials to be approved by the FDA. You can find more details on the drug development process on the FDA Website. .
In general, some level of animal experiments are needed to show that a vaccine is worth further investigations in humans. Those experiments are the development and pre-clinical researches stages. In the development stages, there are experiments needed to show that a vaccine can induce an immune response against the pathogen in question. In the pre-clinical research stage, there are experiments to show that the vaccine will not cause harm in animals.
Once the pre-clinical research yields a positive outcome, the vaccine can enter the clinical research. In Phase 1 of the clinical research, the vaccine is tested on a handful of volunteers to show that it will not harm a human being. In Phase 2, experiments will determine how much doses the vaccine is needed to induce a satisfactory immune response in a larger group of volunteers than Phase 1. In Phase 3, the vaccine is tested on an even larger group to confirm the findings in Phase 1 and Phase 2.
Once the vaccine passes Phase 3, the pharmaceutical company can apply to the FDA for approval. Since COVID-19 is an extraordinary situation, some vaccines are approved for limited use before the full approval. If the vaccine is approved, it can be released for use in treatment.
At the time of writing (September 11, 2020), 3 vaccines have been approved for limited use. The New York Times has a tracker for the status of vaccine development .
There are reports of reinfection of recovered patients and how strong the immunological memory SARS-CoV-2 and its vaccines can induce remains unclear at the time of writing. The lack of long-lasting antibodies will be a major challenge to the vaccine development. The journey will be arduous.
The steps for developing a vaccine against any virus are very similar. First, scientists have to identify the virus and learn basic information about it - they'll want to figure out how the virus enters the body and attacks cells, for example. They will also sequence its genetic material and predict what kinds of proteins it makes. Next, they will decide what kind of strategy will be best for developing immunity against the virus.
Some vaccines work by injecting "attenuated" virus particles into patients - this means that the virus has been killed or weakened so that it can't harm people, but will still generate a strong immune response. Other vaccines work by injecting small pieces of the virus, like proteins that are expressed on the virus's surface. This trains the immune system to recognize the virus before it ever sees it.
Once they have developed their strategy, the team of scientists (and there are several teams working on different strategies across the country) will try out their vaccine on animals to make sure its safe for people and that it can prevent infection. If the vaccine does not lead to harmful side effects in animals, the researchers can then move into clinical trials - this is the first step where the vaccine will be tried out in people.
Clinical trials start small to double check that no side effects occur, and then more people are tested (usually those at higher risk like nurses and doctors) to determine if the vaccine is effective at keeping people healthy. If the vaccine is proven safe and effective, it can then be manufactured in large quantities and distributed to everyone. This entire process can take a year or more from start to finish, but is often streamlined during a crisis because funds and resources are directed towards finding a vaccine more quickly.
In addition to these challenges, researchers will want to develop vaccines that will be effective even if the virus mutates. Because viruses have a short life span, they can adapt to new threats very rapidly. When scientists make vaccines to seasonal diseases like the flu, for example, they often have to predict the most common 'version' of the virus that will be circulating during the year. This is another reason why it can take a while to produce effective vaccines.
Here is a link that provides a good summary of the steps needed for developing a SARS-CoV2 vaccine: steps for vaccine development.
If only it were as simple as a series of steps.
What you need to make a vaccine is something that triggers the patient's immune system to respond as if it were exposed to the virus itself. Often, this means creating a version of the virus that isn't harmful.
In the case of coronaviruses, however, many coronaviruses evolve very quickly, so quickly that vaccines aren't useful because, by the time you've created a vaccine, the virus has changed so much that you would need a different vaccine. As an example, a significant fraction (about one quarter, I believe) of common cold viruses are coronaviruses, and we don't have a vaccine for the common cold.
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