The modified common cold viruses behind the high-profile COVID-19 vaccine candidates from CanSino Biologics of China and the Gamaleya Institute of Russia have been studied for decades, but are not yet widely used.
The following are some details of their development, how they work, and past and potential future uses:
WHEN WERE THESE VIRUSES FIRST ON MEDICAL INVESTIGATION?
The modified adenovirus type 5 (Ad5) viruses used in these vaccines were first created by Canadian researcher Dr. Frank Graham in a Dutch laboratory in the 1970s.
Graham planned to use them to study the mechanisms underlying cancer and distributed the human kidney cell line that produces them, called HEK293, to researchers around the world.
“The cells became tremendously widespread and popular” with researchers, said Graham, now retired in Italy.
WHAT VECTORS ARE USED IN VACCINES AND HOW DO THEY WORK?
Vectors are materials used as mechanisms to transport genetic information to human cells. Modified viruses that cannot replicate themselves and therefore will not cause infection can be used as vectors to transport genes from the target virus to human cells to induce an immune response against that virus.
Ad5 vectors were tested in early gene therapy, the goal of which is to install a missing gene or replace a mutated or damaged one. They were largely abandoned after an 18-year-old died in 1999 from an overreaction of the immune system after receiving a large dose during a gene therapy trial.
Some researchers believe that the strong immune response that caused problems with gene therapy makes these vectors suitable for vaccines, where much lower doses are used and a protective immune response is the goal.
HAVE AD5 VECTORS BEEN SUCCESSFUL IN THE PAST?
At McMaster University in Canada, Graham and colleagues developed a variety of Ad5 vectors, including a rabies vaccine used in wild raccoons in the province of Ontario.
He and other researchers began developing an Ad5-based vaccine against severe acute respiratory syndrome (SARS) in 2003 and published preclinical data. It was put aside when the pandemic ended.
In 2011, CanSino licensed an experimental Ad5-based tuberculosis vaccine from McMaster researchers.
The Chinese company’s focus then switched to an Ad5-based Ebola vaccine at the request of the Chinese military, according to Dr. Thomas Evans, Vaccitech’s current scientific director, who was involved in the tuberculosis project. The Ebola vaccine was approved for military use in 2017.
Russia’s Gamaleya Research Institute, which developed Russia’s coronavirus vaccine, also used the Ad5 platform to develop an Ebola vaccine, which they said has been administered to about 2,100 people.
WHAT ELSE IS IN DEVELOPMENT USING AD5 VECTORS?
In addition to the Ad5-based COVID-19 vaccines, an inhaled version of the experimental tuberculosis vaccine is still being developed at McMaster, Dr. Zhou Xing told Reuters. His team is also in the early stages of developing an inhaled COVID-19 vaccine, testing Ad5 and another vector based on a chimpanzee adenovirus.
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