Potential Single-dose COVID-19 Vaccine Trial Published in Nature

A possible vaccine to protect against the SARS-CoV-2 virus that causes COVID-19 has been tested and found effective and safe in several animal models by a team of scientists at the Rega Institute in Leuven, Belgium. A significant part of the research includes vaccine trials with genetically engineered golden Syrian hamsters developed by Professor Zhongde Wang and his lab at Utah State University.

The study, A single-dose live-attenuated YF17D-vectored SARS-CoV-2 vaccine candidate, was published online in the journal Nature on December 1. The announcement came as global cases of COVID-19 topped 63,478,000 and global deaths since the beginning of the pandemic were at 1,472,917 according to the Johns Hopkins University Coronavirus Resource Center.

Hamsters in the study are genetically engineered to allow scientists to investigate the roles of interferons in response to vaccination or infection. Interferons are proteins secreted by cells and are among the body’s first responses to a virus infection. Interferons do not prevent a virus from multiplying, but they trigger a response in nearby cells that prevents a virus from replicating in them. But in some human populations, such as people who have certain underlying conditions, interferons do not respond well to infection.

Using CRISPR/Cas9 gene-editing technology, Wang and colleagues at USU developed golden Syrian hamsters with specific genes (STAT2) “knocked out” (KO) so the animals’ immune responses to vaccination or infection more closely match human responses in populations of people whose STAT2 genes do not respond to viral infection efficiently. In this study, the KO hamsters provided the unique opportunity to test STAT2 gene-mediated responses in evaluating the effectiveness and safety of a new vaccine.

According to the current study, the candidate vaccine — tentatively named YF-S0 — has a “remarkable safety profile” and induced high levels of SARS-CoV-2 neutralizing antibodies and immunity protection in the KO hamsters, mice, and cynomolgus macaques. All vaccines must be tested in multiple non-human animal species before they can move into clinical trials in humans.

Scientists at the Rega Institute used a live yellow fever virus vaccine as the basis for a possible COVID-19 vaccine. They found that a single dose of the candidate YF-S0 vaccine protected against COVID-19 lung disease in most of the KO hamsters within 10 days of being vaccinated.

A yellow fever vaccine (YF17D) known for its outstanding ability to rapidly induce immunity after a single dose is the basis for the new candidate vaccine. The YF17D backbone is already in two licensed human vaccines used against Japanese encephalitis virus and dengue virus.

The study’s authors note that, while the YF17D vaccine has an outstanding safety profile, in extremely rare cases it may result in disease that causes organ dysfunction in some humans. The STAT2 KO hamsters, because of their super-susceptibility to viral infections, including SARS-CoV-2, allowed researchers to evaluate the vaccine’s safety at a level of sensitivity that other animal models cannot match. By using the super-sensitive hamster model, the authors showed that the new YF-S0 vaccine is effective and safer than the YF17D vaccine on which it is based.

The Wang lab pioneered the development of genetic engineering techniques in this species and developed the first genetic hamster models in the world. The hamster model is being used in more than a dozen labs and institutions in several countries, including the National Institutes of Health, the U.S. Army Medical Research Institute of Infectious Diseases, and Public Health Agency of Canada.

“We take animal welfare extremely seriously, and only the minimum numbers of animals required are used,” Wang said. “In addition to that, all procedures are approved by Institutional Animal Care and Use Committees. It is essential to use these animals in vaccine studies before trials can be done in human subjects.”

Because the hamsters are designed specifically to react disease challenges more like humans, fewer experiments are necessary to verify results, which expedites the process and can reduce the number of animals used in research. Many of the KO hamsters from Wang’s lab are important in COVID-19 and other studies in USU’s Institute for Antiviral Research. Hamsters in the study published in Nature are from a breeding colony established at the Rega Institute in an agreement with Wang’s lab.

“The scientists in my lab and I are very gratified that our research is contributing to combating this raging COVID-19 pandemic,” Wang said. “We also feel grateful for the excellent support from USU’s Laboratory Animal Research Center to help us to carry out the research.”

The paper is available online at nature.com/articles/s41586-020-3035-9.

The Digital Object Identifier number for this paper is 10.1038/s41586-020-3035-9.