Self-replicative RNA vaccines elicit protection against influenza A virus, respiratory syncytial virus, and a tickborne encephalitis virus
Abstract
In genetic vaccination, recipients are immunized with antigen-encoding nucleic acid, usually DNA. This study addressed the possibility of using the recombinant alpha virus RNA molecule, which replicates in the cytoplasm of transfected cells, as a novel approach for genetic vaccination. Mice were immunized with recombinant Semliki Forest virus RNA-encoding envelope proteins from one of 3 viruses: influenza A virus, a tickborne flavivirus (louping ill virus), or respiratory syncytial virus (RSV). Serologic analyses showed that antigen-specific antibody responses were elicited. IgG isotyping indicated that predominantly Th1 type immune responses were induced after immunization with RSV F protein-encoding RNA, which is relevant for protection against RSV infection. Challenge infection showed that RNA immunization had elicited significant levels of protection against the 3 model virus diseases.
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Viral vector-based technologies are generally regarded as the most efficient means to deliver nucleic acids into cells, but their utility can be restricted by preexisting or vaccine-induced antivector immunity that can decrease vaccine potency.
“Viral vector-based technologies are generally regarded as the most efficient means to deliver nucleic acids into cells, but their utility can be restricted by preexisting or vaccine-induced antivector immunity that can decrease vaccine potency (12).”
From Nonviral delivery of self-amplifying RNA vaccines (2012) · cites this paper as [12]
Injection of naked mRNA or self-amplifying RNA in vivo induces gene expression and generates immune responses, with self-amplifying RNA being more efficient for gene expression in situ.
“Injection of naked mRNA or self-amplifying RNA in vivo induces gene expression and generates immune responses (4, 11-13), with self-amplifying RNA being more efficient for gene expression in situ (13,14).”
From Nonviral delivery of self-amplifying RNA vaccines (2012) · cites this paper as [12]
All self-amplifying RNA vaccines provided protection from a nasal RSV challenge, reducing the lung viral load >1,000-fold compared with control animals.
“All self-amplifying RNA vaccines provided protection from a nasal RSV challenge, reducing the lung viral load >1,000-fold compared with control animals (Fig. 5C) and these data are in agreement with previous reports for naked RNA (12).”
From Nonviral delivery of self-amplifying RNA vaccines (2012) · cites this paper as [12]
The unformulated RNA vaccine elicited serum F-specific IgG and RSV neutralizing antibodies after two vaccinations.
“As described for other naked self-amplifying RNA vaccines (12), the unformulated RNA vaccine elicited serum F-specific IgG and RSV neutralizing antibodies after two vaccinations (Fig. 5 A and B).”
From Nonviral delivery of self-amplifying RNA vaccines (2012) · cites this paper as [12]
The shorter duration of expression in situ after RNA immunization compared with pDNA may be related to the induction of apoptosis of the transfected cell, which could occur during RNA amplification, leading to transient gene expression.
“The shorter duration of expression in situ after RNA immunization compared with pDNA may be related to the induction of apoptosis of the transfected cell, which could occur during RNA amplification, leading to transient gene expression (12,13).”
From Nonviral delivery of self-amplifying RNA vaccines (2012) · cites this paper as [12]
saRNA can lead to high antigen production at a low dose along with intracellular RNA replication of the antigen of interest.
“Along with the intracellular RNA replication of the antigen of interest, saRNA can lead to high antigen production at a low dose.52”
From COVID-19 mRNA vaccines: Platforms and current developments (2022) · cites this paper as [52]
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- Authors
- Fleeton, M. N., Chen, M., Berglund, P., Rhodes, G., Parker, S. E., Murphy, M., Atkins, G. J., & Liljeström, P.
- Affiliations
- Karolinska Institutet (SE)
- University of California, Davis (US)
- Vical (United States) (US)
- Trinity College Dublin (IE)
- Swedish Institute (SE)
- Venue
- The Journal of Infectious Diseases
- Publisher
- Oxford University Press (OUP)
- Published
- 2001-05
- Volume
- 183
- Issue
- 9
- Pages
- 1395-1398
- ISSN
- 0022-1899 (ISSN-L)
- 1537-6613
- OpenAlex
- W2101764878
- Cited by
- 157
- References
- 16
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 10 · 2023: 11 · 2022: 21 · 2021: 18 · 2020: 8 · 2019: 6 · 2018: 6 · 2017: 4 · 2016: 3 · 2015: 2 · 2014: 9 · 2013: 6 · 2012: 3
- FWCI
- 3.26
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Infectious Diseases (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Instituto de Salud Carlos III
- Topics
- Health Sciences › Medicine › Epidemiology › Influenza Virus Research Studies
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Health Sciences › Medicine › Epidemiology › Respiratory viral infections research
- Keywords
- genetic immunization, influenza A virus, respiratory syncytial virus, louping ill virus, RSV F protein, Th1 response, antibody response, protective immunity
- MeSH terms
- Animals, Encephalitis Viruses, Tick-Borne, Encephalitis, Tick-Borne, Female, Immunoglobulin G, Immunity, Cellular, Influenza Vaccines, Mice, Inbred BALB C, Orthomyxoviridae Infections, Influenza A virus, Respiratory Syncytial Viruses, RNA, Viral, Semliki forest virus, Transfection, Vaccines, Synthetic, Viral Vaccines, Respiratory Syncytial Virus Infections, Th1 Cells, Respiratory Syncytial Virus Vaccines, Mice
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