Scientists have long been using viruses to deliver gene therapies or vaccines. Now, researchers at the University of Iowa and the University of Georgia are suggesting a virus that causes kennel cough in dogs could be used to construct vaccines against the novel coronavirus behind COVID-19.
In a study published in the journal mBio, the researchers showed that their vaccine, which is based on the parainfluenza virus 5 (PIV5) that’s believed to cause the canine respiratory disease, protected all mice from the lethal Middle East respiratory syndrome (MERS) virus.
The team suggested the idea could also be employed to develop a vaccine for COVID-19, the disease caused by SARS-CoV-2, because both MERS and the emerging pathogen that caused the current pandemic are coronaviruses.
PIV5 infects many mammals, including humans, but it doesn't cause diseases other than kennel cough in dogs. “We know people have been exposed to PIV5, but it seems to be an innocuous virus in humans,” said University of Iowa scientist Paul McCray, M.D., who co-led the study, in a statement. Because it’s an RNA virus that doesn’t have a DNA phase in its life cycle, it also doesn't cause unintended genetic modifications in host cells. Therefore, it could serve as an excellent viral vector for vaccine development, the researchers said.
The team had previously designed PIV5-based vaccines against influenza, respiratory syncytial virus and rabies, showing strong efficacy in mice.
In their new study, the researchers used PIV5 to carry a gene that codes for the spike protein of MERS. Both MERS-CoV and SARS-CoV-2 attach to the host cell via the spike, or S protein, which then fuses its own viral membrane with that of the host cell to deliver the viral genome and touch off the infection.
In genetically engineered mice that could contract MERS, a single dose of the vaccine prompted the cells to make the S protein, which then triggered an immune response marked by the production of neutralizing antibodies and CD8 T cells, the team reported.
To test whether the immunity would translate to protection, the scientists exposed the mice to a lethal MERS infection. All the mice immunized with the vaccine survived, the team found. In contrast, those that got PIV5 without S protein died from the infection. A vaccine made from inactivated MERS virus only protected 25% of mice from death, and it increased levels of eosinophils, which are white blood cells that indicate infection or inflammation. “These results suggest that inactivated MERS-CoV may have caused a hypersensitivity-type response,” raising a safety concern, the researchers said.
As the current pandemic escalates around the world, many biopharma companies and research teams are rushing to develop COVID-19 vaccines. And the spike protein is the main focus of a lot of those candidates.
China’s CanSino Bio and the Academy of Military Medical Sciences’ Institute of Biotechnology recently started human testing of their recombinant vaccine, which uses adenovirus type 5 as the vector to express the SARS-CoV-2 spike protein. Moderna and collaborators at the National Institutes of Health have also started a clinical trial of an mRNA vaccine, dubbed mRNA-1273, which encodes for a prefusion stabilized form of the S protein. A University of Oxford team, with funding from the U.K. government, is testing a shot that uses a chimpanzee adenovirus vector to deliver the genetic sequence of the S protein.
McCray and colleagues are now working on a SARS-CoV-2 vaccine that uses PIV5 to express the S protein from the new coronavirus. "We don't know yet if people get lasting immunity from the SARS-CoV-2 infection, so it's important to think about ways to protect the population," he said.