A Multiagent Alphavirus DNA Vaccine Delivered by Intramuscular Electroporation Elicits Robust and Durable Virus-Specific Immune Responses in Mice and Rabbits and Completely Protects Mice against Lethal Venezuelan, Western, and Eastern Equine Encephalitis Virus Aerosol Challenges
There remains a need for vaccines that can safely and effectively protect against the biological threat agents Venezuelan (VEEV), western (WEEV), and eastern (EEEV) equine encephalitis virus. Previously, we demonstrated that a VEEV DNA vaccine that was optimized for increased antigen expression and...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2018-01-01
|
| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2018/8521060 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832564347025489920 |
|---|---|
| author | Lesley C. Dupuy Michelle J. Richards Brian D. Livingston Drew Hannaman Connie S. Schmaljohn |
| author_facet | Lesley C. Dupuy Michelle J. Richards Brian D. Livingston Drew Hannaman Connie S. Schmaljohn |
| author_sort | Lesley C. Dupuy |
| collection | DOAJ |
| description | There remains a need for vaccines that can safely and effectively protect against the biological threat agents Venezuelan (VEEV), western (WEEV), and eastern (EEEV) equine encephalitis virus. Previously, we demonstrated that a VEEV DNA vaccine that was optimized for increased antigen expression and delivered by intramuscular (IM) electroporation (EP) elicited robust and durable virus-specific antibody responses in multiple animal species and provided complete protection against VEEV aerosol challenge in mice and nonhuman primates. Here, we performed a comparative evaluation of the immunogenicity and protective efficacy of individual optimized VEEV, WEEV, and EEEV DNA vaccines with that of a 1 : 1 : 1 mixture of these vaccines, which we have termed the 3-EEV DNA vaccine, when delivered by IM EP. The individual DNA vaccines and the 3-EEV DNA vaccine elicited robust and durable virus-specific antibody responses in mice and rabbits and completely protected mice from homologous VEEV, WEEV, and EEEV aerosol challenges. Taken together, the results from these studies demonstrate that the individual VEEV, WEEV, and EEEV DNA vaccines and the 3-EEV DNA vaccine delivered by IM EP provide an effective means of eliciting protection against lethal encephalitic alphavirus infections in a murine model and represent viable next-generation vaccine candidates that warrant further development. |
| format | Article |
| id | doaj-art-925ec11409834b90acbcb9e23d69ea0f |
| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2018-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-925ec11409834b90acbcb9e23d69ea0f2025-02-03T01:11:14ZengWileyJournal of Immunology Research2314-88612314-71562018-01-01201810.1155/2018/85210608521060A Multiagent Alphavirus DNA Vaccine Delivered by Intramuscular Electroporation Elicits Robust and Durable Virus-Specific Immune Responses in Mice and Rabbits and Completely Protects Mice against Lethal Venezuelan, Western, and Eastern Equine Encephalitis Virus Aerosol ChallengesLesley C. Dupuy0Michelle J. Richards1Brian D. Livingston2Drew Hannaman3Connie S. Schmaljohn4United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702-5011, USAUnited States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702-5011, USAIchor Medical Systems, Inc., San Diego, CA 92121-3209, USAIchor Medical Systems, Inc., San Diego, CA 92121-3209, USAUnited States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702-5011, USAThere remains a need for vaccines that can safely and effectively protect against the biological threat agents Venezuelan (VEEV), western (WEEV), and eastern (EEEV) equine encephalitis virus. Previously, we demonstrated that a VEEV DNA vaccine that was optimized for increased antigen expression and delivered by intramuscular (IM) electroporation (EP) elicited robust and durable virus-specific antibody responses in multiple animal species and provided complete protection against VEEV aerosol challenge in mice and nonhuman primates. Here, we performed a comparative evaluation of the immunogenicity and protective efficacy of individual optimized VEEV, WEEV, and EEEV DNA vaccines with that of a 1 : 1 : 1 mixture of these vaccines, which we have termed the 3-EEV DNA vaccine, when delivered by IM EP. The individual DNA vaccines and the 3-EEV DNA vaccine elicited robust and durable virus-specific antibody responses in mice and rabbits and completely protected mice from homologous VEEV, WEEV, and EEEV aerosol challenges. Taken together, the results from these studies demonstrate that the individual VEEV, WEEV, and EEEV DNA vaccines and the 3-EEV DNA vaccine delivered by IM EP provide an effective means of eliciting protection against lethal encephalitic alphavirus infections in a murine model and represent viable next-generation vaccine candidates that warrant further development.http://dx.doi.org/10.1155/2018/8521060 |
| spellingShingle | Lesley C. Dupuy Michelle J. Richards Brian D. Livingston Drew Hannaman Connie S. Schmaljohn A Multiagent Alphavirus DNA Vaccine Delivered by Intramuscular Electroporation Elicits Robust and Durable Virus-Specific Immune Responses in Mice and Rabbits and Completely Protects Mice against Lethal Venezuelan, Western, and Eastern Equine Encephalitis Virus Aerosol Challenges Journal of Immunology Research |
| title | A Multiagent Alphavirus DNA Vaccine Delivered by Intramuscular Electroporation Elicits Robust and Durable Virus-Specific Immune Responses in Mice and Rabbits and Completely Protects Mice against Lethal Venezuelan, Western, and Eastern Equine Encephalitis Virus Aerosol Challenges |
| title_full | A Multiagent Alphavirus DNA Vaccine Delivered by Intramuscular Electroporation Elicits Robust and Durable Virus-Specific Immune Responses in Mice and Rabbits and Completely Protects Mice against Lethal Venezuelan, Western, and Eastern Equine Encephalitis Virus Aerosol Challenges |
| title_fullStr | A Multiagent Alphavirus DNA Vaccine Delivered by Intramuscular Electroporation Elicits Robust and Durable Virus-Specific Immune Responses in Mice and Rabbits and Completely Protects Mice against Lethal Venezuelan, Western, and Eastern Equine Encephalitis Virus Aerosol Challenges |
| title_full_unstemmed | A Multiagent Alphavirus DNA Vaccine Delivered by Intramuscular Electroporation Elicits Robust and Durable Virus-Specific Immune Responses in Mice and Rabbits and Completely Protects Mice against Lethal Venezuelan, Western, and Eastern Equine Encephalitis Virus Aerosol Challenges |
| title_short | A Multiagent Alphavirus DNA Vaccine Delivered by Intramuscular Electroporation Elicits Robust and Durable Virus-Specific Immune Responses in Mice and Rabbits and Completely Protects Mice against Lethal Venezuelan, Western, and Eastern Equine Encephalitis Virus Aerosol Challenges |
| title_sort | multiagent alphavirus dna vaccine delivered by intramuscular electroporation elicits robust and durable virus specific immune responses in mice and rabbits and completely protects mice against lethal venezuelan western and eastern equine encephalitis virus aerosol challenges |
| url | http://dx.doi.org/10.1155/2018/8521060 |
| work_keys_str_mv | AT lesleycdupuy amultiagentalphavirusdnavaccinedeliveredbyintramuscularelectroporationelicitsrobustanddurablevirusspecificimmuneresponsesinmiceandrabbitsandcompletelyprotectsmiceagainstlethalvenezuelanwesternandeasternequineencephalitisvirusaerosolchallenges AT michellejrichards amultiagentalphavirusdnavaccinedeliveredbyintramuscularelectroporationelicitsrobustanddurablevirusspecificimmuneresponsesinmiceandrabbitsandcompletelyprotectsmiceagainstlethalvenezuelanwesternandeasternequineencephalitisvirusaerosolchallenges AT briandlivingston amultiagentalphavirusdnavaccinedeliveredbyintramuscularelectroporationelicitsrobustanddurablevirusspecificimmuneresponsesinmiceandrabbitsandcompletelyprotectsmiceagainstlethalvenezuelanwesternandeasternequineencephalitisvirusaerosolchallenges AT drewhannaman amultiagentalphavirusdnavaccinedeliveredbyintramuscularelectroporationelicitsrobustanddurablevirusspecificimmuneresponsesinmiceandrabbitsandcompletelyprotectsmiceagainstlethalvenezuelanwesternandeasternequineencephalitisvirusaerosolchallenges AT conniesschmaljohn amultiagentalphavirusdnavaccinedeliveredbyintramuscularelectroporationelicitsrobustanddurablevirusspecificimmuneresponsesinmiceandrabbitsandcompletelyprotectsmiceagainstlethalvenezuelanwesternandeasternequineencephalitisvirusaerosolchallenges AT lesleycdupuy multiagentalphavirusdnavaccinedeliveredbyintramuscularelectroporationelicitsrobustanddurablevirusspecificimmuneresponsesinmiceandrabbitsandcompletelyprotectsmiceagainstlethalvenezuelanwesternandeasternequineencephalitisvirusaerosolchallenges AT michellejrichards multiagentalphavirusdnavaccinedeliveredbyintramuscularelectroporationelicitsrobustanddurablevirusspecificimmuneresponsesinmiceandrabbitsandcompletelyprotectsmiceagainstlethalvenezuelanwesternandeasternequineencephalitisvirusaerosolchallenges AT briandlivingston multiagentalphavirusdnavaccinedeliveredbyintramuscularelectroporationelicitsrobustanddurablevirusspecificimmuneresponsesinmiceandrabbitsandcompletelyprotectsmiceagainstlethalvenezuelanwesternandeasternequineencephalitisvirusaerosolchallenges AT drewhannaman multiagentalphavirusdnavaccinedeliveredbyintramuscularelectroporationelicitsrobustanddurablevirusspecificimmuneresponsesinmiceandrabbitsandcompletelyprotectsmiceagainstlethalvenezuelanwesternandeasternequineencephalitisvirusaerosolchallenges AT conniesschmaljohn multiagentalphavirusdnavaccinedeliveredbyintramuscularelectroporationelicitsrobustanddurablevirusspecificimmuneresponsesinmiceandrabbitsandcompletelyprotectsmiceagainstlethalvenezuelanwesternandeasternequineencephalitisvirusaerosolchallenges |