There’s lots of talk about vaccines as the best way to end the pandemic – a safe and effective intervention to safely establish immunity to SARS-CoV-2 and allow us to get back to normal life. With an effective vaccine and global vaccination program, it may even be possible to eradicate this disease.
However, there are considerable hurdles to overcome, including the mechanics of vaccinating everyone, inducing immunity to the virus in over 60% of the world’s population, and shortening the five years it usually takes. To understand what we’re up against, it’s essential to understand what a vaccine is, what types of vaccines there are and what progress we’ve made so far.
How do we fight off viruses?
To be effective, a vaccine needs to mimic the virus by provoking the body’s defense responses – our immune system – after it infects the host, but before it has a chance to make us sick. The body fights the invasion by producing an army of cells and antibodies capable of neutralizing or killing the virus.
The next step of the immune response occurs during the recovery, when the body produces a second set of highly specialized cells that can identify the virus – a process called ‘immunological memory’. These memory cells and antibodies block reinfection, giving us protection against having the disease for a second time. This is what we call immunity.
Thus, a vaccine works by tricking the body’s defense system into thinking that it has encountered a virus and provokes the needed immune response and immunological memory against the virus. So when it encounters the actual virus, it will fight it off before it can make you sick.
What is immunological memory?
But like any memory, immunological memory is unreliable: Sometimes it’s short-term, and sometimes it’s lifelong. Flu vaccines, for example, are good for about six months, while a Diptheria vaccine works for roughly ten years. For measles it’s usually lifelong.
With viruses, like the flu, small genetic mutations keep changing the proteins on its surface. As a result, we have to generate a new immune response to them every year; our previous response is no longer protective. In these cases we need to get a “booster vaccine” to keep antibody levels above the protective thresholds.
How are vaccines tested?
The development of vaccines takes a long time because of extensive testing for safety and efficacy. Typically, the vaccine process includes design, production, testing in experimental animals and then testing in humans.
For safety and effectiveness, there are three phases. The first is a Phase I trial designed to test safety by administering the vaccine in different doses to healthy volunteers and monitoring for side effects. If there are no side effects, a phase II trial begins and aims to establish the effectiveness of the vaccine in a few hundred people of different ages and health statuses. Then the Phase III trial tests thousands of people and takes as long as the usual natural disease conditions. Once the vaccine goes through the three phases, it is ready for production and regulatory approval. This process usually takes about five years.
Unfortunately, we don’t have five years.
So a lot of people are working in parallel on this – probably more than for any other vaccine in history – with over 100 COVID-19 vaccines now in development, using traditional, DNA and RNA, and Bacille-Calmette-Guerin (BCG) vaccines.
Traditional vaccines are – like polio vaccines – made by either killing or weakening the virus so that it is no longer infectious but still triggers an immune response. Because of their long, trusted history, some traditional approaches are being used to develop COVID-19 vaccines, along with boosters to strengthen the response.
Other promising approaches use viral proteins to stimulate an immune response, or DNA and RNA vaccines that turn the body into a factory to produce the viral proteins. In some versions, these work by packaging SARS-CoV-2 genetic material inside of a safe virus[MOU1] , that nonetheless stimulates the immune response yet without harming the host. Another is the BCG vaccine, like that used against tuberculosis. Here, the immune system responds to the BCG and then non-specifically protects against infection from other viruses by reducing the quantity of infectious virus, thereby reducing the severity of the viral illness.
The goal, of course, is to produce the highest level of immunity with the fewest side effects. Ideally, it would also be quick to produce in large quantities, require small amounts of vaccine per dose, be cost-effective, inexpensive, require no refrigeration, and be easy to administer.
A landscape of COVID-19 candidate vaccines in clinical and pre-clinical studies has been published by the WHO, illustrating the approach, the developer, the virus target, and the current phase of development. As of May 27, 2020, this list reports 125 vaccine candidates in various stages of development.
A race against time
Among these, ten candidates vaccine are already in phase I and II clinical trials. Five of the candidates are RNA or DNA vaccines, one is a recombinant viral protein (made in the laboratory) combined with an immune booster compound, and four are inactivated vaccines. The further along in the development, the sooner we can hope to have a vaccine.
Recently, there has been hype about SARS-CoV-2 vaccine candidates with an RNA vaccine trial with promising results in 8 subjects. Also, a study in the Science magazine reported an inactivated vaccine candidate tested in mice, rats and monkeys that seems promising. There is also evidence that BCG is effective. But it is still too early to say which is the safest and most effective.
Scientists are in a race against time. Our work must be meticulous but also cooperative: We need to work together and share data, but also with strict scientific methodology and without cutting corners.
The successful vaccine must also work specifically for the novel SARS-CoV-2. If not, we can still stimulate the immune system by adding in known boosters. It also might be possible to combine strategies and create a vaccine cocktail. Another key is longevity. Otherwise, we will need to vaccinate repeatedly, as we do with the annual flu, or find a way to provoke a better immunological memory response.
It also needs to work on a large population of people of different ages and health conditions, including the elderly who need it the most. If it worked for more than 60% of the population – and was also affordable – we could end the pandemic.
In all likelihood, we will have a vaccine: With so many scientists working on this, we could conceivably have a usable result in 18 months, as we did for SARS-CoV-1.
But it could be less. We’re working on it.