Self-assembling SARS-CoV-2 spike-HBsAg nanoparticles elicit potent and durable neutralizing antibody responses via genetic delivery
Abstract While several COVID-19 vaccines have been in use, more effective and durable vaccines are needed to combat the ongoing COVID-19 pandemic. Here, we report highly immunogenic self-assembling SARS-CoV-2 spike-HBsAg nanoparticles displaying a six-proline-stabilized WA1 (wild type, WT) spike S6P...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-08-01
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| Series: | npj Vaccines |
| Online Access: | https://doi.org/10.1038/s41541-023-00707-w |
| _version_ | 1797578336303579136 |
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| author | Cuiping Liu Lingshu Wang Jonah S. Merriam Wei Shi Eun Sung Yang Yi Zhang Man Chen Wing-Pui Kong Cheng Cheng Yaroslav Tsybovsky Tyler Stephens Raffaello Verardi Kwanyee Leung Cody Stein Adam S. Olia Darcy R. Harris Misook Choe Baoshan Zhang Barney S. Graham Peter D. Kwong Richard A. Koup Amarendra Pegu John R. Mascola |
| author_facet | Cuiping Liu Lingshu Wang Jonah S. Merriam Wei Shi Eun Sung Yang Yi Zhang Man Chen Wing-Pui Kong Cheng Cheng Yaroslav Tsybovsky Tyler Stephens Raffaello Verardi Kwanyee Leung Cody Stein Adam S. Olia Darcy R. Harris Misook Choe Baoshan Zhang Barney S. Graham Peter D. Kwong Richard A. Koup Amarendra Pegu John R. Mascola |
| author_sort | Cuiping Liu |
| collection | DOAJ |
| description | Abstract While several COVID-19 vaccines have been in use, more effective and durable vaccines are needed to combat the ongoing COVID-19 pandemic. Here, we report highly immunogenic self-assembling SARS-CoV-2 spike-HBsAg nanoparticles displaying a six-proline-stabilized WA1 (wild type, WT) spike S6P on a HBsAg core. These S6P-HBsAgs bound diverse domain-specific SARS-CoV-2 monoclonal antibodies. In mice with and without a HBV pre-vaccination, DNA immunization with S6P-HBsAgs elicited significantly more potent and durable neutralizing antibody (nAb) responses against diverse SARS-CoV-2 strains than that of soluble S2P or S6P, or full-length S2P with its coding sequence matching mRNA-1273. The nAb responses elicited by S6P-HBsAgs persisted substantially longer than by soluble S2P or S6P and appeared to be enhanced by HBsAg pre-exposure. These data show that genetic delivery of SARS-CoV-2 S6P-HBsAg nanoparticles can elicit greater and more durable nAb responses than non-nanoparticle forms of stabilized spike. Our findings highlight the potential of S6P-HBsAgs as next generation genetic vaccine candidates against SARS-CoV-2. |
| first_indexed | 2024-03-10T22:20:31Z |
| format | Article |
| id | doaj.art-9b37253d44914adeb9ec845f4062bcd4 |
| institution | Directory Open Access Journal |
| issn | 2059-0105 |
| language | English |
| last_indexed | 2024-03-10T22:20:31Z |
| publishDate | 2023-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Vaccines |
| spelling | doaj.art-9b37253d44914adeb9ec845f4062bcd42023-11-19T12:18:02ZengNature Portfolionpj Vaccines2059-01052023-08-018111010.1038/s41541-023-00707-wSelf-assembling SARS-CoV-2 spike-HBsAg nanoparticles elicit potent and durable neutralizing antibody responses via genetic deliveryCuiping Liu0Lingshu Wang1Jonah S. Merriam2Wei Shi3Eun Sung Yang4Yi Zhang5Man Chen6Wing-Pui Kong7Cheng Cheng8Yaroslav Tsybovsky9Tyler Stephens10Raffaello Verardi11Kwanyee Leung12Cody Stein13Adam S. Olia14Darcy R. Harris15Misook Choe16Baoshan Zhang17Barney S. Graham18Peter D. Kwong19Richard A. Koup20Amarendra Pegu21John R. Mascola22Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIHVaccine Research Center, National Institute of Allergy and Infectious Diseases, NIHVaccine Research Center, National Institute of Allergy and Infectious Diseases, NIHVaccine Research Center, National Institute of Allergy and Infectious Diseases, NIHVaccine Research Center, National Institute of Allergy and Infectious Diseases, NIHVaccine Research Center, National Institute of Allergy and Infectious Diseases, NIHVaccine Research Center, National Institute of Allergy and Infectious Diseases, NIHVaccine Research Center, National Institute of Allergy and Infectious Diseases, NIHVaccine Research Center, National Institute of Allergy and Infectious Diseases, NIHVaccine Research Center Electron Microscopy Unit, Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer ResearchVaccine Research Center Electron Microscopy Unit, Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer ResearchVaccine Research Center, National Institute of Allergy and Infectious Diseases, NIHVaccine Research Center, National Institute of Allergy and Infectious Diseases, NIHVaccine Research Center, National Institute of Allergy and Infectious Diseases, NIHVaccine Research Center, National Institute of Allergy and Infectious Diseases, NIHVaccine Research Center, National Institute of Allergy and Infectious Diseases, NIHVaccine Research Center, National Institute of Allergy and Infectious Diseases, NIHVaccine Research Center, National Institute of Allergy and Infectious Diseases, NIHVaccine Research Center, National Institute of Allergy and Infectious Diseases, NIHVaccine Research Center, National Institute of Allergy and Infectious Diseases, NIHVaccine Research Center, National Institute of Allergy and Infectious Diseases, NIHVaccine Research Center, National Institute of Allergy and Infectious Diseases, NIHVaccine Research Center, National Institute of Allergy and Infectious Diseases, NIHAbstract While several COVID-19 vaccines have been in use, more effective and durable vaccines are needed to combat the ongoing COVID-19 pandemic. Here, we report highly immunogenic self-assembling SARS-CoV-2 spike-HBsAg nanoparticles displaying a six-proline-stabilized WA1 (wild type, WT) spike S6P on a HBsAg core. These S6P-HBsAgs bound diverse domain-specific SARS-CoV-2 monoclonal antibodies. In mice with and without a HBV pre-vaccination, DNA immunization with S6P-HBsAgs elicited significantly more potent and durable neutralizing antibody (nAb) responses against diverse SARS-CoV-2 strains than that of soluble S2P or S6P, or full-length S2P with its coding sequence matching mRNA-1273. The nAb responses elicited by S6P-HBsAgs persisted substantially longer than by soluble S2P or S6P and appeared to be enhanced by HBsAg pre-exposure. These data show that genetic delivery of SARS-CoV-2 S6P-HBsAg nanoparticles can elicit greater and more durable nAb responses than non-nanoparticle forms of stabilized spike. Our findings highlight the potential of S6P-HBsAgs as next generation genetic vaccine candidates against SARS-CoV-2.https://doi.org/10.1038/s41541-023-00707-w |
| spellingShingle | Cuiping Liu Lingshu Wang Jonah S. Merriam Wei Shi Eun Sung Yang Yi Zhang Man Chen Wing-Pui Kong Cheng Cheng Yaroslav Tsybovsky Tyler Stephens Raffaello Verardi Kwanyee Leung Cody Stein Adam S. Olia Darcy R. Harris Misook Choe Baoshan Zhang Barney S. Graham Peter D. Kwong Richard A. Koup Amarendra Pegu John R. Mascola Self-assembling SARS-CoV-2 spike-HBsAg nanoparticles elicit potent and durable neutralizing antibody responses via genetic delivery npj Vaccines |
| title | Self-assembling SARS-CoV-2 spike-HBsAg nanoparticles elicit potent and durable neutralizing antibody responses via genetic delivery |
| title_full | Self-assembling SARS-CoV-2 spike-HBsAg nanoparticles elicit potent and durable neutralizing antibody responses via genetic delivery |
| title_fullStr | Self-assembling SARS-CoV-2 spike-HBsAg nanoparticles elicit potent and durable neutralizing antibody responses via genetic delivery |
| title_full_unstemmed | Self-assembling SARS-CoV-2 spike-HBsAg nanoparticles elicit potent and durable neutralizing antibody responses via genetic delivery |
| title_short | Self-assembling SARS-CoV-2 spike-HBsAg nanoparticles elicit potent and durable neutralizing antibody responses via genetic delivery |
| title_sort | self assembling sars cov 2 spike hbsag nanoparticles elicit potent and durable neutralizing antibody responses via genetic delivery |
| url | https://doi.org/10.1038/s41541-023-00707-w |
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