Immunize and disappear—Safety-optimized mRNA vaccination with a panel of 29 allergens
Abstract
Background The spread of type I allergic diseases has reached epidemic dimensions. The success of therapeutic intervention is limited, and hence prophylactic vaccination is now seriously considered. However, immunization of healthy individuals requires safety standards far beyond those applicable for therapeutic approaches. mRNAs encoding allergen molecules represent an attractive tool for preventive vaccination because of the inherent safety features of this vaccine type.Objective In the current study we investigated whether mRNA constructs would be capable of protecting against type I allergic reactions in a murine model using the grass pollen allergen Phl p 5 and 28 other major pollen, food, animal, mold, and latex allergens.Methods BALB/c mice were immunized intradermally either with conventional or replicase-based mRNA constructs. Subsequently, animals were sensitized by means of subcutaneous injection of allergen/alum, followed by airway provocation. IgG1/IgG2a/IgE titers were determined by using ELISAs. Allergen-specific functional IgE levels were assessed by using the basophil release assay. Measurement of cytokines in splenocyte cultures and bronchoalveolar lavage fluids were performed by using enzyme-linked immunosorbent spot assays/sandwich ELISAs. Eosinophil and CD8(+) counts in bronchoalveolar lavage specimens were determined by means of flow cytometry. Airway hyperreactivity was assessed with whole-body plethysmography and invasive resistance/dynamic compliance measurement.Results mRNA vaccination proved its antiallergic efficacy in terms of IgG subclass distribution, functional IgE suppression, reduction of IL-4 and IL-5 levels, induction of IFN-gamma-producing cells, and reduction of airway hyperreactivity and eosinophil counts in the lung.Conclusion Immunization with mRNA induces T(H)1-biased immune responses similar to those elicited through DNA-based vaccination but additionally offers the advantage of a superior safety profile.
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The translation efficacy of mRNA encoding luciferase begins to decrease after 8 days or 16 days when stored RNase free at room temperature as a liquid or in a lyophilized form, respectively.
“In 2009, Roesler et al. show that the translation efficacy of mRNA encoding luciferase begins to decrease after 8 days or 16 days when stored –RNAse free– at room temperature as a liquid or in a lyophilized form, respectively.”
From mRNA-lipid nanoparticle COVID-19 vaccines: structure and stability (2021) · cites this paper as Roesler et al., 2009
Cites
Exposure to farming in early life and development of asthma and allergy: a cross-sectional survey
Riedler, J., Braun-Fahrländer, C., Eder, W., Schreuer, M., Waser, M., Maisch, S., Carr, D., Schierl, R., Nowak, D., & von Mutius, E. (2001) · The Lancet · doi:10.1016/s0140-6736(01)06252-3 · Cited by 1,520 · see citing works
Noninvasive Measurement of Airway Responsiveness in Allergic Mice Using Barometric Plethysmography
Hamelmann, E. H., Schwarze, J., Takeda, K., Oshiba, A., Larsen, G. L., Irvin, C. G., & Gelfand, E. W. (1997) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.156.3.9606031 · Cited by 1,286 · see citing works
Competence and competition: the challenge of becoming a long-lived plasma cell
Radbruch, A., Muehlinghaus, G., Luger, E., Inamine, A., Smith, K. G. C., Dörner, T., & Hiepe, F. (2006) · Nature reviews. Immunology · doi:10.1038/nri1886 · Cited by 1,033 · see citing works
Measles and atopy in Guinea-Bissau
Shaheen, S. O., BARKER, D. J. P., Heyes, C., Shiell, A. W., Aaby, P., Hall, A. J., & Goudiaby, A. (1996) · The Lancet · doi:10.1016/s0140-6736(96)91617-7 · Cited by 580 · see citing works
Exposure to endotoxin or other bacterial components might protect against the development of atopy
Mutius, V., Braun‐Fahrländer, Schierl, Riedler, Ehlermann, Maisch, Waser, & Nowak (2000) · Clinical & Experimental Allergy · doi:10.1046/j.1365-2222.2000.00959.x · Cited by 579 · see citing works
Immunologic influences on allergy and the TH1/TH2 balance
Romagnani, S. (2004) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2003.11.025 · Cited by 463 · see citing works
Bousquet, P., Chinn, S., Janson, C., Kogevinas, M., Burney, P., & Jarvis, D. (2007) · Allergy · doi:10.1111/j.1398-9995.2006.01293.x · Cited by 406 · 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
Prevalence of Atopy and Pollinosis in the Adult Population of Switzerland (SAPALDIA Study)
Wüthrich, B., Schindler, C., Leuenberger, P., & Ackermann-Liebrich, U. (2009) · International Archives of Allergy and Immunology · doi:10.1159/000236836 · Cited by 308 · see citing works
Probst, J., Weide, B., Scheel, B., Pichler, B. J., Hoerr, I., Rammensee, H.-G., & Pascolo, S. (2007) · Gene Therapy · doi:10.1038/sj.gt.3302964 · Cited by 206 · see citing works
IL-13 and IFN-γ: Interactions in Lung Inflammation
Ford, J. G., Rennick, D. M., Donaldson, D. D., Venkayya, R., McArthur, C., Hansell, E., Kurup, V. P., Warnock, M. L., & Grünig, G. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.167.3.1769 · Cited by 184 · see citing works
Pascolo, S. (2004) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.4.8.1285 · Cited by 152 · see citing works
Renz, H. E., Lack, G., Saloga, J., et al. (1994) · The Journal of Immunology · doi:10.4049/jimmunol.152.1.351 · Cited by 150 · see citing works
Polarization of immunity induced by direct injection of naked sequence-stabilized mRNA vaccines
Carralot, J.-P., Probst, J., Hoerr, I., Scheel, B., Teufel, R., Jung, G., Rammensee, H.-G., & Pascolo, S. (2004) · Cellular and Molecular Life Sciences CMLS · doi:10.1007/s00018-004-4255-0 · Cited by 149 · see citing works
Ball, T., Sperr, W. R., Valent, P., Lidholm, J., Spitzauer, S., Ebner, C., Kraft, D., & Valenta, R. (1999) · European Journal of Immunology · doi:10.1002/(sici)1521-4141(199906)29:06 · Cited by 141 · see citing works
Molecular Genetics of Allergic Diseases
Ono, S. J. (2000) · Annual Review of Immunology · doi:10.1146/annurev.immunol.18.1.347 · Cited by 120 · see citing works
van Ree, R., LEEUWEN, W. A. V., Dieges, P. H., van Wijk, R. G., de Jong, N. W., BREWCZYSKI, P. Z., Kroon, A. M., Schilte, P. P. M., Tan, K. Y., SIMON‐LICHT, I. F., et al. (1997) · Clinical & Experimental Allergy · doi:10.1046/j.1365-2222.1997.d01-416.x · Cited by 100 · see citing works
Apoptosis is essential for the increased efficacy of alphaviral replicase-based DNA vaccines
Leitner, W. W., Hwang, L. N., Bergmann‐Leitner, E. S., Finkelstein, S. E., Frank, S., & Restifo, N. P. (2003) · Vaccine · doi:10.1016/j.vaccine.2003.10.013 · Cited by 77 · see citing works
Replicon-based vectors of positive strand RNA viruses.
Khromykh, A. A. (2000) · PubMed · Cited by 66 · see citing works
Wells, J. W., Cowled, C. J., Giorgini, A., Kemeny, D. M., & Noble, A. (2006) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2006.09.004 · Cited by 57 · see citing works
Antigen‐specific CD8+ T cells inhibit IgE responses and interleukin‐4 production by CD4+ T cells
Holmes, B. J., MacAry, P. A., Noble, A., et al. (1997) · European Journal of Immunology · doi:10.1002/eji.1830271027 · Cited by 57 · see citing works
Slater, J. E., Paupore, E. J., Zhang, Y. T., & Colberg‐Poley, A. M. (1998) · Journal of Allergy and Clinical Immunology · doi:10.1016/s0091-6749(98)70137-x · Cited by 53 · see citing works
Hochreiter, R., Stepanoska, T., Ferreira, F., et al. (2003) · European Journal of Immunology · doi:10.1002/eji.200323377 · Cited by 48 · see citing works
Self-citationBauer, R., Scheiblhofer, S., Kern, K., et al. (2006) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2006.03.033 · Cited by 41 · see citing works
Self-citationDNA vaccines for allergy treatment
Hartl, A. J., Weiss, R., Hochreiter, R., et al. (2004) · Methods · doi:10.1016/j.ymeth.2003.08.014 · Cited by 39 · see citing works
Self-citationIs Genetic Vaccination against Allergy Possible?
Weiss, R., Scheiblhofer, S., Gabler, M., Ferreira, F., Leitner, W. W., & Thalhamer, J. (2006) · International Archives of Allergy and Immunology · doi:10.1159/000091946 · Cited by 33 · see citing works
Self-citationUpregulation of Interleukin-4 Receptor by Interferon-γ
Yamamoto, S., Kobayashi, I., Tsuji, K., Nishi, N., Muro, E., Miyazaki, M., Zaitsu, M., Inada, S., Ichimaru, T., & Hamasaki, Y. (2004) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2004-0128oc · Cited by 32 · see citing works
Gabler, M., Scheiblhofer, S., Kern, K., et al. (2006) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2006.04.048 · Cited by 32 · see citing works
Self-citationRole of TLR3 in the immunogenicity of replicon plasmid-based vaccines
Diebold, S. S., Schulz, O., Alexopoulou, L., et al. (2008) · Gene Therapy · doi:10.1038/gt.2008.164 · Cited by 28 · see citing works
Finkelman, F. D. (2008) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2007.11.028 · Cited by 26 · see citing works
Inhibition of type I allergic responses with nanogram doses of replicon‐based DNA vaccines
Scheiblhofer, S., Gabler, M., Leitner, W. W., et al. (2006) · Allergy · doi:10.1111/j.1398-9995.2006.01142.x · Cited by 24 · see citing works
Self-citationDNA vaccines: safety aspect assessment and regulation.
Medjitna, T. D. E., Stadler, C., Bruckner, L., et al. (2006) · PubMed · Cited by 21 · see citing works
Scheiblhofer, S., Stoecklinger, A., Guttmann‐Gruber, C., et al. (2006) · Molecular Immunology · doi:10.1016/j.molimm.2006.09.023 · Cited by 19 · see citing works
Self-citationImmune responsiveness, tolerance and dsRNA: implications for traditional paradigms
von Herrath, M. G., & Bot, A. I. (2003) · Trends in Immunology · doi:10.1016/s1471-4906(03)00121-2 · Cited by 15 · see citing works
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mRNA-based therapeutics--developing a new class of drugs
Sahin, U., Karikó, K., & Türeci, Ö. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4278 · Cited by 2,474 · see citing works
mRNA-lipid nanoparticle COVID-19 vaccines: structure and stability
Schoenmaker, L., Witzigmann, D., Kulkarni, J. A., Verbeke, R., Kersten, G., Jiskoot, W., & Crommelin, D. J. A. (2021) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2021.120586 · Cited by 1,566 · see citing works
Tools for translation: non-viral materials for therapeutic mRNA delivery
Hajj, K. A., & Whitehead, K. A. (2017) · Nature Reviews Materials · doi:10.1038/natrevmats.2017.56 · Cited by 799 · see citing works
mRNA as gene therapeutic: How to control protein expression
Tavernier, G., Andries, O., Demeester, J., Sanders, N. N., De Smedt, S. C., & Rejman, J. (2011) · Journal of Controlled Release · doi:10.1016/j.jconrel.2010.10.020 · Cited by 232 · see citing works
Intradermal Electroporation of Naked Replicon RNA Elicits Strong Immune Responses
Johansson, D. X., Ljungberg, K., Kakoulidou, M., & Liljeström, P. (2012) · PLoS ONE · doi:10.1371/journal.pone.0029732 · Cited by 98 · see citing works
mRNA vaccination as a safe approach for specific protection from type I allergy
Weiss, R., Scheiblhofer, S., Roesler, E., Weinberger, E., & Thalhamer, J. (2012) · Expert Review of Vaccines · doi:10.1586/erv.11.168 · Cited by 42 · see citing works
Self-citationAdvancing mRNA technologies for therapies and vaccines: An African context
Kairuz, D., Samudh, N., Ely, A., Arbuthnot, P., & Bloom, K. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1018961 · Cited by 25 · see citing works
- Authors
- Roesler, E., Weiss, R., Weinberger, E. E., Fruehwirth, A., Stoecklinger, A., Mostböck, S., Ferreira, F., Thalhamer, J., & Scheiblhofer, S.
- Affiliations
- University of Salzburg (AT)
- University of Regensburg (DE)
- Corresponding author
- Thalhamer, Josef
- Venue
- Journal of Allergy and Clinical Immunology
- Publisher
- Elsevier BV
- Published
- 2009-11
- Volume
- 124
- Issue
- 5
- Pages
- 1070-1077.e11
- ISSN
- 0091-6749 (ISSN-L)
- OpenAlex
- W1972643355
- Cited by
- 82
- References
- 34
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 5 · 2023: 6 · 2022: 8 · 2021: 7 · 2019: 1 · 2018: 3 · 2017: 1 · 2016: 5 · 2015: 4 · 2014: 3 · 2013: 9 · 2012: 10
- FWCI
- 5.82
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Allergy and Clinical Immunology (publishedVersion)
- PubMed (publishedVersion)
- University of Regensburg Publication Server (University of Regensburg) (acceptedVersion)
- Topics
- Health Sciences › Medicine › Immunology and Allergy › Allergic Rhinitis and Sensitization
- Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
- Health Sciences › Medicine › Immunology and Allergy › Food Allergy and Anaphylaxis Research
- Keywords
- mRNA vaccination, allergen immunization, immediate hypersensitivity, allergic diseases, Phl p 5, grass pollen allergens, allergen panel, intradermal vaccination, airway hyperresponsiveness, eosinophils, Th1 response, interferon-gamma, vaccine safety
- MeSH terms
- Allergens, Animals, Bronchoalveolar Lavage Fluid, Female, Hypersensitivity, Immunoglobulin E, Immunoglobulin G, Injections, Intradermal, Mice, Inbred BALB C, RNA, Messenger, Vaccination, Vaccines, Cytokines, Mice
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