A novel platform for engineered AAV-based vaccines
Engineering of adeno-associated virus (AAV) capsids allowed for the development of gene therapy vectors with improved tropism and enhanced transduction efficiency. Capsid engineering can also be used to adapt the AAV technology for applications outside gene therapy. Here, we investigated modified AA...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-03-01
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| Series: | Molecular Therapy: Methods & Clinical Development |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2329050125000130 |
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| author | Sabrina Babutzka Miranda Gehrke Anastasia Papadopoulou Maria Diedrichs-Möhring Maria Giannaki Lena Hennis Bastian Föhr Cale Kooyman Andreas Osterman Evangelia Yannaki Gerhild Wildner Hermann Ammer Stylianos Michalakis |
| author_facet | Sabrina Babutzka Miranda Gehrke Anastasia Papadopoulou Maria Diedrichs-Möhring Maria Giannaki Lena Hennis Bastian Föhr Cale Kooyman Andreas Osterman Evangelia Yannaki Gerhild Wildner Hermann Ammer Stylianos Michalakis |
| author_sort | Sabrina Babutzka |
| collection | DOAJ |
| description | Engineering of adeno-associated virus (AAV) capsids allowed for the development of gene therapy vectors with improved tropism and enhanced transduction efficiency. Capsid engineering can also be used to adapt the AAV technology for applications outside gene therapy. Here, we investigated modified AAV capsids as scaffolds for the presentation of large immunogenic antigens to elicit a strong and specific immune response against pathogens. Using SARS-CoV-2 as a model pathogen, we introduced ∼200 amino acids of the SARS-CoV-2 receptor-binding domain (RBD) into a surface-exposed variable loop region of AAV2 and AAV9, resulting in AAV2.RBD and AAV9.RBD capsids (AAV.RBDs). This engineering endowed AAV.RBDs with SARS-CoV-2-like properties, such as angiotensin-converting enzyme 2 receptor affinity. In line with this, AAV.RBDs were neutralized by sera from human donors vaccinated against SARS-CoV-2. When administered subcutaneously to rabbits, AAV.RBDs elicited a strong humoral response against SARS-CoV-2 RBD. Moreover, the AAV.RBDs were able to trigger RBD-specific cellular immune responses in peripheral human lymphocytes. In conclusion, this novel AAV-based next-generation vaccine platform allows for the presentation of large antigenic sequences to elicit strong and specific immune responses. This versatile vaccine technology could be explored in the context of diseases where conventional immunization approaches have been unsuccessful. |
| format | Article |
| id | doaj-art-28eb26d98e2345e7a929d395cc92c1fc |
| institution | Kabale University |
| issn | 2329-0501 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Methods & Clinical Development |
| spelling | doaj-art-28eb26d98e2345e7a929d395cc92c1fc2025-02-09T05:00:34ZengElsevierMolecular Therapy: Methods & Clinical Development2329-05012025-03-01331101418A novel platform for engineered AAV-based vaccinesSabrina Babutzka0Miranda Gehrke1Anastasia Papadopoulou2Maria Diedrichs-Möhring3Maria Giannaki4Lena Hennis5Bastian Föhr6Cale Kooyman7Andreas Osterman8Evangelia Yannaki9Gerhild Wildner10Hermann Ammer11Stylianos Michalakis12Department of Ophthalmology, University Hospital, LMU Munich, 80336 Munich, GermanyDepartment of Ophthalmology, University Hospital, LMU Munich, 80336 Munich, GermanyHematology Department-Hematopoietic Cell Transplantation Unit, Gene and Cell Therapy Center, “George Papanikolaou” Hospital, 570 10 Thessaloniki, GreeceDepartment of Ophthalmology, University Hospital, LMU Munich, 80336 Munich, GermanyHematology Department-Hematopoietic Cell Transplantation Unit, Gene and Cell Therapy Center, “George Papanikolaou” Hospital, 570 10 Thessaloniki, GreeceDepartment of Ophthalmology, University Hospital, LMU Munich, 80336 Munich, GermanyDepartment of Ophthalmology, University Hospital, LMU Munich, 80336 Munich, GermanyDepartment of Ophthalmology, University Hospital, LMU Munich, 80336 Munich, GermanyMax Von Pettenkofer Institute and Gene Center, Virology, LMU Munich, 80336 Munich, GermanyHematology Department-Hematopoietic Cell Transplantation Unit, Gene and Cell Therapy Center, “George Papanikolaou” Hospital, 570 10 Thessaloniki, Greece; Department of Medicine, University of Washington, Seattle, WA 91895, USADepartment of Ophthalmology, University Hospital, LMU Munich, 80336 Munich, Germany; Corresponding author: Gerhild Wildner, Department of Ophthalmology, University Hospital, LMU Munich, 80336 Munich, Germany.Department of Veterinary Sciences, Ludwig-Maximilians-Universität München, 80539 Munich, GermanyDepartment of Ophthalmology, University Hospital, LMU Munich, 80336 Munich, Germany; Corresponding author: Stylianos Michalakis, Department of Ophthalmology, University Hospital, LMU Munich, 80336 Munich, Germany.Engineering of adeno-associated virus (AAV) capsids allowed for the development of gene therapy vectors with improved tropism and enhanced transduction efficiency. Capsid engineering can also be used to adapt the AAV technology for applications outside gene therapy. Here, we investigated modified AAV capsids as scaffolds for the presentation of large immunogenic antigens to elicit a strong and specific immune response against pathogens. Using SARS-CoV-2 as a model pathogen, we introduced ∼200 amino acids of the SARS-CoV-2 receptor-binding domain (RBD) into a surface-exposed variable loop region of AAV2 and AAV9, resulting in AAV2.RBD and AAV9.RBD capsids (AAV.RBDs). This engineering endowed AAV.RBDs with SARS-CoV-2-like properties, such as angiotensin-converting enzyme 2 receptor affinity. In line with this, AAV.RBDs were neutralized by sera from human donors vaccinated against SARS-CoV-2. When administered subcutaneously to rabbits, AAV.RBDs elicited a strong humoral response against SARS-CoV-2 RBD. Moreover, the AAV.RBDs were able to trigger RBD-specific cellular immune responses in peripheral human lymphocytes. In conclusion, this novel AAV-based next-generation vaccine platform allows for the presentation of large antigenic sequences to elicit strong and specific immune responses. This versatile vaccine technology could be explored in the context of diseases where conventional immunization approaches have been unsuccessful.http://www.sciencedirect.com/science/article/pii/S2329050125000130AAVcapsidengineered capsidvaccinevirus-like particlesprotein carrier |
| spellingShingle | Sabrina Babutzka Miranda Gehrke Anastasia Papadopoulou Maria Diedrichs-Möhring Maria Giannaki Lena Hennis Bastian Föhr Cale Kooyman Andreas Osterman Evangelia Yannaki Gerhild Wildner Hermann Ammer Stylianos Michalakis A novel platform for engineered AAV-based vaccines Molecular Therapy: Methods & Clinical Development AAV capsid engineered capsid vaccine virus-like particles protein carrier |
| title | A novel platform for engineered AAV-based vaccines |
| title_full | A novel platform for engineered AAV-based vaccines |
| title_fullStr | A novel platform for engineered AAV-based vaccines |
| title_full_unstemmed | A novel platform for engineered AAV-based vaccines |
| title_short | A novel platform for engineered AAV-based vaccines |
| title_sort | novel platform for engineered aav based vaccines |
| topic | AAV capsid engineered capsid vaccine virus-like particles protein carrier |
| url | http://www.sciencedirect.com/science/article/pii/S2329050125000130 |
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