Generation of cytotoxic and humoral immune responses by nonreplicative recombinant Semliki Forest virus.
Open accessAbstract
The Semliki Forest virus (SFV) expression system can be used to package recombinant RNA into infectious suicide particles. Such RNA encodes only the SFV replicase and the heterologous protein but no structural proteins of SFV, and it is thus deficient in productive replication. We demonstrate here that infection of C57BL/6 (H-2b) and BALB/c (H-2d) mice with recombinant SFV expressing the nucleoprotein (NP) of influenza virus (SFV-NP) resulted in efficient priming of influenza virus-specific CD8+ cytotoxic T-cell (CTL) responses. The generated CTLs lysed both homologous (A/PR/8/34) and heterologous (A/HK/68) influenza virus-infected, or peptide-coated, target cells to a similar degree as CTLs induced by wild-type influenza virus in a major histocompatibility complex class I-restricted fashion. As few as 100 infectious units of virus induced a strong CTL response. Induction of CTL by SFV-NP could also be achieved in CD4 gene-targeted mice, demonstrating the independence of the primary CTL response of CD4+ helper T cells. One immunization generated a CTL response that peaked after 1 week, and an additional booster injection generated a CTL memory, which was still detectable after 40 days. SFV-NP immunizations also generated high-titered IgG humoral responses that remained significant after several months. These results demonstrate that the recombinant SFV suicide system is highly efficient in antigen presentation and suggest that it may have a potential as a recombinant vaccine.
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Engineered saRNA vaccines rely on the insertion of the gene encoding the target antigen into the genome of an RNA virus (mainly alphavirus) as well as the use of its replication machinery to amplify the delivered RNA, thereby increasing antigen expression.
“Engineered saRNA vaccines rely on the insertion of the gene encoding the target antigen into the genome of an RNA virus (mainly alphavirus) as well as the use of its replication machinery to amplify the delivered RNA, thereby increasing antigen expression.191–193”
From Advances in COVID-19 mRNA vaccine development (2022) · cites this paper as [191]
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Self-citation
- Authors
- Zhou, X., Berglund, P., Zhao, H., Liljeström, P., & Jondal, M.
- Affiliations
- Karolinska Institutet (SE)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1995-03-28
- Volume
- 92
- Issue
- 7
- Pages
- 3009-3013
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC42348
- OpenAlex
- W2083689618
- Cited by
- 115
- References
- 50
- Citations by year
- 2023: 1 · 2022: 1 · 2021: 2 · 2020: 2 · 2019: 2 · 2018: 1 · 2017: 2 · 2015: 1 · 2014: 5 · 2013: 2
- FWCI
- 8.62
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Epidemiology › Influenza Virus Research Studies
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Health Sciences › Medicine › Epidemiology › Virology and Viral Diseases
- Keywords
- Semliki Forest virus, recombinant virus vectors, influenza virus nucleoprotein, CD8+ cytotoxic T lymphocytes, CTL priming, MHC class I restriction, humoral immune response, IgG, booster vaccination, antigen presentation, recombinant vaccine
- MeSH terms
- Amino Acid Sequence, Animals, Antibody Formation, Cytotoxicity, Immunologic, H-2 Antigens, Immunologic Memory, Melanoma, Experimental, Mice, Inbred BALB C, Mice, Inbred C57BL, Molecular Sequence Data, Oligopeptides, Influenza A virus, Recombination, Genetic, Semliki forest virus, T-Lymphocytes, Cytotoxic, Thymoma, Thymus Neoplasms, Tumor Cells, Cultured, Vaccines, Synthetic, Viral Vaccines, Virus Replication, CD8-Positive T-Lymphocytes, Mice
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