As has been
clearly shown during the COVID-19 pandemic, RNA vaccines are an incredibly
powerful tool. We have seen how potent they are against a rapidly emerging
infection, with the speed at which they can be produced a major benefit. From
the first genome sequence published to the first experimental vaccine dose
designed, manufactured and administered was seventy-one days, less time than it
takes to make cheese. However, more work is needed to deliver on the promising
start that RNA vaccines have had.
One of the
challenges has been with the side effects of the vaccine, sometimes called
reactogenicity. This is in part caused by the body’s reaction to the vaccine
itself: RNA is a trigger for immune reactions, it is how the body sees viral
infections. Tweaking the amount of RNA in the vaccine, whilst maintaining its
ability to induce a protective antibody response is one way in which we can
improve RNA vaccines.
We have been
interested in a slightly different approach, called self-amplifying vaccines.
We showed (pre-pandemic) that these saRNA vaccines can lead to protection for a
much lower dose. These vaccines are based on RNA, but
able to make more copies of themselves in the injected muscle, giving you more
bang for your buck. Professor Robin Shattock (also at Imperial College London)
performed the first in human clinical study using saRNA vaccines during the
pandemic. This trial had a mixed result, with not all of the volunteers
producing antibodies after vaccination. In parallel with this first in human
study, we looked at how the vaccine might work in other model organisms, as a
way to understand how these vaccines work.
In our recent
study Polymer
Formulated Self-Amplifying RNA Vaccine is Partially Protective against
Influenza Virus Infection in Ferrets, we tested the immune response to
saRNA vaccines in ferrets. This might sound like an odd choice, but ferrets
have a number of similarities to humans in they way they respond to infections,
especially influenza. We set out to test whether saRNA vaccines could protect
ferrets against flu. As with the human study, we had mixed results. The ferrets
that responded to the vaccine by making antibody were well protected against
infection, however, not all of the ferrets made antibodies. Understanding why
this is the case is important in the future development of this extremely
promising vaccine platform.
