A Pan-Pneumovirus vaccine based on immunodominant epitopes of the fusion protein
Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) are two leading causes of severe respiratory infections in children, the elderly, and immunocompromised patients. The fusion (F) protein is the major target of neutralizing antibodies. Recent developments in stabilizing the pre-fusio...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.941865/full |
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| author | Jiachen Huang Jiachen Huang Rose J. Miller Rose J. Miller Jarrod J. Mousa Jarrod J. Mousa Jarrod J. Mousa |
| author_facet | Jiachen Huang Jiachen Huang Rose J. Miller Rose J. Miller Jarrod J. Mousa Jarrod J. Mousa Jarrod J. Mousa |
| author_sort | Jiachen Huang |
| collection | DOAJ |
| description | Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) are two leading causes of severe respiratory infections in children, the elderly, and immunocompromised patients. The fusion (F) protein is the major target of neutralizing antibodies. Recent developments in stabilizing the pre-fusion conformation of the F proteins, and identifying immunodominant epitopes that elicit potent neutralizing antibodies have led to the testing of numerous pre-fusion RSV F-based vaccines in clinical trials. We designed and tested the immunogenicity and protective efficacy of a chimeric fusion protein that contains immunodominant epitopes of RSV F and hMPV F (RHMS-1). RHMS-1 has several advantages over vaccination with pre-fusion RSV F or hMPV F, including a focus on recalling B cells to the most important protective epitopes and the ability to induce protection against two viruses with a single antigen. RHMS-1 was generated as a trimeric recombinant protein, and analysis by negative-stain electron microscopy demonstrated the protein resembles the pre-fusion conformation. Probing of RHMS-1 antigenicity using a panel of RSV and hMPV F-specific monoclonal antibodies (mAbs) revealed the protein retains features of both viruses, including the pre-fusion site Ø epitope of RSV F. Mice immunized with RHMS-1 generated neutralizing antibodies to both viruses and were completely protected from RSV or hMPV challenge. Overall, this study demonstrates protection against two viruses with a single antigen and supports testing of RHMS-1 in additional pre-clinical animal models. |
| first_indexed | 2024-12-10T17:14:17Z |
| format | Article |
| id | doaj.art-c1774d02e4394f92ba04e2b0d549a41f |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-10T17:14:17Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-c1774d02e4394f92ba04e2b0d549a41f2022-12-22T01:40:11ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-08-011310.3389/fimmu.2022.941865941865A Pan-Pneumovirus vaccine based on immunodominant epitopes of the fusion proteinJiachen Huang0Jiachen Huang1Rose J. Miller2Rose J. Miller3Jarrod J. Mousa4Jarrod J. Mousa5Jarrod J. Mousa6Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA, United StatesCenter for Vaccines and Immunology, College of Veterinary Medicine, University of Georgia, Athens, GA, United StatesDepartment of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA, United StatesCenter for Vaccines and Immunology, College of Veterinary Medicine, University of Georgia, Athens, GA, United StatesDepartment of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA, United StatesCenter for Vaccines and Immunology, College of Veterinary Medicine, University of Georgia, Athens, GA, United StatesDepartment of Biochemistry and Molecular Biology, Franklin College of Arts and Sciences, University of Georgia, Athens, GA, United StatesRespiratory syncytial virus (RSV) and human metapneumovirus (hMPV) are two leading causes of severe respiratory infections in children, the elderly, and immunocompromised patients. The fusion (F) protein is the major target of neutralizing antibodies. Recent developments in stabilizing the pre-fusion conformation of the F proteins, and identifying immunodominant epitopes that elicit potent neutralizing antibodies have led to the testing of numerous pre-fusion RSV F-based vaccines in clinical trials. We designed and tested the immunogenicity and protective efficacy of a chimeric fusion protein that contains immunodominant epitopes of RSV F and hMPV F (RHMS-1). RHMS-1 has several advantages over vaccination with pre-fusion RSV F or hMPV F, including a focus on recalling B cells to the most important protective epitopes and the ability to induce protection against two viruses with a single antigen. RHMS-1 was generated as a trimeric recombinant protein, and analysis by negative-stain electron microscopy demonstrated the protein resembles the pre-fusion conformation. Probing of RHMS-1 antigenicity using a panel of RSV and hMPV F-specific monoclonal antibodies (mAbs) revealed the protein retains features of both viruses, including the pre-fusion site Ø epitope of RSV F. Mice immunized with RHMS-1 generated neutralizing antibodies to both viruses and were completely protected from RSV or hMPV challenge. Overall, this study demonstrates protection against two viruses with a single antigen and supports testing of RHMS-1 in additional pre-clinical animal models.https://www.frontiersin.org/articles/10.3389/fimmu.2022.941865/fullRSV (respiratory syncytial virus)human metapneumovirus (hMPV)vaccinestructure-based vaccine designneutralizing antibodiesfusion protein |
| spellingShingle | Jiachen Huang Jiachen Huang Rose J. Miller Rose J. Miller Jarrod J. Mousa Jarrod J. Mousa Jarrod J. Mousa A Pan-Pneumovirus vaccine based on immunodominant epitopes of the fusion protein Frontiers in Immunology RSV (respiratory syncytial virus) human metapneumovirus (hMPV) vaccine structure-based vaccine design neutralizing antibodies fusion protein |
| title | A Pan-Pneumovirus vaccine based on immunodominant epitopes of the fusion protein |
| title_full | A Pan-Pneumovirus vaccine based on immunodominant epitopes of the fusion protein |
| title_fullStr | A Pan-Pneumovirus vaccine based on immunodominant epitopes of the fusion protein |
| title_full_unstemmed | A Pan-Pneumovirus vaccine based on immunodominant epitopes of the fusion protein |
| title_short | A Pan-Pneumovirus vaccine based on immunodominant epitopes of the fusion protein |
| title_sort | pan pneumovirus vaccine based on immunodominant epitopes of the fusion protein |
| topic | RSV (respiratory syncytial virus) human metapneumovirus (hMPV) vaccine structure-based vaccine design neutralizing antibodies fusion protein |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.941865/full |
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