A COVID-19 vaccine being developed by Chinese company CanSino Biologics delivered mixed results in a Phase 1 trial.
The trial found that the vaccine, which contains a weakened adenovirus 5 with SARS-CoV-2 genetic material fused onto it, generated an immune response in subjects. However, volunteers with preexisting immunity to adenovirus 5 (Ad5) saw a dampened immune response to SARS-CoV-2.
Many research groups have stopped using Ad5 for vaccines because of concerns that immune systems will focus on the Ad5 parts of vaccines instead of the extra, fused genetic material researchers want the immune system to focus on.
“This is definitely one of the concerns about using vectored vaccines for which people might already have preexisting immunity,” said Harvard’s Michael Mina.
“If you already have seen a virus or have some preexisting immunity to it… you run the risk of having your immune response get skewed and picking up primarily the thing you’re already immune to or that you’ve already seen and not focusing so much on the new aspect, which in this case would be the coronavirus proteins that were placed onto the adenovirus vector,” he said.
The immune systems of volunteers in the study with no preexisting immunity to Ad5 generated more SARS-CoV-2 antibodies compared to volunteers with preexisting Ad5 immunity. The immune systems of volunteers with preexisting Ad5 immunity generated more Ad5 antibodies compared to volunteers with no preexisting Ad5 immunity.
Preexisting Ad5 immunity was more common in older volunteers, raising concerns about how effective the vaccine can be in older adults who really need the vaccine since their age makes them more susceptible to more serious COVID-19 symptoms on average.
“This probably wouldn’t be a vaccine that you would want to give to the people over 65, because they may have higher levels [of preexisting immunity],” said Vanderbilt’s Kathryn Edwards.
Laval University’s Gary Kobinger said these results were expected and he doesn’t expect the vaccine to succeed.
“This was the assumption and they are just demonstrating that the assumption was correct,” he said.
Kobinger said CanSino has said it could deal with the problem of preexisting Ad5 immunity by using higher doses. However, the largest dose in the trial saw at least 75% of volunteers report at least one side effect. 17% of volunteers receiving the highest dose in the study reported serious side effects.
Edwards said it is not known how much of an immune response is necessary to prevent COVID-19 infection and that the dampened immune responses seen in patients with preexisting Ad5 immunity may be sufficient to prevent infection.