Emily
Editor, Senior Moderator
https://cen.acs.org/pharmaceuticals/...OVID-19/98/i19
Adenoviral vectors are the new COVID-19 vaccine front-runners. Can they overcome their checkered past?
CanSino Biologics, Johnson & Johnson, and the University of Oxford are all using genetically engineered common cold viruses to make COVID-19 vaccines. The technology is more than 30 years in the making, but it’s yet to yield an effective vaccine for humans
by Ryan Cross
May 12, 2020 | APPEARED IN VOLUME 98, ISSUE 19
...
From failed gene therapy to vaccine
Adenovirus vaccines might be grabbing the limelight amid the coronavirus pandemic, but they have a checkered past.
....
The large dose of 38 trillion viruses the patient was given sparked massive body-wide inflammation and sent his immune system into overdrive. After that, scientists mostly stopped using adenoviral vectors for gene therapy, in which the dose needs to be high to reach many cells of the body.
But vaccine developers viewed adenovirus-induced inflammation as an asset.
“There is an expression out there that a failed gene therapy makes a good vaccine,” says Luk Vandenberghe, a viral vector expert at Harvard Medical School.
One attractive feature is that adenoviruses’ inflammatory effects mean developers don’t have to use adjuvants, molecules added to conventional vaccines to direct the immune system’s attention to the viral protein. The adenoviruses themselves drive the inflammation, which is kept under control by giving the vaccines at low doses.
...
Traditional vaccines, made from weakened viruses or viral proteins, stimulate B cells to make antibodies against the virus. Those antibodies latch onto invading viruses and prevent them from entering our cells.
The problem is that once the virus infiltrates our cells, the antibodies from a traditional vaccine are useless. It’s at that stage that T cells need to swoop in. Adenovirus vectors “are the best of all vaccines at inducing a T-cell response,” Wistar’s Ertl says.
That’s why some vaccine developers turned to adenoviral vectors in the early 2000s to tackle diseases, such as AIDS, malaria, and tuberculosis, caused by pathogens that hide out in cells. The largest, and most infamous, effort was led by Merck & Co., which had developed an Ad5-based vaccine for HIV. Two large clinical trials were halted early in 2007 when it became clear that the vaccine was not working—and, alarmingly, may have even increased the risk of HIV infections in a subset of people with preexisting immunity to Ad5.
“That put a big kibosh on adenoviruses for the next 5 years,” Vaccitech’s Evans says...
Adenoviral vectors are the new COVID-19 vaccine front-runners. Can they overcome their checkered past?
CanSino Biologics, Johnson & Johnson, and the University of Oxford are all using genetically engineered common cold viruses to make COVID-19 vaccines. The technology is more than 30 years in the making, but it’s yet to yield an effective vaccine for humans
by Ryan Cross
May 12, 2020 | APPEARED IN VOLUME 98, ISSUE 19
...
From failed gene therapy to vaccine
Adenovirus vaccines might be grabbing the limelight amid the coronavirus pandemic, but they have a checkered past.
....
The large dose of 38 trillion viruses the patient was given sparked massive body-wide inflammation and sent his immune system into overdrive. After that, scientists mostly stopped using adenoviral vectors for gene therapy, in which the dose needs to be high to reach many cells of the body.
But vaccine developers viewed adenovirus-induced inflammation as an asset.
“There is an expression out there that a failed gene therapy makes a good vaccine,” says Luk Vandenberghe, a viral vector expert at Harvard Medical School.
One attractive feature is that adenoviruses’ inflammatory effects mean developers don’t have to use adjuvants, molecules added to conventional vaccines to direct the immune system’s attention to the viral protein. The adenoviruses themselves drive the inflammation, which is kept under control by giving the vaccines at low doses.
...
Traditional vaccines, made from weakened viruses or viral proteins, stimulate B cells to make antibodies against the virus. Those antibodies latch onto invading viruses and prevent them from entering our cells.
The problem is that once the virus infiltrates our cells, the antibodies from a traditional vaccine are useless. It’s at that stage that T cells need to swoop in. Adenovirus vectors “are the best of all vaccines at inducing a T-cell response,” Wistar’s Ertl says.
That’s why some vaccine developers turned to adenoviral vectors in the early 2000s to tackle diseases, such as AIDS, malaria, and tuberculosis, caused by pathogens that hide out in cells. The largest, and most infamous, effort was led by Merck & Co., which had developed an Ad5-based vaccine for HIV. Two large clinical trials were halted early in 2007 when it became clear that the vaccine was not working—and, alarmingly, may have even increased the risk of HIV infections in a subset of people with preexisting immunity to Ad5.
“That put a big kibosh on adenoviruses for the next 5 years,” Vaccitech’s Evans says...
