An alphavirus replicon particle chimera derived from Venezuelan equine encephalitis and sindbis viruses is a potent gene-based vaccine delivery vector

Perri, Silvia; Greer, Catherine E.; Thudium, Kent; Doe, Barbara; Legg, Harold; Liu, Hong; Romero, Raul E.; Tang, Zequn; Bin, Qian; Dubensky, Thomas W.; Vajdy, Michael; Otten, Gillis R.; Polo, John M.

doi:10.1128/jvi.77.19.10394-10403.2003

Cited by 172Immunotherapy and Immune ResponsesMosquito-borne diseases and controlHIV Research and Treatment

An alphavirus replicon particle chimera derived from Venezuelan equine encephalitis and sindbis viruses is a potent gene-based vaccine delivery vector

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Perri, Silvia, Greer, Catherine E., Thudium, Kent, Doe, Barbara, Legg, Harold, Liu, Hong, Romero, Raul E., Tang, Zequn +5 more·2003·Journal of Virology

DOI 10.1128/jvi.77.19.10394-10403.2003PMC PMC228391

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Abstract

Alphavirus replicon particle-based vaccine vectors derived from Sindbis virus (SIN), Semliki Forest virus, and Venezuelan equine encephalitis virus (VEE) have been shown to induce robust antigen-specific cellular, humoral, and mucosal immune responses in many animal models of infectious disease and cancer. However, since little is known about the relative potencies among these different vectors, we compared the immunogenicity of replicon particle vectors derived from two very different parental alphaviruses, VEE and SIN, expressing a human immunodeficiency virus type 1 p55(Gag) antigen. Moreover, to explore the potential benefits of combining elements from different alphaviruses, we generated replicon particle chimeras of SIN and VEE. Two distinct strategies were used to produce particles with VEE-p55(gag) replicon RNA packaged within SIN envelope glycoproteins and SIN-p55(gag) replicon RNA within VEE envelope glycoproteins. Each replicon particle configuration induced Gag-specific CD8(+) T-cell responses in murine models when administered alone or after priming with DNA. However, Gag-specific responses varied dramatically, with the strongest responses to this particular antigen correlating with the VEE replicon RNA, irrespective of the source of envelope glycoproteins. Comparing the replicons with respect to heterologous gene expression levels and sensitivity to alpha/beta interferon in cultured cells indicated that each might contribute to potency differences. This work shows that combining desirable elements from VEE and SIN into a replicon particle chimera may be a valuable approach toward the goal of developing vaccine vectors with optimal in vivo potency, ease of production, and safety.

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VRPs are potent vaccines in mice, nonhuman primates, and humans.
“VRPs are potent vaccines in mice (10,11), nonhuman primates (11,22), and humans (25).”
From Nonviral delivery of self-amplifying RNA vaccines (2012) · cites this paper as [10]
Insertion of an RNA-dependent RNA polymerase (RdRp) sequence next to the antigen-encoding sequence leads to amplification of the antigen of interest in the cytoplasm.
“Subsequent viral biology research led to the insertion of an RNA-dependent RNA polymerase (RdRp) sequence next to the antigen-encoding sequence, leading to the amplification of the antigen of interest in the cytoplasm.51”
From COVID-19 mRNA vaccines: Platforms and current developments (2022) · cites this paper as [51]

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Authors: Perri, S., Greer, C. E., Thudium, K., Doe, B., Legg, H., Liu, H., Romero, R. E., Tang, Z., Bin, Q., Dubensky, T. W., Vajdy, M., Otten, G. R., & Polo, J. M.
Affiliations: Vaccine Research, Chiron Corporation, Emeryville, California 94608
Corresponding author: Perri, Silvia
ORCID: Perri, Silvia
Thudium, Kent
Liu, Hong
Dubensky, Thomas W.
Otten, Gillis R.
Venue: Journal of Virology
Publisher: American Society for Microbiology
Published: 2003-10
Volume: 77
Issue: 19
Pages: 10394-10403
ISSN: 0022-538X (ISSN-L)
1098-5514
DOI: 10.1128/jvi.77.19.10394-10403.2003
PMC: PMC228391
OpenAlex: W2153049488
Cited by: 172
References: 62
Citations by year: 2026: 3 · 2025: 4 · 2024: 9 · 2023: 10 · 2022: 12 · 2021: 11 · 2020: 13 · 2019: 7 · 2018: 6 · 2017: 2 · 2016: 6 · 2015: 3 · 2014: 8 · 2013: 9 · 2012: 6
FWCI: 2.27
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
Locations: Journal of Virology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (n01ai005396-002)
National Institute of Allergy and Infectious Diseases (N0-1-AI-05396, N01 AI005396)
Topics: Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Mosquito-borne diseases and control
Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
Keywords: Venezuelan equine encephalitis virus, Sindbis virus, Semliki Forest virus, envelope glycoprotein, CD8+ T cell responses, interferon sensitivity, immunogenicity, DNA priming, heterologous expression
MeSH terms: Amino Acid Sequence, Animals, Chimera, Encephalitis Virus, Venezuelan Equine, Genetic Vectors, Cricetinae, Interferons, Mice, Inbred BALB C, Molecular Sequence Data, Protein Precursors, Replicon, RNA, Viral, Sindbis Virus, Vaccines, Synthetic, Gene Products, gag, AIDS Vaccines, CD8-Positive T-Lymphocytes, Virus Assembly, Mice

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An alphavirus replicon particle chimera derived from Venezuelan equine encephalitis and sindbis viruses is a potent gene-based vaccine delivery vector

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