A universal SARS‐CoV DNA vaccine inducing highly cross‐reactive neutralizing antibodies and T cells
Abstract New variants in the SARS‐CoV‐2 pandemic are more contagious (Alpha/Delta), evade neutralizing antibodies (Beta), or both (Omicron). This poses a challenge in vaccine development according to WHO. We designed a more universal SARS‐CoV‐2 DNA vaccine containing receptor‐binding domain loops fr...
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| Format: | Article |
| Language: | English |
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Springer Nature
2022-09-01
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| Series: | EMBO Molecular Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.15252/emmm.202215821 |
| _version_ | 1827045105924571136 |
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| author | Sofia Appelberg Gustaf Ahlén Jingyi Yan Negin Nikouyan Sofie Weber Olivia Larsson Urban Höglund Soo Aleman Friedemann Weber Emma Perlhamre Johanna Apro Eva‐Karin Gidlund Ola Tuvesson Simona Salati Matteo Cadossi Hanna Tegel Sophia Hober Lars Frelin Ali Mirazimi Matti Sällberg |
| author_facet | Sofia Appelberg Gustaf Ahlén Jingyi Yan Negin Nikouyan Sofie Weber Olivia Larsson Urban Höglund Soo Aleman Friedemann Weber Emma Perlhamre Johanna Apro Eva‐Karin Gidlund Ola Tuvesson Simona Salati Matteo Cadossi Hanna Tegel Sophia Hober Lars Frelin Ali Mirazimi Matti Sällberg |
| author_sort | Sofia Appelberg |
| collection | DOAJ |
| description | Abstract New variants in the SARS‐CoV‐2 pandemic are more contagious (Alpha/Delta), evade neutralizing antibodies (Beta), or both (Omicron). This poses a challenge in vaccine development according to WHO. We designed a more universal SARS‐CoV‐2 DNA vaccine containing receptor‐binding domain loops from the huCoV‐19/WH01, the Alpha, and the Beta variants, combined with the membrane and nucleoproteins. The vaccine induced spike antibodies crossreactive between huCoV‐19/WH01, Beta, and Delta spike proteins that neutralized huCoV‐19/WH01, Beta, Delta, and Omicron virus in vitro. The vaccine primed nucleoprotein‐specific T cells, unlike spike‐specific T cells, recognized Bat‐CoV sequences. The vaccine protected mice carrying the human ACE2 receptor against lethal infection with the SARS‐CoV‐2 Beta variant. Interestingly, priming of cross‐reactive nucleoprotein‐specific T cells alone was 60% protective, verifying observations from humans that T cells protect against lethal disease. This SARS‐CoV vaccine induces a uniquely broad and functional immunity that adds to currently used vaccines. |
| first_indexed | 2024-03-07T18:30:49Z |
| format | Article |
| id | doaj.art-35ec9af66e3647f5894151746b9c3202 |
| institution | Directory Open Access Journal |
| issn | 1757-4676 1757-4684 |
| language | English |
| last_indexed | 2025-02-18T14:19:35Z |
| publishDate | 2022-09-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj.art-35ec9af66e3647f5894151746b9c32022024-10-28T08:51:39ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842022-09-01141011110.15252/emmm.202215821A universal SARS‐CoV DNA vaccine inducing highly cross‐reactive neutralizing antibodies and T cellsSofia Appelberg0Gustaf Ahlén1Jingyi Yan2Negin Nikouyan3Sofie Weber4Olivia Larsson5Urban Höglund6Soo Aleman7Friedemann Weber8Emma Perlhamre9Johanna Apro10Eva‐Karin Gidlund11Ola Tuvesson12Simona Salati13Matteo Cadossi14Hanna Tegel15Sophia Hober16Lars Frelin17Ali Mirazimi18Matti Sällberg19Public Health Agency of SwedenDepartment of Laboratory Medicine, Karolinska InstitutetDepartment of Laboratory Medicine, Karolinska InstitutetDepartment of Laboratory Medicine, Karolinska InstitutetAdlego ABAdlego ABAdlego ABDepartment of Infectious Disease, Karolinska University HospitalInstitute for Virology, FB10‐Veterinary Medicine, Justus‐Liebing University GiessenKarolinska Trial Alliance, Karolinska University HospitalKarolinska Trial Alliance, Karolinska University HospitalNorthX BiologicsNorthX BiologicsIGEA Bomedical SpaIGEA Bomedical SpaDepartment of Protein Science, Royal Institute of TechnologyDepartment of Protein Science, Royal Institute of TechnologyDepartment of Laboratory Medicine, Karolinska InstitutetPublic Health Agency of SwedenDepartment of Laboratory Medicine, Karolinska InstitutetAbstract New variants in the SARS‐CoV‐2 pandemic are more contagious (Alpha/Delta), evade neutralizing antibodies (Beta), or both (Omicron). This poses a challenge in vaccine development according to WHO. We designed a more universal SARS‐CoV‐2 DNA vaccine containing receptor‐binding domain loops from the huCoV‐19/WH01, the Alpha, and the Beta variants, combined with the membrane and nucleoproteins. The vaccine induced spike antibodies crossreactive between huCoV‐19/WH01, Beta, and Delta spike proteins that neutralized huCoV‐19/WH01, Beta, Delta, and Omicron virus in vitro. The vaccine primed nucleoprotein‐specific T cells, unlike spike‐specific T cells, recognized Bat‐CoV sequences. The vaccine protected mice carrying the human ACE2 receptor against lethal infection with the SARS‐CoV‐2 Beta variant. Interestingly, priming of cross‐reactive nucleoprotein‐specific T cells alone was 60% protective, verifying observations from humans that T cells protect against lethal disease. This SARS‐CoV vaccine induces a uniquely broad and functional immunity that adds to currently used vaccines.https://doi.org/10.15252/emmm.202215821DNA vaccinein vivo electroporationpreclinical developmentSARS‐CoV‐2universal SARS vaccine |
| spellingShingle | Sofia Appelberg Gustaf Ahlén Jingyi Yan Negin Nikouyan Sofie Weber Olivia Larsson Urban Höglund Soo Aleman Friedemann Weber Emma Perlhamre Johanna Apro Eva‐Karin Gidlund Ola Tuvesson Simona Salati Matteo Cadossi Hanna Tegel Sophia Hober Lars Frelin Ali Mirazimi Matti Sällberg A universal SARS‐CoV DNA vaccine inducing highly cross‐reactive neutralizing antibodies and T cells EMBO Molecular Medicine DNA vaccine in vivo electroporation preclinical development SARS‐CoV‐2 universal SARS vaccine |
| title | A universal SARS‐CoV DNA vaccine inducing highly cross‐reactive neutralizing antibodies and T cells |
| title_full | A universal SARS‐CoV DNA vaccine inducing highly cross‐reactive neutralizing antibodies and T cells |
| title_fullStr | A universal SARS‐CoV DNA vaccine inducing highly cross‐reactive neutralizing antibodies and T cells |
| title_full_unstemmed | A universal SARS‐CoV DNA vaccine inducing highly cross‐reactive neutralizing antibodies and T cells |
| title_short | A universal SARS‐CoV DNA vaccine inducing highly cross‐reactive neutralizing antibodies and T cells |
| title_sort | universal sars cov dna vaccine inducing highly cross reactive neutralizing antibodies and t cells |
| topic | DNA vaccine in vivo electroporation preclinical development SARS‐CoV‐2 universal SARS vaccine |
| url | https://doi.org/10.15252/emmm.202215821 |
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