Mice were immunized with a combination of self-amplifying (sa) RNA constructs
for the F1 and V antigens of Yersinia pestis at a dose level of 1  μg or 5  μg or with
the respective protein sub-units as a reference vaccine. The immunization
of outbred OF1 mice on day 0 and day 28 with the lowest dose used (1  μg) of
each of the saRNA constructs in lipid nanoparticles protected 5/7 mice against
subsequent sub-cutaneous challenge on day 56 with 180  cfu (2.8 MLD) of a 2021
clinical isolate of Y. pestis termed 10-21/S whilst 5/7 mice were protected against
1800cfu (28MLD) of the same bacteria on day 56. By comparison, only 1/8 or
1/7 negative control mice immunized with 10  μg of irrelevant haemagglutin RNA
in lipid nanoparticles (LNP) survived the challenge with 2.8 MLD or 28 MLD Y.
pestis 10-21/S, respectively. BALB/c mice were also immunized with the same
saRNA constructs and responded with the secretion of specific IgG to F1 and
V, neutralizing antibodies for the V antigen and developed a recall response to
both F1 and V. These data represent the first report of an RNA vaccine approach
using self-amplifying technology and encoding both of the essential virulence
antigens, providing efficacy against Y. pestis. This saRNA vaccine for plague has
the potential for further development, particularly since its amplifying nature can
induce immunity with less boosting. It is also amenable to rapid manufacture
with simpler downstream processing than protein sub-units, enabling rapid
deployment and surge manufacture during disease outbreaks.