Nonviral delivery of self-amplifying RNA vaccines.
Despite more than two decades of research and development on nucleic acid vaccines, there is still no commercial product for human use. Taking advantage of the recent innovations in systemic delivery of short interfering RNA (siRNA) using lipid nanoparticles (LNPs), we developed a self-amplifying RNA vaccine. Here we show that nonviral delivery of a 9-kb self-amplifying RNA encapsulated within an LNP substantially increased immunogenicity compared with delivery of unformulated RNA. This unique vaccine technology was found to elicit broad, potent, and protective immune responses, that were comparable to a viral delivery technology, but without the inherent limitations of viral vectors. Given the many positive attributes of nucleic acid vaccines, our results suggest that a comprehensive evaluation of nonviral technologies to deliver self-amplifying RNA vaccines is warranted.
Novartis Vaccines and Diagnostics, Cambridge, MA 02139, USA. andrew.geall@novartis.com
Andrew J
AJ
Geall
Ayush
A
Verma
Gillis R
GR
Otten
Christine A
CA
Shaw
Armin
A
Hekele
Kaustuv
K
Banerjee
Yen
Y
Cu
Clayton W
CW
Beard
Luis A
LA
Brito
Thomas
T
Krucker
Derek T
DT
O'Hagan
Manmohan
M
Singh
Peter W
PW
Mason
Nicholas M
NM
Valiante
Philip R
PR
Dormitzer
Susan W
SW
Barnett
Rino
R
Rappuoli
Jeffrey B
JB
Ulmer
Christian W
CW
Mandl
D000524:Alphavirus / Q000235:genetics; D000704:Analysis of Variance; D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods*; D004587:Electrophoresis, Agar Gel; D004926:Escherichia coli; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D008055:Lipids / Q000737:chemistry; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D034741:RNA, Small Interfering / Q000737:chemistry; D051381:Rats; D018709:Statistics, Nonparametric; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000235:genetics*
D008055:Lipids; D034741:RNA, Small Interfering; D019444:Vaccines, DNA