Nonviral delivery of self-amplifying RNA vaccines

被引：530

作者：

Geall, Andrew J. ^{[1
]}

Verma, Ayush ^{[1
]}

Otten, Gillis R. ^{[1
]}

Shaw, Christine A. ^{[1
]}

Hekele, Armin ^{[1
]}

Banerjee, Kaustuv ^{[1
]}

Cu, Yen ^{[1
]}

Beard, Clayton W. ^{[1
]}

Brito, Luis A. ^{[1
]}

Krucker, Thomas ^{[2
]}

O'Hagan, Derek T. ^{[1
]}

Singh, Manmohan ^{[1
]}

Mason, Peter W. ^{[1
]}

Valiante, Nicholas M. ^{[1
]}

Dormitzer, Philip R. ^{[1
]}

Barnett, Susan W. ^{[1
]}

Rappuoli, Rino ^{[1
]}

Ulmer, Jeffrey B. ^{[1
]}

Mandl, Christian W. ^{[1
]}

机构：

[1] Novartis Vaccines & Diagnost, Cambridge, MA 02139 USA

[2] Novartis Inst BioMed Res, Cambridge, MA 02139 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2012年 / 109卷 / 36期

关键词：

vaccine platform; SAM vaccine; respiratory syncytial virus; HIV; RESPIRATORY SYNCYTIAL VIRUS; MESSENGER-RNA; DNA VACCINES; ALPHAVIRUS VECTORS; VACCINATION TRIAL; DIRECT-INJECTION; SIRNA DELIVERY; GENE-TRANSFER; IN-VIVO; IMMUNITY;

D O I：

10.1073/pnas.1209367109

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

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.

引用

页码：14604 / 14609

页数：6

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