Let’s demystify vaccine design

From research to design, here’s the process that goes into creating vaccines

Vaccines are among the safest medical products in the world due to rigorous trials tracking their safety and effectiveness. Recently, we have seen an unprecedented global effort in the search for a vaccine to the Covid-19 virus.

As the Covid-19 virus continues to spread, researchers are making significant progress in the search for viable vaccines. As the scientific community around the world works towards developing a vaccine and vaccine debates circle, the process that happens behind the scenes can seem elusive to anyone without a scientific background. To demystify vaccines, here’s what happens from research to design.

The first step in the process for finding a vaccine which works begins – as most scientific endeavours do – with basic research. Trinity is one of the third-level institutions which has had an influence on vaccine development. The Trinity Covid-19 Immunology Project received €2.4 million in funding from AIB earlier this year and one of the main areas of Covid-19 that they are focusing on is informing vaccine design. Although Trinity will not be designing them, the research being conducted will provide novel expertise to pharmaceutical companies, such as how to better induce memory responses in vaccines. Since the search began at the beginning of this year several pharmaceutical companies have seen their products reach the final stages of clinical trials.

There are four stages one must go through before approval. These are preclinical testing, then safety trials, expanded trials, and finally efficacy trials. Scientists test a new vaccine on cells and then give it to animals such as mice or monkeys to see if it produces an immune response. Then it is given to a small test group to test safety and dosage.

Once it is confirmed that the vaccine stimulates an immune response, scientists can then administer the vaccine to hundreds of people within different demographics to see if it is still effective in different subsets of the population. 

Significant progress has been made and what can often take years or decades has been achieved in a matter of months.”

The third and final stage is the efficacy trial. This is when the vaccine is given to thousands of people to see how many people become infected, compared with the placebo. This is crucial to see if the vaccine works, and can often reveal rare adverse reactions that might have been missed in earlier studies. Significant progress has been made and what can often take years or decades has been achieved in a matter of months.

A number of these vaccines have reached Phase 3 of the trials, with some even approved for limited use.”

A number of these vaccines have reached Phase 3 of the trials, with some even approved for limited use. There are different types of vaccines; one type which has been successful is a genetic vaccine being developed by US pharmaceutical giant, Moderna. This type delivers one or more of the coronavirus’s own genes into our cells to provoke an immune response. It uses a messenger RNA (mRNA) to produce viral proteins in the body. The vaccine yielded promising results in the preclinical testing, showing that it produces enough antibodies in monkeys to protect them from the coronavirus. 

The vaccine has progressed into Phase 3 testing and the final trial has recruited over 30,000 healthy volunteers from all over the United States. It needs to be seen how many of their volunteers become sick with the virus before determining how safe and effective it is. It will be the end of 2020 or early 2021 before sufficient data can be collected to determine its efficacy.

Companies are testing out just about every technology they can for a Covid-19 vaccine. Some of the experimental vaccines are based on old designs which could be repurposed for Covid-19. One such vaccine is the BCG vaccine. It was developed in the early 1900s as a protection against tuberculosis and works by boosting nonspecific immunity against other viruses, so it might do the same thing for Covid-19. The Murdoch Children’s Research Institute in Australia is currently conducting a Phase 3 trial to see if the vaccine partly protects against the coronavirus.

New outbreaks in recent years such as ebola and pandemic flu strains have spurred vaccine makers to search for ways to speed up the development process without compromising safety. Now, they’re putting these ideas into practice. There are several ways to accelerate vaccine development; one of them is to combine phases. For example, some coronavirus vaccines are now in a mix of Phase 1 and 2 trials, in which they are tested for the first time on hundreds of people rather than a small test group. 

Both China and Russia have taken it one step further and approved vaccines without waiting for the results of Phase 3 trials. China has four vaccines which are approved for limited use. One of them is called a viral vector vaccine. This technology is relatively new, and uses a virus engineered to carry coronavirus genes. There are no vaccines in the market based on this type of technology. The Chinese company CanSino Biologics made their product from an adenovirus (a harmless cold virus) carrying a coronavirus gene. 

It is the same technology which is being used by AstraZeneca who are working in conjunction with Oxford University. Trinity alum Dr Adrian Hill is the Director of the Jenner Institute, a group within the university which develops vaccines and carries out clinical trials for diseases. Their vaccine has reached the final stages of clinical trials but was halted due to one of the participants having an adverse reaction. Oxford University confirmed that the trial would continue, stating that: “In large trials such as this, it is expected that some participants will become unwell and every case must be carefully evaluated to ensure careful assessment of safety”.

However, unlike the EU and US, China and Russia are taking a dangerous step by approving the distribution of vaccines without the results of Phase 3 trials. “This would never be acceptable in Europe, the United States or in any other developed country around the world,” according to Professor Kingston Mills, Head of the Centre for the Study of Immunology at Trinity Biomedical Sciences Institute. Unlike experimental drugs given to the sick, vaccines are intended to be given to masses of healthy people. “If you’re giving it to children, who are unlikely to die from Covid-19, you cannot risk giving something to a child or infant who is otherwise healthy, if there is any risk that it will cause a side effect,” says Dr Mills. Putting in safeguards slows the development of vaccines but is not something that can be expedited.

So when will we see a safe and effective vaccine against Sars-CoV-2? It is impossible to tell before the results of the efficacy trials when a vaccine could be available. There are 11 vaccines in final trials so we might know the outcome of a couple of these in the next 2–3 months. Pending positive results, “we could see one in production early next year and starting to be rolled out in February or March,” says Professor Mills.

How important will it be for all of us to take the vaccine when there’s one available? “Err.. VERY!” wrote Dr Luke O’Neill, professor of biochemistry at Trinity, and world class science communicator. Professor Mills said: “Covid-19 can kill whether you’re 20 or 80 years of age. The virus can damage the lungs, heart and brain, which increases the risk of long-term health problems.” Even though most younger people make a full recovery, by being vaccinated you’re not only protected from it yourself, but you also won’t be able to pass the infection onto other people.

However, for herd immunity to work, a large proportion of the population needs to be vaccinated. There is no point in having an effective vaccine if the majority of people don’t take it. “It’s up to young people to come out and take the vaccine.”