Gamma Irradiation-Inactivated Respiratory Syncytial Virus Vaccine Provides Protection but Exacerbates Pulmonary Inflammation by Switching from Prefusion to Postfusion F Protein
ABSTRACT Respiratory syncytial virus (RSV) is a common respiratory pathogen that causes lower respiratory diseases among infants and elderly people. Moreover, formalin-inactivated RSV (FI-RSV) vaccine induces serious enhanced respiratory disease (ERD). Radiation has been investigated as an alternati...
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2023-08-01
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| Series: | Microbiology Spectrum |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/spectrum.01358-23 |
| _version_ | 1797741743479717888 |
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| author | Fengjia Chen Hae-Ran Park Hyun Jung Ji Yeongkag Kwon Min-Kyu Kim Joon Young Song Ki Bum Ahn Ho Seong Seo |
| author_facet | Fengjia Chen Hae-Ran Park Hyun Jung Ji Yeongkag Kwon Min-Kyu Kim Joon Young Song Ki Bum Ahn Ho Seong Seo |
| author_sort | Fengjia Chen |
| collection | DOAJ |
| description | ABSTRACT Respiratory syncytial virus (RSV) is a common respiratory pathogen that causes lower respiratory diseases among infants and elderly people. Moreover, formalin-inactivated RSV (FI-RSV) vaccine induces serious enhanced respiratory disease (ERD). Radiation has been investigated as an alternative approach for producing inactivated or live-attenuated vaccines, which enhance the antigenicity and heterogeneous protective effects of vaccines compared with conventional formalin inactivation. In this study, we developed an RSV vaccine using gamma irradiation and analyzed its efficacy against RSV vaccine-induced ERD in a mouse model. Although gamma irradiation-inactivated RSV (RI-RSV) carbonylation was lower than FI-RSV carbonylation and RI-RSV showed a significant antibody production and viral clearance, RI-RSV caused more obvious body weight loss, pulmonary eosinophil infiltration, and pulmonary mucus secretion. Further, the conversion of prefusion F (pre-F) to postfusion F (post-F) was significant for both RI-RSV and FI-RSV, while that of RI-RSV was significantly higher than that of FI-RSV. We found that the conversion from pre- to post-F during radiation was caused by radiation-induced reactive oxygen species. Although we could not propose an effective RSV vaccine manufacturing method, we found that ERD was induced by RSV vaccine by various biochemical effects that affect antigen modification during RSV vaccine manufacturing, rather than simply by the combination of formalin and alum. Therefore, these biochemical actions should be considered in future developments of RSV vaccine. IMPORTANCE Radiation inactivation for viral vaccine production has been known to elicit a better immune response than other inactivation methods due to less surface protein damage. However, we found in this study that radiation-inactivated RSV (RI-RSV) vaccine induced a level of immune response similar to that induced by formalin-inactivated RSV (FI-RSV). Although RI-RSV vaccine showed less carbonylation than FI-RSV, it induced more conformational changes from pre-F to post-F due to the gamma radiation-induced reactive oxygen species response, which may be a key factor in RI-RSV-induced ERD. Therefore, ERD induced by RSV vaccine may be due to pre-F to post-F denaturation by random protein modifications caused by external stress. Our findings provide new ideas for inactivated vaccines for RSV and other viruses and confirm the importance of pre-F in RSV vaccines. |
| first_indexed | 2024-03-12T14:31:03Z |
| format | Article |
| id | doaj.art-223cf8179fa94e859bb74c2554ed7ca3 |
| institution | Directory Open Access Journal |
| issn | 2165-0497 |
| language | English |
| last_indexed | 2024-03-12T14:31:03Z |
| publishDate | 2023-08-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | Microbiology Spectrum |
| spelling | doaj.art-223cf8179fa94e859bb74c2554ed7ca32023-08-17T13:04:14ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972023-08-0111410.1128/spectrum.01358-23Gamma Irradiation-Inactivated Respiratory Syncytial Virus Vaccine Provides Protection but Exacerbates Pulmonary Inflammation by Switching from Prefusion to Postfusion F ProteinFengjia Chen0Hae-Ran Park1Hyun Jung Ji2Yeongkag Kwon3Min-Kyu Kim4Joon Young Song5Ki Bum Ahn6Ho Seong Seo7Accelerator Radioisotope Research Section, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup, Republic of KoreaAccelerator Radioisotope Research Section, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup, Republic of KoreaAccelerator Radioisotope Research Section, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup, Republic of KoreaAccelerator Radioisotope Research Section, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup, Republic of KoreaAccelerator Radioisotope Research Section, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup, Republic of KoreaDepartment of Internal Medicine, Korea University College of Medicine, Seoul, Republic of KoreaAccelerator Radioisotope Research Section, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup, Republic of KoreaAccelerator Radioisotope Research Section, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup, Republic of KoreaABSTRACT Respiratory syncytial virus (RSV) is a common respiratory pathogen that causes lower respiratory diseases among infants and elderly people. Moreover, formalin-inactivated RSV (FI-RSV) vaccine induces serious enhanced respiratory disease (ERD). Radiation has been investigated as an alternative approach for producing inactivated or live-attenuated vaccines, which enhance the antigenicity and heterogeneous protective effects of vaccines compared with conventional formalin inactivation. In this study, we developed an RSV vaccine using gamma irradiation and analyzed its efficacy against RSV vaccine-induced ERD in a mouse model. Although gamma irradiation-inactivated RSV (RI-RSV) carbonylation was lower than FI-RSV carbonylation and RI-RSV showed a significant antibody production and viral clearance, RI-RSV caused more obvious body weight loss, pulmonary eosinophil infiltration, and pulmonary mucus secretion. Further, the conversion of prefusion F (pre-F) to postfusion F (post-F) was significant for both RI-RSV and FI-RSV, while that of RI-RSV was significantly higher than that of FI-RSV. We found that the conversion from pre- to post-F during radiation was caused by radiation-induced reactive oxygen species. Although we could not propose an effective RSV vaccine manufacturing method, we found that ERD was induced by RSV vaccine by various biochemical effects that affect antigen modification during RSV vaccine manufacturing, rather than simply by the combination of formalin and alum. Therefore, these biochemical actions should be considered in future developments of RSV vaccine. IMPORTANCE Radiation inactivation for viral vaccine production has been known to elicit a better immune response than other inactivation methods due to less surface protein damage. However, we found in this study that radiation-inactivated RSV (RI-RSV) vaccine induced a level of immune response similar to that induced by formalin-inactivated RSV (FI-RSV). Although RI-RSV vaccine showed less carbonylation than FI-RSV, it induced more conformational changes from pre-F to post-F due to the gamma radiation-induced reactive oxygen species response, which may be a key factor in RI-RSV-induced ERD. Therefore, ERD induced by RSV vaccine may be due to pre-F to post-F denaturation by random protein modifications caused by external stress. Our findings provide new ideas for inactivated vaccines for RSV and other viruses and confirm the importance of pre-F in RSV vaccines.https://journals.asm.org/doi/10.1128/spectrum.01358-23respiratory syncytial virusenhanced respiratory diseaseinactivated vaccinegamma irradiation inactivationprefusion Fpostfusion F |
| spellingShingle | Fengjia Chen Hae-Ran Park Hyun Jung Ji Yeongkag Kwon Min-Kyu Kim Joon Young Song Ki Bum Ahn Ho Seong Seo Gamma Irradiation-Inactivated Respiratory Syncytial Virus Vaccine Provides Protection but Exacerbates Pulmonary Inflammation by Switching from Prefusion to Postfusion F Protein Microbiology Spectrum respiratory syncytial virus enhanced respiratory disease inactivated vaccine gamma irradiation inactivation prefusion F postfusion F |
| title | Gamma Irradiation-Inactivated Respiratory Syncytial Virus Vaccine Provides Protection but Exacerbates Pulmonary Inflammation by Switching from Prefusion to Postfusion F Protein |
| title_full | Gamma Irradiation-Inactivated Respiratory Syncytial Virus Vaccine Provides Protection but Exacerbates Pulmonary Inflammation by Switching from Prefusion to Postfusion F Protein |
| title_fullStr | Gamma Irradiation-Inactivated Respiratory Syncytial Virus Vaccine Provides Protection but Exacerbates Pulmonary Inflammation by Switching from Prefusion to Postfusion F Protein |
| title_full_unstemmed | Gamma Irradiation-Inactivated Respiratory Syncytial Virus Vaccine Provides Protection but Exacerbates Pulmonary Inflammation by Switching from Prefusion to Postfusion F Protein |
| title_short | Gamma Irradiation-Inactivated Respiratory Syncytial Virus Vaccine Provides Protection but Exacerbates Pulmonary Inflammation by Switching from Prefusion to Postfusion F Protein |
| title_sort | gamma irradiation inactivated respiratory syncytial virus vaccine provides protection but exacerbates pulmonary inflammation by switching from prefusion to postfusion f protein |
| topic | respiratory syncytial virus enhanced respiratory disease inactivated vaccine gamma irradiation inactivation prefusion F postfusion F |
| url | https://journals.asm.org/doi/10.1128/spectrum.01358-23 |
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