A group of researchers successfully infected mice models with SARS-CoV-2, the virus of COVID-19. This would substantially affect drug and vaccine development in terms of research speed.
The successful infection of SARS-CoV-2 in mice models was led by the Washington University of Medicine in St. Louis (WUSTL), a private research university in the US. Their findings revealed the fruitful replication of COVID-19 in laboratory mice. This could allow biomedical scientists and other research groups to study the disease in mice, which would speed up research in treatment and vaccine. The viability of mice could widen the testing platforms for novel drugs. The results of the study were published in the journal Cell.
Why Animals are Used in Developing Vaccines
When the first vaccine was created, scientists around the world realized that some diseases could be prevented by drugs, even if there is no treatment available. This resulted in a new classification of illnesses called vaccine-preventable diseases, which include rabies, measles, tetanus, mumps, and polio. The majority of these diseases are caused by viruses – pathogens difficult to be drafted for a specific treatment. Usually, viral infections can only be managed or assisted by palliative care.
According to the US Food and Drug Administration, a federal agency, animals are sometimes utilized to develop medical devices and products. The main role of animal models is for testing purposes to determine safety and efficacy. For drugs, scientists tend to focus on the nature, chemistry, and effects of chemicals in animal tests. Some of the measures they examine are the absorption rate of biologics into the blood, the chemical breakdown in the body, the toxicity level of the chemicals, the breakdown of components, and the elimination of the chemicals from the body. Success in these measures is required to progress a drug candidate to human clinical trials.
In vaccine development, bacteria and viruses can be grown in the laboratory provided the synthetic environment has everything the microbes needed. However, in many situations, additional nutrients are not replicable in laboratories. Those nutrients can only be derived from blood and serum products of animals. And to make things complicated, viruses normally grow in living cells. Thus, viral vaccines are typically produced in living host cells.
Because ethical rules apply in medical tests, experiments involving pathogens disallow human models unless a prototype drug passed preclinical trials. This is why animal models are demanded by treatments and vaccines for viral infections. One way to make a virus viable in an animal is to alter certain things, usually within the animal, to permit a viral infection. Through studies, scientists can determine how the virus works without exposing a person to the disease.
COVID-19 Infection in Mice Models Accomplished
At WUSTL, researchers successfully infected mice models with SARS-CoV-2. This would open new avenues for global research on COVID-19 treatments and vaccines. Scientists across the globe could now study the virus and its mechanisms more closely with the help of mice. The success would also speed up the ongoing vaccine development the world sorely needs.
"There's been a huge push to develop vaccines and therapeutics as quickly as possible, and since animal models have been limited, these investigational drugs and vaccines have been put directly into humans, and many of them haven't panned out. Mice are useful because you can study a large number of them and observe the course of the disease and the immune response in a way that is hard to do in people. It would be more cost-effective and efficient and safer for people if we could get more information about how these potential drugs and vaccines work and how effective they are before we move to more challenging non-human primate and ultimately human studies," explained Dr. Michael S. Diamond, a senior author of the study and professor of medicine at WUSTL.
In the study, researchers noted that mice could not be infected by SARS-CoV-2. Previous studies suggested that the virus latches on a protein known as angiotensin-converting enzyme-2 or ACE2. This protein could be found on the surface of cells residing in the respiratory tract. While mice possessed ACE2, the animals have a different version of it that the virus could not recognize. Hence, the animals could never be harmed by the pathogen.
Back in the time of severe acute respiratory syndrome or SARS, research found that SARS-CoV-1 infects the same protein in humans. There was research as well that produced genetically modified mice with human ACE2 protein, but the mice colonies were shut down when SARS was eliminated. So, the team decided to recreate the same mice colonies by introducing a gene for human ACE2 into an adenovirus, which causes mild respiratory symptoms.
The team removed all genes used by adenovirus to replicate. This enabled the virus to attack and infect host cells, yet it was unable to replicate. The altered adenovirus was administered to mice models. A few days later, the mice generated human ACE2 that made them susceptible to COVID-19.
After five days, SARS-CoV-2 was introduced into the noses of mice. Researchers observed any symptom that the animals would develop. The COVID-19 virus spread quickly in the respiratory tract of infected mice. Virus levels were high and pneumonia with inflammation was apparent in the animals, similar to some people with COVID-19. But the experiment in mice allowed them to gather specific insights: the virus levels were lower in the brain, heart, and spleen, which the virus could attack in humans. Although the mice lost about 10% to 15% of their body weight during the infection, the animals recovered in the end.
According to the World Health Organization (WHO) of the United Nations, the total confirmed cases of COVID-19 worldwide peaked at 7,690,708, as of June 14, 2020. Within 24 hours, 137,526 new cases were reported in six WHO regions. The total confirmed deaths were 427,630 as of the same date, while 4,281 new deaths were reported in those regions in the last 24 hours. The Americas remained with the highest confirmed cases at 3,711,768 and confirmed deaths at 199,252.
In real-world settings, studies of mice infected with SARS-CoV-2 can unravel mysteries on how the virus attack and replicate inside organs. Medical scientists can get better data on the viral mechanisms and answer some of the questions since the beginning of this pandemic. Moreover, the viability of mice opens a new platform for testing COVID-19 treatment and vaccine models. The animals can highlight a drug's efficacy, toxicity, and sensitivity, which reveals the chance of an allergic reaction. This can potentially speed up any drug candidates in preclinical trials.