Development of a respiratory syncytial virus vaccine using human hepatitis B core-based virus-like particles to induce mucosal immunity
Copyright © 2021 Elsevier Ltd. All rights reserved..
BACKGROUND: Respiratory syncytial virus (RSV) is an important viral pathogen responsible for severe infection of the lower respiratory tract in children under the age of 5 years. No vaccines against RSV are currently in clinical use. Vaccine-associated enhanced respiratory disease (ERD) caused by excess Th2 type responses was observed in a clinical trial of formalin-inactivated RSV (FI-RSV) in antigen-naïve infants. Thus, inducing a balanced immune response is a crucial issue in the development of an RSV vaccine.
METHODS: In this study, we constructed, expressed, and purified a recombinant RSV vaccine candidate (i.e., HRØ24) containing the two heptad repeat regions and the antigenic sites Ø, II, and IV of the RSV F protein. The RSV vaccine candidate was intranasally administrated to BALB/c and C57BL/6 mice in combination with virus-like particles (VLPs) derived from the core protein of the hepatitis B virus (HBc). Mucosal immunity to HRØ24 was then assessed.
RESULTS: Intranasal administration of HBc VLPs in combination with HRØ24 induced serum IgGs against HRØ24 as well as lung HRØ24-specific sIgAs in both C57BL/6 and BALB/c mouse models. The secretion of IFN-γ from splenocyte re-stimulation and an elevated ratio of serum IgG2a to IgG1 indicated that the immune response induced by the HBc VLPs/HRØ24 mixture was Th1-biased. Weight loss of <5% and no to low eosinophil infiltration was observed in histological analysis of the lung following a challenge with the RSV A2 strain. These results suggest that the HBc VLPs/HRØ24 combination conferred substantial partial protection against RSV-induced illness in mice.
CONCLUSIONS: Long-term immunity to RSV-induced illness was achieved via intranasal vaccination using a mixture of HBc VLPs and HRØ24 in mouse models.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:39 |
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| Enthalten in: |
Vaccine - 39(2021), 24 vom: 02. Juni, Seite 3259-3269 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Huang, Jen-Min [VerfasserIn] |
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| Links: |
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| Themen: |
Adjuvant |
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| Anmerkungen: |
Date Completed 08.07.2021 Date Revised 08.07.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.vaccine.2021.04.038 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Copyright © 2021 Elsevier Ltd. All rights reserved. | ||
| 520 | |a BACKGROUND: Respiratory syncytial virus (RSV) is an important viral pathogen responsible for severe infection of the lower respiratory tract in children under the age of 5 years. No vaccines against RSV are currently in clinical use. Vaccine-associated enhanced respiratory disease (ERD) caused by excess Th2 type responses was observed in a clinical trial of formalin-inactivated RSV (FI-RSV) in antigen-naïve infants. Thus, inducing a balanced immune response is a crucial issue in the development of an RSV vaccine | ||
| 520 | |a METHODS: In this study, we constructed, expressed, and purified a recombinant RSV vaccine candidate (i.e., HRØ24) containing the two heptad repeat regions and the antigenic sites Ø, II, and IV of the RSV F protein. The RSV vaccine candidate was intranasally administrated to BALB/c and C57BL/6 mice in combination with virus-like particles (VLPs) derived from the core protein of the hepatitis B virus (HBc). Mucosal immunity to HRØ24 was then assessed | ||
| 520 | |a RESULTS: Intranasal administration of HBc VLPs in combination with HRØ24 induced serum IgGs against HRØ24 as well as lung HRØ24-specific sIgAs in both C57BL/6 and BALB/c mouse models. The secretion of IFN-γ from splenocyte re-stimulation and an elevated ratio of serum IgG2a to IgG1 indicated that the immune response induced by the HBc VLPs/HRØ24 mixture was Th1-biased. Weight loss of <5% and no to low eosinophil infiltration was observed in histological analysis of the lung following a challenge with the RSV A2 strain. These results suggest that the HBc VLPs/HRØ24 combination conferred substantial partial protection against RSV-induced illness in mice | ||
| 520 | |a CONCLUSIONS: Long-term immunity to RSV-induced illness was achieved via intranasal vaccination using a mixture of HBc VLPs and HRØ24 in mouse models | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Tseng, Yu-Kai |e verfasserin |4 aut | |
| 700 | 1 | |a Chi, Ya-Hui |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Li-Min |e verfasserin |4 aut | |
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