Island firm speeds coronavirus vaccines toward tests

Driving the spike: The way COVID-19 attaches to host cells -- and Applied DNA's unique DNA-production abilities -- could lead to a vaccine against the dreaded coronavirus.
By GREGORY ZELLER //

Just weeks after announcing an expanded international collaboration targeting the menacing novel coronavirus, Applied DNA Sciences is preparing to mass-produce four potential vaccines.

Leveraging the Stony Brook-based biotech’s unique DNA-manufacturing abilities, Rome, Italy-based Takis Biotech will test potential vaccines against the coronavirus (now going by COVID-19) in laboratory mice, on a large scale.

Applied DNA expects delivery of four DNA-based “preclinical vaccine candidates” from Takis this month, and “within weeks” will use its proprietary, polymerase chain reaction-based DNA-sequencing technology to reproduce each for immediate animal testing.

“We expect to immediately scale up PCR-based production of each vaccine candidate and ship them back to Takis, who will determine each vaccine’s relative abilities to provoke an immune response in vaccinated mice,” Applied DNA President and CEO James Hayward said Monday.

James Hayward: Quick turnaround.

Both Applied DNA and Takis were quick to note that no commercial partner has been named, nor any guarantee that potential vaccines will ultimately receive regulatory approvals. But Applied DNA’s unique “linear DNA” technology – officially wielded by 2018 spinoff LineaRX – and Takis’ ability to manipulate protein structures make for a powerful antiviral combo.

The collaboration has designed the four preclinical vaccines based on COVID-19’s “spike” protein structure, which essentially binds the virus to host cells. One of the vaccine candidates encompasses the entire spike gene; the other three are variants based on “epitope mapping,” which targets specific points where antibodies and antigens bind.

The science thickens quickly from there. In fact, feel free to skip the next paragraph…

The epitope mapping identifies the likeliest antigenic portions of the spike protein and helps assemble corresponding parts of the multifunctional S gene into a new “synthetic linear DNA” gene – essentially, the vaccine. Codon optimization (improving the codon composition of a recombinant gene) ensures the new linear DNA vaccine genes are “efficiently expressed as proteins,” according to Applied DNA, “once the genes have been delivered to a small percentage of the nuclei of the patient’s muscle cells.”

…and rejoin here secure in the knowledge that Applied DNA and Takis know all about S genes and codon optimization. The Stony Brook biotech also has fresh patents pending for “genetic ensembles” that could make the candidate vaccines work even better, “if the results obtained in animal studies warrant this consideration.”

Count on it, according to Hayward, who noted rapid development and large-scale production aren’t the only advantages to this international association.

“Our patented and proprietary platform for the production of linear DNA … has the potential to yield an effective vaccine with fewer risks than other currently utilized DNA-production platforms,” Hayward said, noting the same technology would also be standing by later, when the novel coronavirus invariably novelizes again.

“As is typical for RNA viruses, coronaviruses mutate at rapid rates that require constant surveillance,” he added. “One of the many benefits of PCR-produced linear DNA is the rapidity at which a putative vaccine can be revised to accommodate mutational drift.”

The promising developments come amid a global race to stop COVID-19. Right now, the novel coronavirus is easily outpacing human science – 90,000 global infections (and spreading fast) leading to 3,000-plus deaths, including two in the United States.

With new cases reported on every continent (except Antarctica), this weekend brought the first confirmed New York State case – a New York City healthcare worker said to have contracted the virus overseas – and pushed the U.S. count rapidly toward 90, with that number expected to rise fast.

Luigi Aurisicchio: Velocemente!

The New York case prompted an immediate response from Gov. Andrew Cuomo, who noted the healthcare worker is suffering “respiratory symptoms, but is not in serious condition” and is “currently isolated in her home.” Across the nation, lawmakers, healthcare systems, schools and other stakeholders have issued similar statements – tracking outbreaks, urging common-sense precautions and noting the response community’s readiness.

Cuomo, who last week asked the State Legislature to approve a $40 million emergency-management fund to deal with the evolving coronavirus situation, stressed that the arrival of COVID-19 in New York was inevitable, and no cause for alarm.

“This was expected,” the governor said. “As I said from the beginning, it was a matter of when, not if, there would be a positive case of novel coronavirus in New York.

“There is no reason for undue anxiety,” Cuomo added. “The general risk remains low in New York.”

Despite COVID-19’s rapid spread, and some undeniably heavy-handed media coverage, the general risk remains low everywhere – at least, the risk of dying from the novel coronavirus.

According to global stat-tracker Worldometer, about 82 percent of worldwide novel coronavirus patients are in “mild condition,” while even media outlets have begun noting that COVID-19’s reputation as a stone-cold killer has been somewhat overplayed.

Of course, the contagious virus is still a massive public health threat – not to mention global economic threat – and to that end, Applied DNA and Takis can’t work fast enough on their vaccine candidates, according to Takis Biotech CEO Luigi Aurisicchio.

“For the induction of antibodies that can neutralize COVID-19, it is essential to use reliable, effective technologies that can be quickly adapted in the face of shifting pathogens,” Aurisicchio said in a statement. “We believe that is the advantage that Applied DNA’s platform affords us over traditional vaccine development and other modern DNA-based vaccines.

“This global emergency requires a swift response.”