Self-Amplifying RNA Vaccines Give Equivalent Protection against Influenza to mRNA Vaccines but at Much Lower Doses



Make your own vaccine
With pandemic infections we are always behind the curve,
particularly when it comes to developing vaccines. Vaccines work by inducing a
protective immune memory to an infectious agent so you have to know what the
infectious agent is and which part of the infectious agent the body is going to
recognise to make an effective vaccine. Having identified that, you then have
to make the vaccine, test the vaccine and ship it to the sites where it is
needed in order to give it to people before they are exposed to the infection.
This all takes time.

Manufacture = time
A particularly time consuming hurdle is vaccine manufacture.
This is because most vaccines that we use are protein based, which can be
difficult (and expensive) to manufacture. There are however alternatives. One
approach is to utilise our understanding of how proteins are encoded in our
cells. The source information for proteins comes from genes (encoded in DNA
molecules), this genetic material is copied into an intermediary messenger
molecule called ribonucleic acid (RNA). Remarkably, if you inject either DNA or
RNA into a muscle, that muscle starts making the protein encoded in the DNA.
Even more amazingly, your immune system can then recognise the protein that is
made in your muscle cells and develop a protective response, in the same way
that it would to an injected vaccine.
RNA vaccines
The injection of RNA in particular, seems to be very
effective at triggering an immune response. In our recently published
paper
, we looked at ways to improve how these RNA vaccines work. We compared
two different approaches, the first approach is to make synthetic RNA molecules
that look exactly like the messenger RNA (mRNA) your body makes when it is
making a protein. The second approach is to adapt a trick from a family of
viruses called the alpha viruses, which use the machinery of the cell to make
copies of themselves. We can insert vaccine genes into a safe version of the
alphavirus, which when injected makes multiple copies of the vaccine in the cells
it has been injected into. We call these vaccines self-amplifying as they are
able make more copies of themselves after they are injected.

We compared the two RNA approaches to see which one would
make the best influenza vaccine. Both the mRNA and the self-amplifying RNA
based vaccines protected against influenza virus infection, but strikingly the self-amplifying
vaccines gave the same protection when 60 times less RNA was used. This dose
sparing could potentially be really important in the face of an epidemic where
many people need to be vaccinated in a short time period. We also show that the
vaccine was able to protect after a single dose and it is possible to combine
multiple strains of influenza virus in the same vaccine and protect against all
of them.



We think RNA vaccines show great promise for the future and
this study gives us confidence to move forwards into human studies.