While basic research using animals gave scientists a greater understanding of the Covid-19 virus, such as its structure and genetic composition, and how best to design an effective vaccine, animals have also been essential in the later stages of the development process as well, writes Becky Jones.
As the Covid-19 pandemic surged in 2020, the world turned its focus to the hope of a vaccine. Now, several successful vaccines have been developed, approved for use and rolled out, both thanks to the combined efforts of the biomedical community, and the essential role of animals at more than one stage of the process.
And while some question how Covid-19 vaccines managed to be developed so quickly, when other vaccines take decades, and ask if some stages of testing were skipped, the answer is that the unprecedented global effort and vast investment to find a cure has simply sped up the normal process. Innovative methods have been used, but the vaccines have gone through every regulatory stage, including those safety stages that require the use of animals.
All of the successful Covid-19 vaccine candidates that are in the process of being approved across Europe and beyond relied on animal studies during the early stages of basic research, all the way through to preclinical testing where animals are used to prove a vaccine’s safety.
Animal testing is critical to ensure that the vaccine does not end up making the infection worse, or even fatal.
Vaccine development with animals
Once researchers believe they may have a viable vaccine, strict regulations require that it is not tested on humans until preclinical trials are conducted to ensure the vaccine is safe and effective. These are first developed using cells and tissues in the lab (in vitro), and the best candidates from these in vitro tests are then studied in more detail using animals.
Preclinical trials are used to understand the toxicity of the vaccine, in other words how well it does its job without harming any other tissues. Testing in animals also helps researchers understand the type of immune response that will be generated in a vaccine, and whether that might be enough to protect the individual from developing the disease, known as the efficacy.
Animal testing is critical to ensure that the vaccine does not end up making the infection worse, or even fatal. A relevant species is used to test these trial vaccines depending on the disease in question, but most commonly the preclinical testing will involve mice, rats or monkeys. Following this, the vaccine moves on to its first human trials - known as Phase I of a clinical trial - where a small number of healthy, human volunteers are vaccinated to see if the vaccine acts in the same way in humans.
How do vaccines work?
Vaccines help teach the body fight off an infection, called a targeted immune response, to something which it has never come into contact with before. There are three types of vaccines against viruses, which all use a slightly different method of training the body’s immune response to attack and prevent the individual from becoming ill. The vaccine contains a small portion of the virus, inactivated so as not to cause harm, or a small part of a similar virus which will help invoke an immune response, but does not itself cause illness. The virus is injected into either cells or chicken eggs to allow it to reproduce many copies, which are then used in the vaccine alongside adjuvants which boost the body’s immune response, meaning a small amount of vaccine can generate an appropriate attack if it comes into contact with the virus. For the first time with Covid-19, a new vaccine technology has been used. The Pfizer/BioNTech vaccine and the Moderna vaccine comprise a small amount of genetic material (mRNA) from the virus which when injected into the body is taken up by the host cells and allows them to reproduce the protein themselves. In this case, the genetic material will make the cells produce the spike protein of SARS-CoV-2, which allows the virus to attach itself onto the cells of the body and infect them. By teaching the body how to make copies of a part of the virus, there is no need to first produce copies of the virus in chicken eggs or cells, which can speed up the vaccination production process.
Testing the leading Covid-19 vaccines
The recently approved US/German Pfizer/BioNTech vaccine underwent preclinical testing using mice, testing different doses of vaccine on groups of eight mice per dose. Testing in mice was initially to see if the vaccine would produce any kind of immune response, and these mice were then monitored closely for up to 14 days to see if this was the case.
However, infected mice are not usually affected by the coronavirus, and so further testing in monkeys is necessary to see if the vaccine can actually protect the individual from the potentially devastating effects of an infection. In this case, 12 rhesus macaques were used to test the vaccine, and after exposure to the virus all of the monkeys which had received the vaccine were protected from infection. The Moderna vaccine was examined in much the same way, this time using mice and 24 rhesus macaques.
During the Covid-19 pandemic and due to the global need to develop vaccines and drugs against the virus as quickly as possible, the European Medicines Agency stated that while it was still ‘necessary to obtain data in animals and to characterise the immune response induced by a SARS-CoV-2 vaccine candidate’ these efficacy trials did not need to take place before the vaccine went to the next stage of clinical testing.
Due to the urgency of the situation, candidates for the Covid-19 vaccine were given approval to simultaneously test their vaccines on animals while they were conducting Phase 1 trials on humans. Only the initial safety tests for each vaccine were necessary before they could go forward, and further efficacy tests with animals were conducted at the same time as Phase 1 trials in humans.
As Dr William Moss, executive director for the International Vaccine Access Center at Johns Hopkins University, USA, told Associated Press.
“They overlapped preclinical studies with the early phases of the trials. In fact one of the reasons we are even talking about vaccines now just 10 months later is that some of the phases in which vaccine development normally occurs were overlapped rather than done sequentially.”
The UK Oxford vaccine works in a more traditional way, using a small, inactivated portion of a coronavirus similar to the one that causes Covid-19. The researchers also used mice and rhesus macaque monkeys in a very similar manner to the Pfizer/BioNTech and Moderna vaccines. This meant first assessing the ability of the vaccine to produce an appropriate immune response, and then studying to see if the vaccine protected the animals from infection, ensuring that the vaccine does not end up making the infection worse. In both cases, animals were followed up for at least 14 days post exposure to the virus, and then longer term to see how long the vaccine might be effective for.
The incredible speed with which a vaccine for Covid-19 has been developed is a testament to the hard work, funding, and urgency that the pandemic has inspired across all disciplines. This accelerated research process will likely have changed the way future vaccines are developed, but it is important to note that the success we see today is thanks in part to a small, but significant amount of animal research.
Picture acknowledgement: NC3Rs UK (rhesus macaques)