An alphavirus replicon-based vaccine expressing a stabilized Spike antigen induces protective immunity and prevents transmission of SARS-CoV-2 between cats
Abstract Early in the SARS-CoV-2 pandemic concerns were raised regarding infection of new animal hosts and the effect on viral epidemiology. Infection of other animals could be detrimental by causing clinical disease, allowing further mutations, and bares the risk for the establishment of a non-huma...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2021-10-01
|
| Series: | npj Vaccines |
| Online Access: | https://doi.org/10.1038/s41541-021-00390-9 |
| _version_ | 1797642697765289984 |
|---|---|
| author | Martijn A. Langereis Irina C. Albulescu Judith Stammen-Vogelzangs Morindy Lambregts Ken Stachura Suzan Miller Angela M. Bosco-Lauth Airn E. Hartwig Stephanie M. Porter Michelle Allen Mark Mogler Frank J. M. van Kuppeveld Berend-Jan Bosch Paul Vermeij Ad de Groof Richard A. Bowen Randy Davis Zach Xu Ian Tarpey |
| author_facet | Martijn A. Langereis Irina C. Albulescu Judith Stammen-Vogelzangs Morindy Lambregts Ken Stachura Suzan Miller Angela M. Bosco-Lauth Airn E. Hartwig Stephanie M. Porter Michelle Allen Mark Mogler Frank J. M. van Kuppeveld Berend-Jan Bosch Paul Vermeij Ad de Groof Richard A. Bowen Randy Davis Zach Xu Ian Tarpey |
| author_sort | Martijn A. Langereis |
| collection | DOAJ |
| description | Abstract Early in the SARS-CoV-2 pandemic concerns were raised regarding infection of new animal hosts and the effect on viral epidemiology. Infection of other animals could be detrimental by causing clinical disease, allowing further mutations, and bares the risk for the establishment of a non-human reservoir. Cats were the first reported animals susceptible to natural and experimental infection with SARS-CoV-2. Given the concerns these findings raised, and the close contact between humans and cats, we aimed to develop a vaccine candidate that could reduce SARS-CoV-2 infection and in addition to prevent spread among cats. Here we report that a Replicon Particle (RP) vaccine based on Venezuelan equine encephalitis virus, known to be safe and efficacious in a variety of animal species, could induce neutralizing antibody responses in guinea pigs and cats. The design of the SARS-CoV-2 spike immunogen was critical in developing a strong neutralizing antibody response. Vaccination of cats was able to induce high neutralizing antibody responses, effective also against the SARS-CoV-2 B.1.1.7 variant. Interestingly, in contrast to control animals, the infectious virus could not be detected in oropharyngeal or nasal swabs of vaccinated cats after SARS-CoV-2 challenge. Correspondingly, the challenged control cats spread the virus to in-contact cats whereas the vaccinated cats did not transmit the virus. The results show that the RP vaccine induces protective immunity preventing SARS-CoV-2 infection and transmission. These data suggest that this RP vaccine could be a multi-species vaccine useful to prevent infection and spread to and between animals should that approach be required. |
| first_indexed | 2024-03-11T14:04:01Z |
| format | Article |
| id | doaj.art-2bd6aea37d7f4738945054de61b418dd |
| institution | Directory Open Access Journal |
| issn | 2059-0105 |
| language | English |
| last_indexed | 2024-03-11T14:04:01Z |
| publishDate | 2021-10-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Vaccines |
| spelling | doaj.art-2bd6aea37d7f4738945054de61b418dd2023-11-02T02:54:11ZengNature Portfolionpj Vaccines2059-01052021-10-016111010.1038/s41541-021-00390-9An alphavirus replicon-based vaccine expressing a stabilized Spike antigen induces protective immunity and prevents transmission of SARS-CoV-2 between catsMartijn A. Langereis0Irina C. Albulescu1Judith Stammen-Vogelzangs2Morindy Lambregts3Ken Stachura4Suzan Miller5Angela M. Bosco-Lauth6Airn E. Hartwig7Stephanie M. Porter8Michelle Allen9Mark Mogler10Frank J. M. van Kuppeveld11Berend-Jan Bosch12Paul Vermeij13Ad de Groof14Richard A. Bowen15Randy Davis16Zach Xu17Ian Tarpey18MSD Animal HealthDivision of Infectious Diseases and Immunology, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht UniversityMSD Animal HealthMSD Animal HealthMerck Animal HealthMerck Animal HealthCollege of Veterinary Medicine and Biomedical Sciences, Colorado State UniversityCollege of Veterinary Medicine and Biomedical Sciences, Colorado State UniversityCollege of Veterinary Medicine and Biomedical Sciences, Colorado State UniversityMerck Animal HealthMerck Animal HealthDivision of Infectious Diseases and Immunology, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht UniversityDivision of Infectious Diseases and Immunology, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht UniversityMSD Animal HealthMSD Animal HealthCollege of Veterinary Medicine and Biomedical Sciences, Colorado State UniversityMerck Animal HealthMerck Animal HealthMSD Animal HealthAbstract Early in the SARS-CoV-2 pandemic concerns were raised regarding infection of new animal hosts and the effect on viral epidemiology. Infection of other animals could be detrimental by causing clinical disease, allowing further mutations, and bares the risk for the establishment of a non-human reservoir. Cats were the first reported animals susceptible to natural and experimental infection with SARS-CoV-2. Given the concerns these findings raised, and the close contact between humans and cats, we aimed to develop a vaccine candidate that could reduce SARS-CoV-2 infection and in addition to prevent spread among cats. Here we report that a Replicon Particle (RP) vaccine based on Venezuelan equine encephalitis virus, known to be safe and efficacious in a variety of animal species, could induce neutralizing antibody responses in guinea pigs and cats. The design of the SARS-CoV-2 spike immunogen was critical in developing a strong neutralizing antibody response. Vaccination of cats was able to induce high neutralizing antibody responses, effective also against the SARS-CoV-2 B.1.1.7 variant. Interestingly, in contrast to control animals, the infectious virus could not be detected in oropharyngeal or nasal swabs of vaccinated cats after SARS-CoV-2 challenge. Correspondingly, the challenged control cats spread the virus to in-contact cats whereas the vaccinated cats did not transmit the virus. The results show that the RP vaccine induces protective immunity preventing SARS-CoV-2 infection and transmission. These data suggest that this RP vaccine could be a multi-species vaccine useful to prevent infection and spread to and between animals should that approach be required.https://doi.org/10.1038/s41541-021-00390-9 |
| spellingShingle | Martijn A. Langereis Irina C. Albulescu Judith Stammen-Vogelzangs Morindy Lambregts Ken Stachura Suzan Miller Angela M. Bosco-Lauth Airn E. Hartwig Stephanie M. Porter Michelle Allen Mark Mogler Frank J. M. van Kuppeveld Berend-Jan Bosch Paul Vermeij Ad de Groof Richard A. Bowen Randy Davis Zach Xu Ian Tarpey An alphavirus replicon-based vaccine expressing a stabilized Spike antigen induces protective immunity and prevents transmission of SARS-CoV-2 between cats npj Vaccines |
| title | An alphavirus replicon-based vaccine expressing a stabilized Spike antigen induces protective immunity and prevents transmission of SARS-CoV-2 between cats |
| title_full | An alphavirus replicon-based vaccine expressing a stabilized Spike antigen induces protective immunity and prevents transmission of SARS-CoV-2 between cats |
| title_fullStr | An alphavirus replicon-based vaccine expressing a stabilized Spike antigen induces protective immunity and prevents transmission of SARS-CoV-2 between cats |
| title_full_unstemmed | An alphavirus replicon-based vaccine expressing a stabilized Spike antigen induces protective immunity and prevents transmission of SARS-CoV-2 between cats |
| title_short | An alphavirus replicon-based vaccine expressing a stabilized Spike antigen induces protective immunity and prevents transmission of SARS-CoV-2 between cats |
| title_sort | alphavirus replicon based vaccine expressing a stabilized spike antigen induces protective immunity and prevents transmission of sars cov 2 between cats |
| url | https://doi.org/10.1038/s41541-021-00390-9 |
| work_keys_str_mv | AT martijnalangereis analphavirusrepliconbasedvaccineexpressingastabilizedspikeantigeninducesprotectiveimmunityandpreventstransmissionofsarscov2betweencats AT irinacalbulescu analphavirusrepliconbasedvaccineexpressingastabilizedspikeantigeninducesprotectiveimmunityandpreventstransmissionofsarscov2betweencats AT judithstammenvogelzangs analphavirusrepliconbasedvaccineexpressingastabilizedspikeantigeninducesprotectiveimmunityandpreventstransmissionofsarscov2betweencats AT morindylambregts analphavirusrepliconbasedvaccineexpressingastabilizedspikeantigeninducesprotectiveimmunityandpreventstransmissionofsarscov2betweencats AT kenstachura analphavirusrepliconbasedvaccineexpressingastabilizedspikeantigeninducesprotectiveimmunityandpreventstransmissionofsarscov2betweencats AT suzanmiller analphavirusrepliconbasedvaccineexpressingastabilizedspikeantigeninducesprotectiveimmunityandpreventstransmissionofsarscov2betweencats AT angelamboscolauth analphavirusrepliconbasedvaccineexpressingastabilizedspikeantigeninducesprotectiveimmunityandpreventstransmissionofsarscov2betweencats AT airnehartwig analphavirusrepliconbasedvaccineexpressingastabilizedspikeantigeninducesprotectiveimmunityandpreventstransmissionofsarscov2betweencats AT stephaniemporter analphavirusrepliconbasedvaccineexpressingastabilizedspikeantigeninducesprotectiveimmunityandpreventstransmissionofsarscov2betweencats AT michelleallen analphavirusrepliconbasedvaccineexpressingastabilizedspikeantigeninducesprotectiveimmunityandpreventstransmissionofsarscov2betweencats AT markmogler analphavirusrepliconbasedvaccineexpressingastabilizedspikeantigeninducesprotectiveimmunityandpreventstransmissionofsarscov2betweencats AT frankjmvankuppeveld analphavirusrepliconbasedvaccineexpressingastabilizedspikeantigeninducesprotectiveimmunityandpreventstransmissionofsarscov2betweencats AT berendjanbosch analphavirusrepliconbasedvaccineexpressingastabilizedspikeantigeninducesprotectiveimmunityandpreventstransmissionofsarscov2betweencats AT paulvermeij analphavirusrepliconbasedvaccineexpressingastabilizedspikeantigeninducesprotectiveimmunityandpreventstransmissionofsarscov2betweencats AT addegroof analphavirusrepliconbasedvaccineexpressingastabilizedspikeantigeninducesprotectiveimmunityandpreventstransmissionofsarscov2betweencats AT richardabowen analphavirusrepliconbasedvaccineexpressingastabilizedspikeantigeninducesprotectiveimmunityandpreventstransmissionofsarscov2betweencats AT randydavis analphavirusrepliconbasedvaccineexpressingastabilizedspikeantigeninducesprotectiveimmunityandpreventstransmissionofsarscov2betweencats AT zachxu analphavirusrepliconbasedvaccineexpressingastabilizedspikeantigeninducesprotectiveimmunityandpreventstransmissionofsarscov2betweencats AT iantarpey analphavirusrepliconbasedvaccineexpressingastabilizedspikeantigeninducesprotectiveimmunityandpreventstransmissionofsarscov2betweencats AT martijnalangereis alphavirusrepliconbasedvaccineexpressingastabilizedspikeantigeninducesprotectiveimmunityandpreventstransmissionofsarscov2betweencats AT irinacalbulescu alphavirusrepliconbasedvaccineexpressingastabilizedspikeantigeninducesprotectiveimmunityandpreventstransmissionofsarscov2betweencats AT judithstammenvogelzangs alphavirusrepliconbasedvaccineexpressingastabilizedspikeantigeninducesprotectiveimmunityandpreventstransmissionofsarscov2betweencats AT morindylambregts alphavirusrepliconbasedvaccineexpressingastabilizedspikeantigeninducesprotectiveimmunityandpreventstransmissionofsarscov2betweencats AT kenstachura alphavirusrepliconbasedvaccineexpressingastabilizedspikeantigeninducesprotectiveimmunityandpreventstransmissionofsarscov2betweencats AT suzanmiller alphavirusrepliconbasedvaccineexpressingastabilizedspikeantigeninducesprotectiveimmunityandpreventstransmissionofsarscov2betweencats AT angelamboscolauth alphavirusrepliconbasedvaccineexpressingastabilizedspikeantigeninducesprotectiveimmunityandpreventstransmissionofsarscov2betweencats AT airnehartwig alphavirusrepliconbasedvaccineexpressingastabilizedspikeantigeninducesprotectiveimmunityandpreventstransmissionofsarscov2betweencats AT stephaniemporter alphavirusrepliconbasedvaccineexpressingastabilizedspikeantigeninducesprotectiveimmunityandpreventstransmissionofsarscov2betweencats AT michelleallen alphavirusrepliconbasedvaccineexpressingastabilizedspikeantigeninducesprotectiveimmunityandpreventstransmissionofsarscov2betweencats AT markmogler alphavirusrepliconbasedvaccineexpressingastabilizedspikeantigeninducesprotectiveimmunityandpreventstransmissionofsarscov2betweencats AT frankjmvankuppeveld alphavirusrepliconbasedvaccineexpressingastabilizedspikeantigeninducesprotectiveimmunityandpreventstransmissionofsarscov2betweencats AT berendjanbosch alphavirusrepliconbasedvaccineexpressingastabilizedspikeantigeninducesprotectiveimmunityandpreventstransmissionofsarscov2betweencats AT paulvermeij alphavirusrepliconbasedvaccineexpressingastabilizedspikeantigeninducesprotectiveimmunityandpreventstransmissionofsarscov2betweencats AT addegroof alphavirusrepliconbasedvaccineexpressingastabilizedspikeantigeninducesprotectiveimmunityandpreventstransmissionofsarscov2betweencats AT richardabowen alphavirusrepliconbasedvaccineexpressingastabilizedspikeantigeninducesprotectiveimmunityandpreventstransmissionofsarscov2betweencats AT randydavis alphavirusrepliconbasedvaccineexpressingastabilizedspikeantigeninducesprotectiveimmunityandpreventstransmissionofsarscov2betweencats AT zachxu alphavirusrepliconbasedvaccineexpressingastabilizedspikeantigeninducesprotectiveimmunityandpreventstransmissionofsarscov2betweencats AT iantarpey alphavirusrepliconbasedvaccineexpressingastabilizedspikeantigeninducesprotectiveimmunityandpreventstransmissionofsarscov2betweencats |