Attenuated Influenza Virions Expressing the SARS-CoV-2 Receptor-Binding Domain Induce Neutralizing Antibodies in Mice
An effective vaccine is essential for controlling the spread of the SARS-CoV-2 virus. Here, we describe an influenza virus-based vaccine for SARS-CoV-2. We incorporated a membrane-anchored form of the SARS-CoV-2 spike receptor binding domain (RBD) in place of the neuraminidase (NA) coding sequence i...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-09-01
|
| Series: | Viruses |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4915/12/9/987 |
| _version_ | 1797554504950874112 |
|---|---|
| author | Andrea N. Loes Lauren E. Gentles Allison J. Greaney Katharine H. D. Crawford Jesse D. Bloom |
| author_facet | Andrea N. Loes Lauren E. Gentles Allison J. Greaney Katharine H. D. Crawford Jesse D. Bloom |
| author_sort | Andrea N. Loes |
| collection | DOAJ |
| description | An effective vaccine is essential for controlling the spread of the SARS-CoV-2 virus. Here, we describe an influenza virus-based vaccine for SARS-CoV-2. We incorporated a membrane-anchored form of the SARS-CoV-2 spike receptor binding domain (RBD) in place of the neuraminidase (NA) coding sequence in an influenza virus also possessing a mutation that reduces the affinity of hemagglutinin for its sialic acid receptor. The resulting ΔNA(RBD)-Flu virus can be generated by reverse genetics and grown to high titers in cell culture. A single-dose intranasal inoculation of mice with ΔNA(RBD)-Flu elicits serum neutralizing antibody titers against SAR-CoV-2 comparable to those observed in humans following natural infection (~1:200). Furthermore, ΔNA(RBD)-Flu itself causes no apparent disease in mice. It might be possible to produce a vaccine similar to ΔNA(RBD)-Flu at scale by leveraging existing platforms for the production of influenza vaccines. |
| first_indexed | 2024-03-10T16:33:06Z |
| format | Article |
| id | doaj.art-a81ba677af6b4bf286a8a79e248c7f43 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-10T16:33:06Z |
| publishDate | 2020-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-a81ba677af6b4bf286a8a79e248c7f432023-11-20T12:41:26ZengMDPI AGViruses1999-49152020-09-0112998710.3390/v12090987Attenuated Influenza Virions Expressing the SARS-CoV-2 Receptor-Binding Domain Induce Neutralizing Antibodies in MiceAndrea N. Loes0Lauren E. Gentles1Allison J. Greaney2Katharine H. D. Crawford3Jesse D. Bloom4Division of Basic Sciences and Computational Biology Program, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USADivision of Basic Sciences and Computational Biology Program, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USADivision of Basic Sciences and Computational Biology Program, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USADivision of Basic Sciences and Computational Biology Program, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USADivision of Basic Sciences and Computational Biology Program, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USAAn effective vaccine is essential for controlling the spread of the SARS-CoV-2 virus. Here, we describe an influenza virus-based vaccine for SARS-CoV-2. We incorporated a membrane-anchored form of the SARS-CoV-2 spike receptor binding domain (RBD) in place of the neuraminidase (NA) coding sequence in an influenza virus also possessing a mutation that reduces the affinity of hemagglutinin for its sialic acid receptor. The resulting ΔNA(RBD)-Flu virus can be generated by reverse genetics and grown to high titers in cell culture. A single-dose intranasal inoculation of mice with ΔNA(RBD)-Flu elicits serum neutralizing antibody titers against SAR-CoV-2 comparable to those observed in humans following natural infection (~1:200). Furthermore, ΔNA(RBD)-Flu itself causes no apparent disease in mice. It might be possible to produce a vaccine similar to ΔNA(RBD)-Flu at scale by leveraging existing platforms for the production of influenza vaccines.https://www.mdpi.com/1999-4915/12/9/987SARS-CoV-2influenzaintranasallive attenuated vaccinespikeRBD |
| spellingShingle | Andrea N. Loes Lauren E. Gentles Allison J. Greaney Katharine H. D. Crawford Jesse D. Bloom Attenuated Influenza Virions Expressing the SARS-CoV-2 Receptor-Binding Domain Induce Neutralizing Antibodies in Mice Viruses SARS-CoV-2 influenza intranasal live attenuated vaccine spike RBD |
| title | Attenuated Influenza Virions Expressing the SARS-CoV-2 Receptor-Binding Domain Induce Neutralizing Antibodies in Mice |
| title_full | Attenuated Influenza Virions Expressing the SARS-CoV-2 Receptor-Binding Domain Induce Neutralizing Antibodies in Mice |
| title_fullStr | Attenuated Influenza Virions Expressing the SARS-CoV-2 Receptor-Binding Domain Induce Neutralizing Antibodies in Mice |
| title_full_unstemmed | Attenuated Influenza Virions Expressing the SARS-CoV-2 Receptor-Binding Domain Induce Neutralizing Antibodies in Mice |
| title_short | Attenuated Influenza Virions Expressing the SARS-CoV-2 Receptor-Binding Domain Induce Neutralizing Antibodies in Mice |
| title_sort | attenuated influenza virions expressing the sars cov 2 receptor binding domain induce neutralizing antibodies in mice |
| topic | SARS-CoV-2 influenza intranasal live attenuated vaccine spike RBD |
| url | https://www.mdpi.com/1999-4915/12/9/987 |
| work_keys_str_mv | AT andreanloes attenuatedinfluenzavirionsexpressingthesarscov2receptorbindingdomaininduceneutralizingantibodiesinmice AT laurenegentles attenuatedinfluenzavirionsexpressingthesarscov2receptorbindingdomaininduceneutralizingantibodiesinmice AT allisonjgreaney attenuatedinfluenzavirionsexpressingthesarscov2receptorbindingdomaininduceneutralizingantibodiesinmice AT katharinehdcrawford attenuatedinfluenzavirionsexpressingthesarscov2receptorbindingdomaininduceneutralizingantibodiesinmice AT jessedbloom attenuatedinfluenzavirionsexpressingthesarscov2receptorbindingdomaininduceneutralizingantibodiesinmice |