April 3rd 2020
We are facing a major health threat in the COVID-19 disease, which is caused by the SARS-CoV-2 virus. The World Health Organization (WHO) has officially declared it a pandemic, with over 1 million cases (972,640 confirmed cases and 50,325 deaths) and with global fear and uncertainty increasing.
As we wrote in January, animal research will and has played an integral role in the development of a vaccine for this disease. Yesterday, researchers at the University of Pittsburgh reported that they have created a potential vaccine candidate against COVID-19.
This research published in eBioMedicine is the first peer-reviewed article to describe a candidate vaccine for COVID-19. Importantly, this breakthrough work depended on mice for its success. The researchers were able to act quickly because they had already laid the groundwork during earlier coronavirus epidemics, which also involved animal research.
Compared to the experimental mRNA vaccine candidate that recently entered clinical trials without proof of efficacy and safety in animals, the Pittsburgh CoronaVirus Vaccine described in this paper follows a more established approach, using lab-made pieces of viral protein to build immunity. It’s the same way the current flu shots work.
The researchers also used a novel approach to deliver the drug, called a microneedle array, to increase potency. This array is a fingertip-sized patch of 400 tiny needles that delivers the spike protein pieces into the skin, where the immune reaction is strongest. The patch goes on like a Band-Aid and then the needles—which are made entirely of sugar and the protein pieces—simply dissolve into the skin.
While the two strains of mice used in this study do not have the human ACE2 receptor to get sick from the SARS-CoV-2 virus (see below), the vaccine generated a surge of antibodies against SARS-CoV-2 within two weeks of the microneedle prick—sufficient to neutralize the virus for at least a year. This distinction may be important because the authors were not able to assess potential safety and efficacy issues in an established disease model.
The mice that would be needed for assessment of safety and efficacy and which develop COVID-19 are quite unique—they contain human genes—a “humanized” mouse. Such a mouse exists, and was created during the Severe Acute Respiratory Syndrome (SARS) epidemic and contains human ACE2 gene (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 develop before they can be used takes approximately 12 weeks (3 months). Then other experiments can be performed which may take another few months.
Other animal species, such as, baboons, rhesus macaques and other primate species are also being used in our fight against the coronavirus, COVID-19—but again, these experiments take time. These experiments will address pertinent questions such as: Do animals develop immunity? If so, for how long? What does that immune response look like? Do any vaccine candidates elicit unwanted effects?
The authors are now in the process of applying for an investigational new drug (IND) approval from the Food and Drug Administration in anticipation of starting a phase I human clinical trial in the next few months.
Senior co-author, Professor Louis Fallo stated:
“Testing in patients would typically require at least a year and probably longer. This particular situation is different from anything we’ve ever seen, so we don’t know how long the clinical development process will take. Recently announced revisions to the normal processes suggest we may be able to advance this faster.”
~Speaking of Research