Gene Expression Driven by a Strong Viral Promoter in MVA Increases Vaccination Efficiency by Enhancing Antibody Responses and Unmasking CD8⁺ T Cell Epitopes.
Average rating
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Star rating
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Authors
Becker, Pablo DNörder, Miriam
Weissmann, Sebastian
Ljapoci, Ronny
Erfle, Volker
Drexler, Ingo
Guzmán, Carlos Alberto
Issue Date
2014-07-22
Metadata
Show full item recordAbstract
Viral vectors are promising tools for vaccination strategies and immunotherapies. However, CD8⁺ T cell responses against pathogen-derived epitopes are usually limited to dominant epitopes and antibody responses to recombinant encoded antigens (Ags) are mostly weak. We have previously demonstrated that the timing of viral Ag expression in infected professional Ag-presenting cells strongly shapes the epitope immunodominance hierarchy. T cells recognizing determinants derived from late viral proteins have a clear disadvantage to proliferate during secondary responses. In this work we evaluate the effect of overexpressing the recombinant Ag using the modified vaccinia virus early/late promoter H5 (mPH5). Although the Ag-expression from the natural promoter 7.5 (P7.5) and the mPH5 seemed similar, detailed analysis showed that mPH5 not only induces higher expression levels than P7.5 during early phase of infection, but also Ag turnover is enhanced. The strong overexpression during the early phase leads to broader CD8 T cell responses, while preserving the priming efficiency of stable Ags. Moreover, the increase in Ag-secretion favors the induction of strong antibody responses. Our findings provide the rationale to develop new strategies for fine-tuning the responses elicited by recombinant modified vaccinia virus Ankara by using selected promoters to improve the performance of this viral vector.Citation
Gene Expression Driven by a Strong Viral Promoter in MVA Increases Vaccination Efficiency by Enhancing Antibody Responses and Unmasking CD8⁺ T Cell Epitopes. 2014, 2 (3):581-600 Vaccines (Basel)Affiliation
Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.Journal
VaccinesPubMed ID
26344747Type
ArticleLanguage
enISSN
2076-393Xae974a485f413a2113503eed53cd6c53
10.3390/vaccines2030581
Scopus Count
The following license files are associated with this item:
- Creative Commons
Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by-nc-sa/4.0/
Related articles
- Analysis of MHC Class I Processing Pathways That Generate a Response to Vaccinia Virus Late Proteins.
- Authors: Niu TK, Princiotta MF, Sei JJ, Norbury CC
- Issue date: 2019 Dec 2
- Potent Anti-hepatitis C Virus (HCV) T Cell Immune Responses Induced in Mice Vaccinated with DNA-Launched RNA Replicons and Modified Vaccinia Virus Ankara-HCV.
- Authors: Marín MQ, Pérez P, Ljungberg K, Sorzano CÓS, Gómez CE, Liljeström P, Esteban M, García-Arriaza J
- Issue date: 2019 Apr 1
- Modified Vaccinia Virus Ankara Can Induce Optimal CD8(+) T Cell Responses to Directly Primed Antigens Depending on Vaccine Design.
- Authors: Wong YC, Croft S, Smith SA, Lin LCW, Cukalac T, La Gruta NL, Drexler I, Tscharke DC
- Issue date: 2019 Nov 1
- Removal of the C6 Vaccinia Virus Interferon-β Inhibitor in the Hepatitis C Vaccine Candidate MVA-HCV Elicited in Mice High Immunogenicity in Spite of Reduced Host Gene Expression.
- Authors: Marín MQ, Pérez P, Gómez CE, Sorzano CÓS, Esteban M, García-Arriaza J
- Issue date: 2018 Aug 8
- Immunisation of cattle against Babesia bovis combining a multi-epitope modified vaccinia Ankara virus and a recombinant protein induce strong Th1 cell responses but fails to trigger neutralising antibodies required for protection.
- Authors: Jaramillo Ortiz JM, Paoletta MS, Gravisaco MJ, López Arias LS, Montenegro VN, de la Fournière SAM, Valenzano MN, Guillemi EC, Valentini B, Echaide I, Farber MD, Wilkowsky SE
- Issue date: 2019 Oct