Virus-Like Particles Assembled Using Respiratory Syncytial Virus Matrix Protein Elicit Protective Immunity in Mice
Su-Hwa Lee,1,* Ki-Back Chu,2,* Min-Ju Kim,3 Fu-Shi Quan1,2 1Department of Medical Zoology, School of Medicine, Kyung Hee University, Seoul, Republic of Korea; 2Medical Research Center for Bioreaction to Reactive Oxygen Species and Biomedical Science Institute, Core Research Institute...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2023-09-01
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| Series: | Infection and Drug Resistance |
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| Online Access: | https://www.dovepress.com/virus-like-particles-assembled-using-respiratory-syncytial-virus-matri-peer-reviewed-fulltext-article-IDR |
| _version_ | 1797685495946280960 |
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| author | Lee SH Chu KB Kim MJ Quan FS |
| author_facet | Lee SH Chu KB Kim MJ Quan FS |
| author_sort | Lee SH |
| collection | DOAJ |
| description | Su-Hwa Lee,1,* Ki-Back Chu,2,* Min-Ju Kim,3 Fu-Shi Quan1,2 1Department of Medical Zoology, School of Medicine, Kyung Hee University, Seoul, Republic of Korea; 2Medical Research Center for Bioreaction to Reactive Oxygen Species and Biomedical Science Institute, Core Research Institute, School of Medicine, Kyung Hee University, Seoul, Republic of Korea; 3Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul, Republic of Korea*These authors contributed equally to this workCorrespondence: Fu-Shi Quan, Department of Medical Zoology, School of Medicine, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447, Republic of Korea, Tel/Fax +82-2-961-2302, Email fsquan@khu.ac.krPurpose: Heterologous virus-like particle (VLP) assembly involving influenza or the Newcastle disease virus matrix protein (M) has been extensively used to explore the efficacies of VLP vaccines against the respiratory syncytial virus (RSV). Here, we attempted to generate homologous RSV VLPs by expressing the pre-fusion (pre-F) or the glycoprotein (G) on the RSV M protein and evaluated their protective efficacy in mice.Methods: We generated VLPs using the baculovirus expression system in Spodoptera frugiperda (Sf9) insect cells. Recombinant baculoviruses expressing the RSV pre-F, G, and M antigens were inoculated into Sf9 cells, and particles were self-assembled. Mice were immunized with either pre-F or G-expressing VLPs, and immune parameters were assessed to determine protection.Results: Our findings show that successful VLP assembly can be achieved by utilizing recombinant baculoviruses expressing the RSV pre-F or G proteins with the native matrix protein. Mice immunized with either pre-F or the G antigen-expressing VLPs elicited robust serum-mediated virus neutralization. VLP immunization evoked Th1-biased RSV-specific antibody responses in the sera of mice. Following challenge infection with the RSV A2 strain, immunized mice experienced lesser eosinophil and IL-4 accumulation in the lungs, though a substantial increase in TNF-α secretion was observed from CD4+ T cells. Interestingly, splenic antibody-secreting cell responses were substantially enhanced against RSV F antigen, but not against the RSV G antigen following immunization and challenge infection. Immunizing mice with the VLPs significantly inhibited pulmonary histopathology development, as indicated by the diminished inflammatory immune cell influx and mucin secretion.Conclusion: Combined, these vaccine-induced immune responses contributed to successfully inhibiting the RSV replication in the lungs of mice and demonstrated that RSV VLP assembly using insect cell-derived homologous RSV matrix protein is a feasible approach.Keywords: vaccine, protection, native virus antigen, recombinant baculovirus |
| first_indexed | 2024-03-12T00:44:58Z |
| format | Article |
| id | doaj.art-415a64007fad4a2687597c27994741a3 |
| institution | Directory Open Access Journal |
| issn | 1178-6973 |
| language | English |
| last_indexed | 2024-03-12T00:44:58Z |
| publishDate | 2023-09-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Infection and Drug Resistance |
| spelling | doaj.art-415a64007fad4a2687597c27994741a32023-09-14T19:09:01ZengDove Medical PressInfection and Drug Resistance1178-69732023-09-01Volume 166099611086614Virus-Like Particles Assembled Using Respiratory Syncytial Virus Matrix Protein Elicit Protective Immunity in MiceLee SHChu KBKim MJQuan FSSu-Hwa Lee,1,* Ki-Back Chu,2,* Min-Ju Kim,3 Fu-Shi Quan1,2 1Department of Medical Zoology, School of Medicine, Kyung Hee University, Seoul, Republic of Korea; 2Medical Research Center for Bioreaction to Reactive Oxygen Species and Biomedical Science Institute, Core Research Institute, School of Medicine, Kyung Hee University, Seoul, Republic of Korea; 3Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul, Republic of Korea*These authors contributed equally to this workCorrespondence: Fu-Shi Quan, Department of Medical Zoology, School of Medicine, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447, Republic of Korea, Tel/Fax +82-2-961-2302, Email fsquan@khu.ac.krPurpose: Heterologous virus-like particle (VLP) assembly involving influenza or the Newcastle disease virus matrix protein (M) has been extensively used to explore the efficacies of VLP vaccines against the respiratory syncytial virus (RSV). Here, we attempted to generate homologous RSV VLPs by expressing the pre-fusion (pre-F) or the glycoprotein (G) on the RSV M protein and evaluated their protective efficacy in mice.Methods: We generated VLPs using the baculovirus expression system in Spodoptera frugiperda (Sf9) insect cells. Recombinant baculoviruses expressing the RSV pre-F, G, and M antigens were inoculated into Sf9 cells, and particles were self-assembled. Mice were immunized with either pre-F or G-expressing VLPs, and immune parameters were assessed to determine protection.Results: Our findings show that successful VLP assembly can be achieved by utilizing recombinant baculoviruses expressing the RSV pre-F or G proteins with the native matrix protein. Mice immunized with either pre-F or the G antigen-expressing VLPs elicited robust serum-mediated virus neutralization. VLP immunization evoked Th1-biased RSV-specific antibody responses in the sera of mice. Following challenge infection with the RSV A2 strain, immunized mice experienced lesser eosinophil and IL-4 accumulation in the lungs, though a substantial increase in TNF-α secretion was observed from CD4+ T cells. Interestingly, splenic antibody-secreting cell responses were substantially enhanced against RSV F antigen, but not against the RSV G antigen following immunization and challenge infection. Immunizing mice with the VLPs significantly inhibited pulmonary histopathology development, as indicated by the diminished inflammatory immune cell influx and mucin secretion.Conclusion: Combined, these vaccine-induced immune responses contributed to successfully inhibiting the RSV replication in the lungs of mice and demonstrated that RSV VLP assembly using insect cell-derived homologous RSV matrix protein is a feasible approach.Keywords: vaccine, protection, native virus antigen, recombinant baculovirushttps://www.dovepress.com/virus-like-particles-assembled-using-respiratory-syncytial-virus-matri-peer-reviewed-fulltext-article-IDRvaccineprotectionnative virus antigenrecombinant baculovirus |
| spellingShingle | Lee SH Chu KB Kim MJ Quan FS Virus-Like Particles Assembled Using Respiratory Syncytial Virus Matrix Protein Elicit Protective Immunity in Mice Infection and Drug Resistance vaccine protection native virus antigen recombinant baculovirus |
| title | Virus-Like Particles Assembled Using Respiratory Syncytial Virus Matrix Protein Elicit Protective Immunity in Mice |
| title_full | Virus-Like Particles Assembled Using Respiratory Syncytial Virus Matrix Protein Elicit Protective Immunity in Mice |
| title_fullStr | Virus-Like Particles Assembled Using Respiratory Syncytial Virus Matrix Protein Elicit Protective Immunity in Mice |
| title_full_unstemmed | Virus-Like Particles Assembled Using Respiratory Syncytial Virus Matrix Protein Elicit Protective Immunity in Mice |
| title_short | Virus-Like Particles Assembled Using Respiratory Syncytial Virus Matrix Protein Elicit Protective Immunity in Mice |
| title_sort | virus like particles assembled using respiratory syncytial virus matrix protein elicit protective immunity in mice |
| topic | vaccine protection native virus antigen recombinant baculovirus |
| url | https://www.dovepress.com/virus-like-particles-assembled-using-respiratory-syncytial-virus-matri-peer-reviewed-fulltext-article-IDR |
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