Cell-Based Influenza A/H1N1pdm09 Vaccine Viruses Containing Chimeric Hemagglutinin with Improved Membrane Fusion Ability
The H1N1 influenza pandemic vaccine has been developed from the A/California/07/09 (Cal) virus and the well-known high-yield A/Puerto Rico/8/34 (PR8) virus by classical reassortment and reverse genetics (RG) in eggs. Previous studies have suggested that Cal-derived chimeric hemagglutinin (HA) and ne...
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MDPI AG
2020-08-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/8/3/458 |
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| author | Madoka Kawahara Toshiya Wada Fumitaka Momose Eri Nobusawa Yuko Morikawa |
| author_facet | Madoka Kawahara Toshiya Wada Fumitaka Momose Eri Nobusawa Yuko Morikawa |
| author_sort | Madoka Kawahara |
| collection | DOAJ |
| description | The H1N1 influenza pandemic vaccine has been developed from the A/California/07/09 (Cal) virus and the well-known high-yield A/Puerto Rico/8/34 (PR8) virus by classical reassortment and reverse genetics (RG) in eggs. Previous studies have suggested that Cal-derived chimeric hemagglutinin (HA) and neuraminidase (NA) improve virus yields. However, the cell-based vaccine of the H1N1 pandemic virus has been less investigated. RG viruses that contained Cal-derived chimeric HA and NA could be rescued in Madin–Darby canine kidney cells that expressed α2,6-sialyltransferase (MDCK-SIAT1). The viral growth kinetics and chimeric HA and NA properties were analyzed. We attempted to generate various RG viruses that contained Cal-derived chimeric HA and NA, but half of them could not be rescued in MDCK-SIAT1 cells. When both the 3′- and 5′-terminal regions of Cal HA viral RNA were replaced with the corresponding regions of PR8 HA, the RG viruses were rescued. Our results were largely consistent with those of previous studies, in which the N- and C-terminal chimeric HA slightly improved virus yield. Importantly, the chimeric HA, compared to Cal HA, showed cell fusion ability at a broader pH range, likely due to amino acid substitutions in the transmembrane region of HA. The rescued RG virus with high virus yield harbored the chimeric HA capable of cell fusion at a broader range of pH. |
| first_indexed | 2024-03-10T17:10:42Z |
| format | Article |
| id | doaj.art-05187dae423a42a2937b07006a79f62d |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-10T17:10:42Z |
| publishDate | 2020-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-05187dae423a42a2937b07006a79f62d2023-11-20T10:39:38ZengMDPI AGVaccines2076-393X2020-08-018345810.3390/vaccines8030458Cell-Based Influenza A/H1N1pdm09 Vaccine Viruses Containing Chimeric Hemagglutinin with Improved Membrane Fusion AbilityMadoka Kawahara0Toshiya Wada1Fumitaka Momose2Eri Nobusawa3Yuko Morikawa4Kitasato Institute for Life Sciences, Kitasato University, Tokyo 108-8641, JapanKitasato Institute for Life Sciences, Kitasato University, Tokyo 108-8641, JapanKitasato Institute for Life Sciences, Kitasato University, Tokyo 108-8641, JapanInfluenza Virus Research Center, National Institute of Infectious Diseases, Tokyo 208-0011, JapanKitasato Institute for Life Sciences, Kitasato University, Tokyo 108-8641, JapanThe H1N1 influenza pandemic vaccine has been developed from the A/California/07/09 (Cal) virus and the well-known high-yield A/Puerto Rico/8/34 (PR8) virus by classical reassortment and reverse genetics (RG) in eggs. Previous studies have suggested that Cal-derived chimeric hemagglutinin (HA) and neuraminidase (NA) improve virus yields. However, the cell-based vaccine of the H1N1 pandemic virus has been less investigated. RG viruses that contained Cal-derived chimeric HA and NA could be rescued in Madin–Darby canine kidney cells that expressed α2,6-sialyltransferase (MDCK-SIAT1). The viral growth kinetics and chimeric HA and NA properties were analyzed. We attempted to generate various RG viruses that contained Cal-derived chimeric HA and NA, but half of them could not be rescued in MDCK-SIAT1 cells. When both the 3′- and 5′-terminal regions of Cal HA viral RNA were replaced with the corresponding regions of PR8 HA, the RG viruses were rescued. Our results were largely consistent with those of previous studies, in which the N- and C-terminal chimeric HA slightly improved virus yield. Importantly, the chimeric HA, compared to Cal HA, showed cell fusion ability at a broader pH range, likely due to amino acid substitutions in the transmembrane region of HA. The rescued RG virus with high virus yield harbored the chimeric HA capable of cell fusion at a broader range of pH.https://www.mdpi.com/2076-393X/8/3/458influenzaH1N1 2009cell-based vaccinereverse geneticschimericPR8 |
| spellingShingle | Madoka Kawahara Toshiya Wada Fumitaka Momose Eri Nobusawa Yuko Morikawa Cell-Based Influenza A/H1N1pdm09 Vaccine Viruses Containing Chimeric Hemagglutinin with Improved Membrane Fusion Ability Vaccines influenza H1N1 2009 cell-based vaccine reverse genetics chimeric PR8 |
| title | Cell-Based Influenza A/H1N1pdm09 Vaccine Viruses Containing Chimeric Hemagglutinin with Improved Membrane Fusion Ability |
| title_full | Cell-Based Influenza A/H1N1pdm09 Vaccine Viruses Containing Chimeric Hemagglutinin with Improved Membrane Fusion Ability |
| title_fullStr | Cell-Based Influenza A/H1N1pdm09 Vaccine Viruses Containing Chimeric Hemagglutinin with Improved Membrane Fusion Ability |
| title_full_unstemmed | Cell-Based Influenza A/H1N1pdm09 Vaccine Viruses Containing Chimeric Hemagglutinin with Improved Membrane Fusion Ability |
| title_short | Cell-Based Influenza A/H1N1pdm09 Vaccine Viruses Containing Chimeric Hemagglutinin with Improved Membrane Fusion Ability |
| title_sort | cell based influenza a h1n1pdm09 vaccine viruses containing chimeric hemagglutinin with improved membrane fusion ability |
| topic | influenza H1N1 2009 cell-based vaccine reverse genetics chimeric PR8 |
| url | https://www.mdpi.com/2076-393X/8/3/458 |
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