Tonight, AstraZeneca announced that its COVID-19 vaccine study was put on hold due to a suspected reverse reaction in a trial participant in the United Kingdom. This event has triggered me to write more specifically about COVID-19 vaccines. I have purposely withheld my personal commentary on the relative benefits of the different COVID-19 vaccines, although I have to admit I have strong opinions related to the different formulations.
I would like to focus tonight’s blog on two parts of this particular vaccine’s story. The first is the unique formulation of the AstraZeneca/Oxford vaccine. The second is the implication of what it means to be put on clinical hold.
The AstraZeneca approach is unique among all of the different methods of creating a COVID-19 vaccine. Oxford University, AstraZeneca’s partner, decided to use a live adenovirus as the basis for their vaccine. In this manner AstraZeneca’s/Oxford’s vaccine is similar to the CanSino and Russian vaccines that both use adenovirus for their vaccines. These vaccines genetically modify the adenovirus to express a protein for COVID-19 and induce an immune response that could inactivate the SARS-CoV-2 virus and prevent this disease.
Oxford is different, however, in that they use a chimpanzee adenovirus instead of a human adenovirus as the basis for their vaccine.
Why would they use a chimpanzee adenovirus as the basis of their vaccine? It turns out that several years ago Oxford attempted to develop vaccines based on human adenoviruses. These vaccines failed, in part, because humans have strong immunity to their own adenoviruses because of exposure during their lifetimes. This immunity destroyed the vaccine before it could induce an immune response to the new proteins from the vaccine’s infection target.
Given Oxford’s difficulty in trying to develop human vaccines because of this immunity to the human adenovirus they tried a new approach. In order to escape human adenovirus immunity, the Oxford group decided to use a chimpanzee adenovirus to which humans had not been previously exposed. Their approach did demonstrate that humans did not have preexisting immunity to the chimpanzee virus. Despite this, this vaccine approach has not produced a licensed vaccine for human infections including Ebola, despite adding a smallpox vaccine booster. There are also doubts whether it even protected monkeys from COVID-19.
Maybe I just remember that HIV originally came from a monkey virus that got into the human population. Also, maybe it seems less than brilliant to treat a bat-derived coronavirus that has killed millions of humans with a chimp virus. Or I have just seen too many movies where the world came to an end because of a bizarre reaction to a novel virus (see the “I Am Legend” reboot with Will Smith). In any case, I feel very uneasy about injecting a LIVE virus from another species into millions of humans.
Aside from those issues, the likelihood of having an adverse reaction to a novel, live virus previously not present in humans would seem to be greater as compared to a killed virus, RNA or recombinant protein (like most of the other vaccine candidates). So, I am not a fan of the AstraZeneca/Oxford approach.
Compared to my personal concerns, the clinical hold announcement tonight is a relatively minor issue. The company itself initiated halting the clinical trial when it received the report of an adverse reaction. This was an entirely appropriate response and clearly showed that the company was monitoring the clinical trial in an exemplary manner. They will investigate the reaction seen in this individual and determine the cause and severity.
It is likely that if the reaction does not appear to be severe, cause long term damage to the individual, or is found to not be the result of the vaccine the clinical trial will resume. That would be appropriate to test this vaccine and compare it to other approaches.
If the trial does resume, however, don’t expect to see me show up as a volunteer. (Personal preference, not scientific fact).