دورية أكاديمية
Safety, Immunogenicity, and Protective Efficacy of a Chimeric A/B Live Attenuated Influenza Vaccine in a Mouse Model
| العنوان: | Safety, Immunogenicity, and Protective Efficacy of a Chimeric A/B Live Attenuated Influenza Vaccine in a Mouse Model |
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| المؤلفون: | Ekaterina Stepanova, Elena Krutikova, Pei-Fong Wong, Victoria Matyushenko, Ekaterina Bazhenova, Irina Isakova-Sivak, Larisa Rudenko |
| المصدر: | Microorganisms, Vol 9, Iss 2, p 259 (2021) |
| بيانات النشر: | MDPI AG, 2021. |
| سنة النشر: | 2021 |
| المجموعة: | LCC:Biology (General) |
| مصطلحات موضوعية: | live attenuated influenza vaccine, LAIV, influenza virus, genome packaging, reassortment, influenza B virus, Biology (General), QH301-705.5 |
| الوصف: | Influenza A and B viruses cause significant morbidity and mortality worldwide. Current influenza vaccines are composed of three or four strains: A/H1N1, A/H3N2, and B (Victoria and Yamagata lineages). It is of great interest if immunization against both type A and B influenza viruses can be combined in a single vaccine strain, thus reducing the cost of vaccine production and the possibility of strain interference within the multicomponent vaccine. In the current study, we developed an experimental live cold-adapted influenza intertype reassortant (influenza A and B) vaccine on the live attenuated influenza vaccine (LAIV) A/Leningrad/134/17/57 backbone. Hemagglutinin (HA) and neuraminidase (NA) functional domains were inherited from the influenza B/Brisbane/60/2008 strain, whereas their packaging signals were substituted with appropriate fragments of influenza A virus genes. The recombinant A/B virus efficiently replicated in eggs and Madin–Darby Canine Kidney (MDCK) cells under optimal conditions, temperature-sensitive phenotype was maintained, and its antigenic properties matched the influenza B parental virus. The chimeric vaccine was attenuated in mice: after intranasal immunization, viral replication was seen only in nasal turbinates but not in the lungs. Immunological studies demonstrated the induction of IgG antibody responses against the influenza A and B virus, whereas hemagglutination inhibition (HAI) and neutralizing antibodies were detected only against the influenza B virus, resulting in significant protection of immunized animals against influenza B virus challenge. IFNγ-secreting CD8 effector memory T cells (CD44+CD62L−) were detected in mouse splenocytes after stimulation with the specific influenza A peptide (NP366); however, the T-cell response was not sufficient to protect animals against infection with a high-dose mouse-adapted A/California/07/2009 (H1N1pdm09) virus, most probably due to the mismatch of key T-cell epitopes of the H1N1 virus and the LAIV backbone. Overall, generation of the chimeric A/B LAIV virus on a licensed LAIV backbone demonstrated prospects for the development of safe and efficacious vaccine candidates that afford combined protection against both type A and type B influenza viruses; however, further optimization of the T-cell epitope content within the LAIV backbone may be required. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2076-2607 07122802 |
| Relation: | https://www.mdpi.com/2076-2607/9/2/259; https://doaj.org/toc/2076-2607 |
| DOI: | 10.3390/microorganisms9020259 |
| URL الوصول: | https://doaj.org/article/e071228022c947f4b272fc3062fe9ac9 |
| رقم الأكسشن: | edsdoj.071228022c947f4b272fc3062fe9ac9 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 20762607 07122802 |
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| DOI: | 10.3390/microorganisms9020259 |