Cited by 63Mosquito-borne diseases and controlRNA Interference and Gene DeliverySARS-CoV-2 and COVID-19 Research

Self-Amplifying RNA Vaccines for Venezuelan Equine Encephalitis Virus Induce Robust Protective Immunogenicity in Mice

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Samsa, Marcelo M., Dupuy, Lesley C., Beard, Clayton W., Six, Carolyn M., Schmaljohn, Connie S., Mason, Peter W., Geall, Andrew J., Ulmer, Jeffrey B. +1 more·2019·Molecular Therapy

Abstract

Venezuelan equine encephalitis virus (VEEV) is a known biological defense threat. A live-attenuated investigational vaccine, TC-83, is available, but it has a high non-response rate and can also cause severe reactogenicity. We generated two novel VEE vaccine candidates using self-amplifying mRNA (SAM). LAV-CNE is a live-attenuated VEE SAM vaccine formulated with synthetic cationic nanoemulsion (CNE) and carrying the RNA genome of TC-83. IAV-CNE is an irreversibly-attenuated VEE SAM vaccine formulated with CNE, delivering a TC-83 genome lacking the capsid gene. LAV-CNE launches a TC-83 infection cycle in vaccinated subjects but eliminates the need for live-attenuated vaccine production and potentially reduces manufacturing time and complexity. IAV-CNE produces a single cycle of RNA amplification and antigen expression without generating infectious viruses in subjects, thereby creating a potentially safer alternative to live-attenuated vaccine. Here, we demonstrated that mice vaccinated with LAV-CNE elicited immune responses similar to those of TC-83, providing 100% protection against aerosol VEEV challenge. IAV-CNE was also immunogenic, resulting in significant protection against VEEV challenge. These studies demonstrate the proof of concept for using the SAM platform to streamline the development of effective attenuated vaccines against VEEV and closely related alphavirus pathogens such as western and eastern equine encephalitis and Chikungunya viruses.

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  • Lipid nanoparticle-mRNA vaccines have been tested against other viruses in animal models, including human immunodeficiency virus, Powassan virus, Venezuelan equine encephalitis virus, dengue virus and Ebola virus.

    “Furthermore, lipid nanoparticle–mRNA vaccines have been tested against other viruses in animal models, including human immunodeficiency virus28,144,181,190, Powassan virus195, Venezuelan equine encephalitis virus196, dengue virus73 and Ebola virus197.”

    From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [196]

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  1. [23]23. [Geall, A.J., Settembre, E.C., and Ulmer, J.B. (2014). Using self-amplifying mRNA vaccines to facilitate a rapid response to pandemic in fl uenza. European Pharmaceutical Review 19 , 20 -23.](http://refhub.elsevier.com/S1525-0016(19)30001-2/sref23)
  2. [50]50. [Schmaljohn, A.L., Johnson, E.D., Dalrymple, J.M., and Cole, G.A. (1982). Nonneutralizing monoclonal antibodies can prevent lethal alphavirus encephalitis. Nature 297 , 70 -72.](http://refhub.elsevier.com/S1525-0016(19)30001-2/sref50)
  3. [59]59. [Hodgson, L.A., Ludwig, G.V., and Smith, J.F. (1999). Expression, processing, and immunogenicity of the structural proteins of Venezuelan equine encephalitis virus from recombinant baculovirus vectors. Vaccine 17 , 1151 -1160.](http://refhub.elsevier.com/S1525-0016(19)30001-2/sref59)

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Authors
Samsa, M. M., Dupuy, L. C., Beard, C. W., Six, C. M., Schmaljohn, C. S., Mason, P. W., Geall, A. J., Ulmer, J. B., & Yu, D.
Affiliations
  • GlaxoSmithKline (United States) (US)
  • United States Army Medical Research Institute of Infectious Diseases (US)
Corresponding author
  • Samsa, Marcelo M.
  • Yu, Dong
Venue
Molecular Therapy
Publisher
Elsevier BV
Published
2019-04
Volume
27
Issue
4
Pages
850-865
ISSN
1525-0016 (ISSN-L)
OpenAlex
W2910686626
Cited by
63
References
60
Citations by year
2026: 5 · 2025: 6 · 2024: 9 · 2023: 12 · 2022: 8 · 2021: 14 · 2020: 8 · 2019: 1
FWCI
7.13
Type
journal article
Language
en
Open access
Locations
  • Molecular Therapy (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Joint Science and Technology Office for Chemical and Biological Defense (W81XWH-11-0294 A7)
  • USAMRIID
  • Novartis Vaccines/GlaxoSmithKline Biologicals SA
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Mosquito-borne diseases and control
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
  • Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
Keywords
Venezuelan equine encephalitis virus, self-amplifying mRNA, live attenuated vaccine, cationic nanoemulsions, chikungunya virus, western equine encephalitis virus, eastern equine encephalitis virus, vaccine immunogenicity
MeSH terms
Immunogenicity, Vaccine, A549 Cells, Animals, Antibodies, Viral, Disease Models, Animal, Emulsions, Encephalitis Virus, Venezuelan Equine, Encephalomyelitis, Venezuelan Equine, Female, Gene Amplification, Humans, Mice, Inbred BALB C, RNA, Messenger, Transfection, Vaccines, Attenuated, Viral Vaccines, Virus Replication, Mice, Antibodies, Neutralizing

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