Mimicking live flavivirus immunization with a noninfectious RNA vaccine
Open accessAbstract
Flaviviruses are human pathogens of world-wide medical importance. They have recently received much additional attention because of their spread to new regions (such as West Nile virus to North America), highlighting their potential as newly emerging disease agents. Using tick-borne encephalitis virus, we have developed and evaluated in mice a new genetic vaccine based on self-replicating but noninfectious RNA. This RNA contains all of the necessary genetic information for establishing its replication machinery in the host cell, thus mimicking a natural infection. However, genetic modifications in the region encoding the capsid protein simultaneously prevent the assembly of infectious virus particles and promote the secretion of noninfectious subviral particles that elicit neutralizing antibodies. These characteristics demonstrate that a new generation of flavivirus vaccines can be designed that stimulate the same spectrum of innate and specific immune responses as a live vaccine but have the safety features of an inactivated vaccine.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Recombinant viral vector technologies have the advantage of efficient delivery of the nucleic acid payload, but their utility is often hampered by antivector immunity, production limitations, and safety concerns.
“Recombinant viral vector technologies have the advantage of efficient delivery of the nucleic acid payload, but their utility is often hampered by antivector immunity, production limitations, and safety concerns (3,4).”
From Nonviral delivery of self-amplifying RNA vaccines (2012) · cites this paper as [3]
There are limited published data on the in vivo delivery of self-amplifying RNA using nonviral delivery strategies, and none has taken advantage of the recently developed, clinically suitable delivery systems for siRNA.
“There are limited published data on the in vivo delivery of self-amplifying RNA using nonviral delivery strategies (3,14,18), and none has taken advantage of the recently developed, clinically suitable delivery systems for siRNA (19,20).”
From Nonviral delivery of self-amplifying RNA vaccines (2012) · cites this paper as [3]
Cites
Maturation of the head of bacteriophage T4
Laemmli, U. K., & Fãvre, M. (1973) · Journal of Molecular Biology · doi:10.1016/0022-2836(73)90198-8 · Cited by 3,725 · see citing works
Antibodies, viruses and vaccines
Burton, D. R. (2002) · Nature Reviews Immunology · doi:10.1038/nri891 · Cited by 637 · see citing works
Structures of immature flavivirus particles
Zhang, W., Corver, J., Chipman, P. R., et al. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg270 · Cited by 500 · see citing works
Liu, M. A. (2003) · Journal of Internal Medicine · doi:10.1046/j.1365-2796.2003.01140.x · Cited by 346 · see citing works
Cancer therapy using a self-replicating RNA vaccine
Han, Y., Zaks, T. Z., Wang, R., Irvine, K. R., Kammula, U. S., Marincola, F. M., Leitner, W. W., & Restifo, N. P. (1999) · Nature Medicine · doi:10.1038/10548 · Cited by 322 · see citing works
Alphavirus-based DNA vaccine breaks immunological tolerance by activating innate antiviral pathways
Leitner, W. W., Hwang, L. N., DeVeer, M., Zhou, A., Silverman, R. H., Williams, B. R. G., Dubensky, T. W., Han, Y., & Restifo, N. P. (2002) · Nature Medicine · doi:10.1038/nm813 · Cited by 269 · see citing works
Heinz, F. X., Stiasny, K., Püschner-Auer, G., et al. (1994) · Virology · doi:10.1006/viro.1994.1013 · Cited by 262 · see citing works
Self-citationMolecular Organization of a Recombinant Subviral Particle from Tick-Borne Encephalitis Virus
Ferlenghi, I., Clarke, M., Ruttan, T., Allison, S. L., Schalich, J., Heinz, F. X., Harrison, S. C., Rey, F. A., & Fuller, S. D. (2001) · Molecular Cell · doi:10.1016/s1097-2765(01)00206-4 · Cited by 261 · see citing works
Self-citationMonath, T. P. C., Guirakhoo, F., Nichols, R., Yoksan, S., Schrader, R., Murphy, C., Blum, P. S., Woodward, S., McCarthy, K., Mathis, D., et al. (2003) · The Journal of Infectious Diseases · doi:10.1086/378356 · Cited by 218 · see citing works
Mandl, C. W., Holzmann, H., Meixner, T., et al. (1998) · Journal of Virology · doi:10.1128/jvi.72.3.2132-2140.1998 · Cited by 213 · see citing works
Self-citationSchlesinger, J. J., BRANDRISS, M. W., Cropp, C. B., et al. (1986) · Journal of Virology · doi:10.1128/jvi.60.3.1153-1155.1986 · Cited by 210 · see citing works
Schalich, J., Allison, S. L., Stiasny, K., et al. (1996) · Journal of Virology · doi:10.1128/jvi.70.7.4549-4557.1996 · Cited by 205 · see citing works
Self-citationFlavivirus Capsid Is a Dimeric Alpha-Helical Protein
Jones, C. T., Ma, L., Burgner, J. W., et al. (2003) · Journal of Virology · doi:10.1128/jvi.77.12.7143-7149.2003 · Cited by 196 · see citing works
Structures and mechanisms in flavivirus fusion
Heinz, F. X., & Allison, S. L. (2000) · Advances in virus research · doi:10.1016/s0065-3527(00)55005-2 · Cited by 185 · see citing works
Self-citationHeinz, F. X., Berger, R., Tuma, W., et al. (1983) · Virology · doi:10.1016/s0042-6822(83)80010-5 · Cited by 165 · see citing works
Self-citationGuirakhoo, F., Heinz, F. X., & Künz, C. (1989) · Virology · doi:10.1016/0042-6822(89)90044-5 · Cited by 146 · see citing works
Self-citationStocks, C. E., & Lobigs, M. (1998) · Journal of Virology · doi:10.1128/jvi.72.3.2141-2149.1998 · Cited by 146 · see citing works
Mandl, C. W., Heinz, F.-X., Holzmann, H., et al. (1997) · Journal of General Virology · doi:10.1099/0022-1317-78-5-1049 · Cited by 138 · see citing works
Self-citationKofler, R. M., Heinz, F. X., & Mandl, C. W. (2002) · Journal of Virology · doi:10.1128/jvi.76.7.3534-3543.2002 · Cited by 135 · see citing works
Self-citationIn vitro-synthesized infectious RNA as an attenuated live vaccine in a flavivirus model
Mandl, C. W., Aberle, J. H., Aberle, S. W., Holzmann, H., Allison, S. L., & Heinz, F. X. (1998) · Nature Medicine · doi:10.1038/4031 · Cited by 124 · see citing works
Self-citationGehrke, R., Ecker, M., Aberle, S. W., et al. (2003) · Journal of Virology · doi:10.1128/jvi.77.16.8924-8933.2003 · Cited by 109 · see citing works
Self-citationHeinz, F. X., Allison, S. L., Stiasny, K., Schalich, J., Holzmann, H., Mandl, C. W., & Künz, C. (1995) · Vaccine · doi:10.1016/0264-410x(95)00133-l · Cited by 107 · see citing works
Self-citationHall, R. A., Nisbet, D. J., Pham, K. B., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1834270100 · Cited by 107 · see citing works
Jacobs, S. C., Stephenson, J. R., & Wilkinson, G. W. G. (1992) · Journal of Virology · doi:10.1128/jvi.66.4.2086-2095.1992 · Cited by 97 · see citing works
Aberle, J. H., Aberle, S. W., Allison, S. L., et al. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.163.12.6756 · Cited by 90 · see citing works
Self-citationWallner, G., Mandl, C. W., Ecker, M., et al. (1996) · Journal of General Virology · doi:10.1099/0022-1317-77-5-1035 · Cited by 86 · see citing works
Self-citationLee, E., Stocks, C. E., Amberg, S. M., et al. (2000) · Journal of Virology · doi:10.1128/jvi.74.1.24-32.2000 · Cited by 81 · see citing works
Traditional and novel approaches to flavivirus vaccines
Pugachev, K. V., Guirakhoo, F., Trent, D. W., et al. (2003) · International Journal for Parasitology · doi:10.1016/s0020-7519(03)00063-8 · Cited by 79 · see citing works
Lobigs, M., Arthur, C. E., Müllbacher, A., et al. (1994) · Virology · doi:10.1006/viro.1994.1335 · Cited by 78 · see citing works
Kreil, T. R., Maier, E., Fraiss, S., & Eibl, M. M. (1998) · Journal of Virology · doi:10.1128/jvi.72.4.3076-3081.1998 · Cited by 76 · see citing works
Kunjin Virus Replicon Vaccine Vectors Induce Protective CD8+T-Cell Immunity
Anraku, I., Harvey, T. J., Linedale, R., Gardner, J., Harrich, D., Suhrbier, A., & Khromykh, A. A. (2002) · Journal of Virology · doi:10.1128/jvi.76.8.3791-3799.2002 · Cited by 76 · see citing works
Kofler, R. M., Leitner, A., O'Ríordáin, G., et al. (2002) · Journal of Virology · doi:10.1128/jvi.77.1.443-451.2003 · Cited by 60 · see citing works
Self-citationHeinz, F.-X., Tuma, W., Guirakhoo, F., et al. (1986) · Journal of Biological Standardization · doi:10.1016/0092-1157(86)90032-6 · Cited by 58 · see citing works
Self-citationKonishi, E., Ajiro, N., Nukuzuma, C., et al. (2003) · Vaccine · doi:10.1016/s0264-410x(03)00382-7 · Cited by 54 · see citing works
(1999) · PubMed · Cited by 53 · see citing works
Holzmann, H., Stiasny, K., York, H., et al. (1995) · Archives of Virology · doi:10.1007/bf01309857 · Cited by 40 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
mRNA vaccines — a new era in vaccinology
Pardi, N., Hogan, M. J., Porter, F. W., & Weissman, D. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2017.243 · Cited by 4,667 · see citing works
Nonviral delivery of self-amplifying RNA vaccines
Geall, A. J., Verma, A., Otten, G. R., Shaw, C. A., Hekele, A., Banerjee, K., Cu, Y., Beard, C. W., Brito, L. A., Krucker, T., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1209367109 · Cited by 675 · see citing works
Self-citationNew Vaccine Technologies to Combat Outbreak Situations
Rauch, S., Jasny, E., Schmidt, K. E., & Petsch, B. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01963 · Cited by 579 · see citing works
Self-amplifying RNA vaccines for infectious diseases
Bloom, K., van den Berg, F., & Arbuthnot, P. (2021) · Gene Therapy · doi:10.1038/s41434-020-00204-y · Cited by 487 · see citing works
Future of the Particle Replication in Nonwetting Templates (PRINT) Technology
Xu, J., Wong, D. H. C., Byrne, J. D., Chen, K., Bowerman, C., & DeSimone, J. M. (2013) · Angewandte Chemie International Edition · doi:10.1002/anie.201209145 · Cited by 208 · see citing works
Long-term storage of DNA-free RNA for use in vaccine studies
Jones, K. L., Drane, D., & Gowans, E. J. (2007) · BioTechniques · doi:10.2144/000112593 · Cited by 115 · see citing works
Golombek, S., Pilz, M., Steinle, H., Kochba, E., Levin, Y., Lunter, D., Schlensak, C., Wendel, H. P., & Avci-Adali, M. (2018) · Molecular Therapy Nucleic Acids · doi:10.1016/j.omtn.2018.03.005 · Cited by 88 · see citing works
Self-Amplifying RNA Approach for Protein Replacement Therapy
Papukashvili, D., Rcheulishvili, N., Liu, C., Ji, Y., He, Y., & Wang, P. G. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232112884 · Cited by 76 · see citing works
mRNA Vaccines against Flaviviruses
Wollner, C. J., & Richner, J. M. (2021) · Vaccines · doi:10.3390/vaccines9020148 · Cited by 44 · see citing works
- Authors
- Kofler, R. M., Aberle, J. H., Aberle, S. W., Allison, S. L., Heinz, F. X., & Mandl, C. W.
- Affiliations
- Medical University of Vienna (AT)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2004-02-09
- Volume
- 101
- Issue
- 7
- Pages
- 1951-1956
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC357033
- OpenAlex
- W1981821156
- Cited by
- 116
- References
- 36
- Citations by year
- 2025: 1 · 2024: 5 · 2023: 10 · 2022: 5 · 2021: 4 · 2020: 3 · 2019: 2 · 2018: 9 · 2017: 6 · 2016: 5 · 2015: 2 · 2014: 9 · 2013: 8 · 2012: 2
- FWCI
- 6.45
- 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 › Public Health, Environmental and Occupational Health › Mosquito-borne diseases and control
- Health Sciences › Medicine › Infectious Diseases › Viral Infections and Vectors
- Health Sciences › Medicine › Epidemiology › Influenza Virus Research Studies
- Keywords
- flavivirus vaccines, tick-borne encephalitis virus, self-replicating RNA, subviral particles, neutralizing antibodies, innate immune response, emerging viral diseases, West Nile virus
- MeSH terms
- Animals, Antibodies, Viral, Cell Line, Flavivirus, Cricetinae, RNA, Viral, Vaccination, Vaccines, Attenuated, Viral Vaccines, Virion, Gene Deletion, Flavivirus Infections, Capsid Proteins, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review