April 24th 2020
It is timely, although perhaps unfortunately so, that #WorldImmunizationWeek starts today. This global public health campaign, to raise awareness and increase rates of immunization against vaccine-preventable diseases around the world takes place each year during the last week of April. The theme this year is #VaccinesWorkforAll and the campaign focuses on how vaccines–and the animals, the researchers and the individuals who develop and deliver them–are invaluable for protecting the health of everyone, everywhere.
As we face a global pandemic with COVID-19, the likes of which has never been experienced, it is timely to highlight the vital role that vaccines play in preventing diseases and the vital role that animal research has and continues to play in vaccine development, as well as in safety and efficacy studies that can prevent adverse events, including death, from occurring.
How is animal research playing a role to develop cures for COVID-19?
The animal research to inform the development of the COVID-19 vaccine began in 2002—18 years ago—with the Severe Acute Respiratory Syndrome (SARS) epidemic, with 8098 reported cases and 774 deaths reported in 17 countries. There was no vaccine for SARS during its outbreak.
Subsequent to the SARS outbreak, researchers produced a vaccine that made it to Phase I human trials, in which the safety of a new drug is tested. But the effort never progressed further, mainly due to shifting research priorities as the outbreak came to an end, says Dr. Anthony Fauci, the longtime director of the U.S. National Institute of Allergy and Infectious Diseases (NIAID).
Before moving to clinical trials in humans, the safety and efficacy of the SARS vaccine was tested in mice and rabbits (e.g., here and here). Why? Because the ethical codes adopted by many nations require that human lives and safety are prioritized. In addition, it is only through controlled, laboratory studies that the effectiveness of a vaccine can be adequately and most rapidly measured.
During the SARS outbreak, it took just 20 months to go from genetic sequence to the first phase of human trials. Because of animal research into the SARS coronavirus as well as other diseases which share the similar mechanisms of action for infection, over 160 candidate vaccines and treatments for COVID-19 are being tested for safety and efficacy—a mere 3 months after declaration of the pandemic.
Why are candidate vaccines tested in animals?
Generally, the safety and efficacy of all vaccines (just like all other medications) are tested in animals before making their way to clinical (human) trials. Because of the urgency of the current threat, however, safety and efficacy testing for some new candidates (e.g., Moderna’s mRNA-1273 vaccine) for COVID-19 has been fast-tracked and is being conducted in Phase 1 clinical trials—where typically the lowest number of human subjects are enrolled. That is not to say that safety and efficacy is not being evaluated in animals for those candidates, however. Instead safety and efficacy is being evaluated in animals in tandem with human trials, rather than prior to human trials.
The ethics of such decisions has been questioned in some editorials. For example, in a recent Nature editorial:
“Testing vaccines and medicines without taking the time to fully understand safety risks could bring unwarranted setbacks during the current pandemic, and into the future. The public’s willingness to back quarantines and other public-health measures to slow spread tends to correlate with how much people trust the government’s health advice. A rush into potentially risky vaccines and therapies will betray that trust and discourage work to develop better assessments. Despite the genuine need for urgency, the old saying holds: measure twice, cut once.”
Part of the reason why animal research safety data is not being provided for some vaccine and treatment candidates is that the traditional animal model used in initial tests, the laboratory mouse, does not get sick from the coronavirus. If mice are to be used, a special mouse is needed—one that contains human genes—a “humanized” mouse. Such a mouse exists, and was created during the SARS epidemic. This mouse contains the human ACE2 gene and was developed by researchers at the University of Iowa. Sperm from these mice were cryopreserved, and these sperm have now been sent to the Jackson Laboratories for recovery and mass production. The process from “unfreezing” to breeding, and waiting for the animals to grow before they can be used in experiments takes approximately 12 weeks (3 months). After that, experiments can be performed and those may take another few months.
Other animal species, such as mice, monkeys, cats, dogs, ferrets, chickens, and even horses are also being used in our fight against COVID-19 to address pertinent questions such as:
- Do animals develop immunity?
- If so, for how long?
- Are there species differences?
- What does that immune response look like?
- Do any vaccine candidates elicit unwanted effects?
Already, animal research is providing answers to these key questions and raising hopes for the development of both preventive measures (such as vaccines) as well as cures.
In our subsequent posts over the next few days, we will re-post some of our #Evergreen content which highlights the historical aspects that lead to the “anti-vaxxer” movement (part 1) and why critical consideration of the facts pertaining to that movement is warranted (parts 2 and 3). Finally, we highlight some of the longer term repercussions of not pushing back against such misinformation as it affects health and well-being at a global scale (part 4).
~Speaking of Research