Enhancing Anti-G Antibody Induction by a Live Single-Cycle Prefusion F—Expressing RSV Vaccine Improves In Vitro and In Vivo Efficacy
The human respiratory syncytial virus (RSV) is a major cause of severe respiratory tract disease, and a vaccine is not available. We previously reported a novel live vaccine expressing prefusion-stabilized fusion protein (preF) in place of the native F protein (RSV-preF<sup>ΔCT</sup>). A...
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MDPI AG
2022-11-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/14/11/2474 |
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| author | Pramila Lamichhane Megolhubino Terhüja Timothy A. Snider Antonius G. P. Oomens |
| author_facet | Pramila Lamichhane Megolhubino Terhüja Timothy A. Snider Antonius G. P. Oomens |
| author_sort | Pramila Lamichhane |
| collection | DOAJ |
| description | The human respiratory syncytial virus (RSV) is a major cause of severe respiratory tract disease, and a vaccine is not available. We previously reported a novel live vaccine expressing prefusion-stabilized fusion protein (preF) in place of the native F protein (RSV-preF<sup>ΔCT</sup>). As preF is non-functional, RSV-preF<sup>ΔCT</sup> was amplified in a production line expressing a functional substitute, and exhibited a single-cycle replication phenotype, which holds several unique potential advantages. RSV-preF<sup>ΔCT</sup> prevented shedding and lung pathology after viral challenge in mice, but induced low levels of anti-attachment protein (G) antibodies (Abs). Given the significant contributions of anti-G Abs toward disease prevention, we generated modifications to RSV-preF<sup>ΔCT</sup> in an effort to induce higher anti-G Ab levels. The Ab levels were monitored after the prime-boost vaccination of mice with modified vaccines. The most successful modification for enhancing induced anti-G Abs was seen with the placement of G in the first genome position. This vaccine also reduced the pathology after challenge with a high dose of wt RSV, and outperformed the sera from wt RSV-vaccinated mice in in vitro neutralization. Thus, raising the anti-G Ab levels induced by RSV-preF<sup>ΔCT</sup> enhanced efficacy in vitro and in vivo, and constitutes an important next step in developing a live, single-cycle, efficacious vaccine for the human population. |
| first_indexed | 2024-03-09T18:34:47Z |
| format | Article |
| id | doaj.art-ed2f27ae83364b06a18751886b477b92 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-09T18:34:47Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-ed2f27ae83364b06a18751886b477b922023-11-24T07:17:48ZengMDPI AGViruses1999-49152022-11-011411247410.3390/v14112474Enhancing Anti-G Antibody Induction by a Live Single-Cycle Prefusion F—Expressing RSV Vaccine Improves In Vitro and In Vivo EfficacyPramila Lamichhane0Megolhubino Terhüja1Timothy A. Snider2Antonius G. P. Oomens3Department of Veterinary Pathobiology, College of Veterinary Medicine, Oklahoma State University, Stillwater, OK 74078, USADepartment of Veterinary Pathobiology, College of Veterinary Medicine, Oklahoma State University, Stillwater, OK 74078, USADepartment of Veterinary Pathobiology, College of Veterinary Medicine, Oklahoma State University, Stillwater, OK 74078, USADepartment of Veterinary Pathobiology, College of Veterinary Medicine, Oklahoma State University, Stillwater, OK 74078, USAThe human respiratory syncytial virus (RSV) is a major cause of severe respiratory tract disease, and a vaccine is not available. We previously reported a novel live vaccine expressing prefusion-stabilized fusion protein (preF) in place of the native F protein (RSV-preF<sup>ΔCT</sup>). As preF is non-functional, RSV-preF<sup>ΔCT</sup> was amplified in a production line expressing a functional substitute, and exhibited a single-cycle replication phenotype, which holds several unique potential advantages. RSV-preF<sup>ΔCT</sup> prevented shedding and lung pathology after viral challenge in mice, but induced low levels of anti-attachment protein (G) antibodies (Abs). Given the significant contributions of anti-G Abs toward disease prevention, we generated modifications to RSV-preF<sup>ΔCT</sup> in an effort to induce higher anti-G Ab levels. The Ab levels were monitored after the prime-boost vaccination of mice with modified vaccines. The most successful modification for enhancing induced anti-G Abs was seen with the placement of G in the first genome position. This vaccine also reduced the pathology after challenge with a high dose of wt RSV, and outperformed the sera from wt RSV-vaccinated mice in in vitro neutralization. Thus, raising the anti-G Ab levels induced by RSV-preF<sup>ΔCT</sup> enhanced efficacy in vitro and in vivo, and constitutes an important next step in developing a live, single-cycle, efficacious vaccine for the human population.https://www.mdpi.com/1999-4915/14/11/2474respiratory syncytial virusRSVvaccineattachment proteinG proteinprefusion F |
| spellingShingle | Pramila Lamichhane Megolhubino Terhüja Timothy A. Snider Antonius G. P. Oomens Enhancing Anti-G Antibody Induction by a Live Single-Cycle Prefusion F—Expressing RSV Vaccine Improves In Vitro and In Vivo Efficacy Viruses respiratory syncytial virus RSV vaccine attachment protein G protein prefusion F |
| title | Enhancing Anti-G Antibody Induction by a Live Single-Cycle Prefusion F—Expressing RSV Vaccine Improves In Vitro and In Vivo Efficacy |
| title_full | Enhancing Anti-G Antibody Induction by a Live Single-Cycle Prefusion F—Expressing RSV Vaccine Improves In Vitro and In Vivo Efficacy |
| title_fullStr | Enhancing Anti-G Antibody Induction by a Live Single-Cycle Prefusion F—Expressing RSV Vaccine Improves In Vitro and In Vivo Efficacy |
| title_full_unstemmed | Enhancing Anti-G Antibody Induction by a Live Single-Cycle Prefusion F—Expressing RSV Vaccine Improves In Vitro and In Vivo Efficacy |
| title_short | Enhancing Anti-G Antibody Induction by a Live Single-Cycle Prefusion F—Expressing RSV Vaccine Improves In Vitro and In Vivo Efficacy |
| title_sort | enhancing anti g antibody induction by a live single cycle prefusion f expressing rsv vaccine improves in vitro and in vivo efficacy |
| topic | respiratory syncytial virus RSV vaccine attachment protein G protein prefusion F |
| url | https://www.mdpi.com/1999-4915/14/11/2474 |
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